WikiVet English - User contributions [en]

T cell differentiation

2012-05-28T12:16:23Z

Rjfrancisrvc: /* Introduction */

[[Image:TH1-2.jpg|thumb|right|200px|TH1 and 2 selection is influenced by infection - B. Catchpole, RVC 2008]]
==Introduction==
[[T cells|T cells]] are long lived and are involved in '''cell mediated immunity'''. Functionally they are divided by the expression of CD4+ or CD8+ markers. CD4+ T helper cells recognise antigens bound to MHC II complexes and are involved with the control of intracellular and extracellular pathogens; they can interact with CD8+, NK and dendritic cells or with B cells. Cytotoxic CD8+ T cells recognise the MHC I complex and destroy infected or neoplastic cells.
 
 
Within the blood and lymphoid organs the majority of T cells are antigen-naive T cells; only a small proportion are memory T cells. Naive T cells have yet to encounter antigen and can only be activated by antigen that is presented by dendritic cells. After initial antigenic activation, naïve T-cells develop into an intermediate stage cell called the TH0 cell which can then be activated by any antigen-presenting cell, e.g. Dendritic cells, [[Macrophages|macrophages]] or [[B cells]].
 
 
The TH0 cells have the capacity to differentiate into TH1, TH2 cells and a very recently described subtype TH17 cells. The type of cell that develops depends on the antigen presenting cell type. [[Macrophages|Macrophages]] cause the TH0 cell to develop into a TH1 cell induced by IL-12 production following macrophage-antigen interaction. B cells cause the TH0 cell to develop into a TH2 cell induced by IL-10 production following B cell-antigen interaction. On antigenic stimulation the TH1 or TH2 cells become activated, undergo clonal expansion and secrete a range of different cytokines. The third most recently described subset, TH17, form in the presence of IL-6 and TGF-β which are produced in the prescence of infection, and by either of the Antigen Presenting Cells (APCs). The importance of CD4+ TH cells is very clear in immunity. An example of a disease that targets CD4+ T cells is the Human Immunodeficieny Viruses (HIV) and Simian Immunodeficieny Viruses (SIV) which, when the CD4+ T cells are overwhelmed, causes Advanced Immunodeficiency Syndrome (AIDS).
 
 
For any one cell the cytokine-secreting activation state is short-lived, lasting between 4 - 40 hours. After this time these cells either die or mature into the long-lived memory cells. The proliferation of [[T cells]] continues until the presentation of antigen ceases.

==Dendritic Cells==
[[Image:Lineages of dendritic cells.jpg|thumb|right|300px|Diagram showing the 2 Lineages of dendritic cells - Copyright Prof Dirk Werling DrMedVet PhD MRCVS]]
There are two different lineages of dendritic cells:
*From myeloid precursor cells
*From plasmacytoid precursor cells
Dendritic cells stimulate a primary T cell response; they migrate through tissues, track to T cell dependent areas of the [[Lymph Nodes - Anatomy & Physiology|lymph nodes]] and cluster with the T cells. Dendritic cells have unique capabilities to take up antigen by pathways involving phagocytosis, macropinocytosis and clathrin-coated pits. The cell-surface antigen phenotype distinguishes the dendritic cell from [[Monocytes]]/macrophages and [[B cells]]. Their main function is priming T helper cells. They produce cell signaling cytokine molecules known as [[Cytokines#Chemokines|chemokines]].

===Maturation signals===
*Exogenous
**Bacteria or their products (LPS, LTA, lipoproteins)
**Viruses or their products (dsRNA, G-RSV)
**Protozoa or their products
**Helminths (SEA, ES 62)
*Endogenous
**Inflammatory mediators (IL-1/TNFα, hsp, FcR)
**Immune cells (CD40L, CD47, FasL)
[[Image:Maturation of Dendritic Cells.jpg|thumb|right|300px|Maturation of Dendritic Cells - Copyright Prof Dirk Werling DrMedVet PhD MRCVS]]

===Antigen Presentation===
Circulating [[Monocytes|monocytes]] differentiate to form immature dendritic cells called '''Langerhans Cells'''

Langerhans cells sample the tissue fluid by endocytosis:
*Foreign organisms are internalised
* Within the dendritic cells, antigen is digested to peptides
* Some of the peptides formed bind to the cell’s [[MHC]] molecules

The Langerhans cells leave the epithelium and travel via the afferent lymph flow. They are now known as '''Veiled Cells'''. Veiled cells enter the paracortical region of the [[Lymph Nodes - Anatomy & Physiology|lymph node]] where they present antigen to the T cells. They are now known as '''Interdigitating Dendritic Cells'''.

==TH1 Cells==
[[Image:TH1-macrophage.jpg|thumb|right|200px|TH1 cells boost macrophage response - B. Catchpole, RVC 2008]]
TH1 cells help macrophages digest bacteria - the organisms are contained in cellular vesicles.

TH1 cells secrete a range of cytokines, including:
* '''IL-2''', which induces proliferation of both [[Helper_CD4%2B#Helper_CD4.2B|CD4+]] and [[Cytotoxic_CD8%2B#Cytotoxic_CD8.2B|CD8+ T-cells]]. This stimulation of T cell proliferation is the main function of the TH1 cell.
* '''Interferon gamma''' ('''IFNγ''') which activates tissue macrophages and is the principal effector mechanism in the defence against intracellular bacteria and parasites such as Mycobacteria, Brucella, Rickettsia Leishmania, Coccidia, and Babesia. IFNγ activates macrophages and stimulates them to produce enzymes triggering intracellular killing mechanisms - specifically:
#Superoxide dismutase and myeloperoxidase that produce H2O2 and trigger the "superoxide burst".
#Nitric oxide synthase which produces nitric oxide.

This is another example of the immune system working through the innate immune response, and this can even act to suppress antibody synthesis.

==TH2 Cells==
[[Image:TH2-Bcell.jpg|thumb|right|200px|TH2 cells incite increased antibody production - B. Catchpole, RVC 2008]]
TH2 cells help [[B cells]] produce antibody where the organism is present in tissue fluid. The TH2 population influences B cell activation, proliferation and immunoglobulin production. TH2 T cells also secrete a range of cytokines:
#'''IL-4''' which stimulates B cell growth and induces the heavy chain switch from [[Immunoglobulin M|IgM]] to [[Immunoglobulin G|IgG]] , [[Immunoglobulin A|IgA]] and [[Immunoglobulin E|IgE]], as well as proliferation of basophils and mast cells. IL-4 can inhibit some T cell responses.
#'''IL-5''' which activates B cells and stimulates a high rate of proliferation. IL-5 also promotes immunoglobulin synthesis and the proliferation and differentiation of eosinophils.
#'''IL-6''' also activates B cells, stimulates a high rate of proliferation and promotes immunoglobulin synthesis.

==Common Functions of TH1 and TH2 Cells==
Both TH1 and TH2 cells produce IL-3 and granulocyte-macrophage colony stimulating factor ([[Leukopoiesis|GM-CSF]]). These act to activate and induce proliferation of [[Neutrophils|neutrophils]] and [[Macrophages|macrophages]]. [[Neutrophils|Neutrophils]] are the major phagocytic cells in the blood and the principal cells in acute inflammatory lesions whose function is chiefly the body's defence against extracellular bacteria. One of the major biological functions therefore of the activation of either TH subset is '''cytokine-controlled reactive [[Haematopoiesis - Overview|haematopoiesis]]'''.

==TH17 Cells==
''Still under investigation''
 
The TH17 cells form when TH0 cells are challenged with IL-6 and TGF-β to produce a number of cytokines that enhance the innate immune response <ref>{{citation|initiallast = Korn|initialfirst = T|2last = Bettelli|2first = E|3last = Oukka|3first = M|finallast = Kuchroo|finalfirst = V.K|year = 2009|jtitle = IL-17 and Th17 Cells|jor = Annual Reviews of Immunology|vol = 27|range = 485-517}}</ref>. The [[Cytokines|cytokines]] produced enhance the extravasation and chemotaxis of [[Neutrophils|neutrophils]] to the site of infection, in the aim of combating extracellular bacteria. These cytokines include:
*IL-17
*IL-17F
*IL-6
*TNFα
*IL-21
*IL-22
*IL-23
Importantly they do not produce:
*IFNγ normally associated with TH1 cells
*IL-4 normally associated with TH2 cells

==Cytotoxic T-Cells==
Cytotoxic T cells kill virus infected cells where the organisms are contained in the cell cytoplasm. Viruses are obligate intracellular pathogens that use the host cell machinery for pathogen protein synthesis; viral peptides associate with MHC class I and are expressed on the cell surface. [[T_cells#Cytotoxic_CD8.2B|CD8+ cytotoxic T lymphocytes (CTL)]] recognise the antigen-MHC complex. Cytotoxic T-cells secrete a pattern of cytokines similar to that of TH1 cells:
*IFNγ but not IL-2. The IFNγ shifts the balance of the immune response in favour of TH1 cells and there is therefore an increased level of T-cell proliferation. The initiation of the immune response via CTL leads to the selective proliferation of CTL which enhances the main mechanism of killing virally-infected cells.

===Killing Mechanism===
The CTl killing mechanism is initiated by direct CTL-target cell contact.
* The cells involved bind by antigen/[[MHC]] class I-TcR interaction. This allows the CTL's intracellular granules to be localised at the area of contact - the granules contain most of the molecules responsible for cytotoxicity.
* Direct cell contact stimulates the release of the granule contents into the area of contact between the two cells. The granules contain two groups of cytotoxic molecules.
#'''Perforin''', which is structurally related to the [[Complement|complement]] component, C9 and forms pores in the cell membrane.
#'''Granzymes''', which are proteolytic enzymes that target cell nucleases and cause programmed cell death.

==T-Cell Activation==
T cells function only after recent activation by an antigen.
* CD4 binds MHC class II - [[T_cells#Helper_CD4.2B|CD4+ T-cells]] recognise antigen only in association with [[Major Histocompatability Complexes#MHC II|MHC class II]].
* CD8 binds MHC class I - [[T_cells#Cytotoxic_CD8.2B|CD8+ T-cells]] recognise antigen only in association with [[Major Histocompatability Complexes#MHC I|MHC class I]].
Activation of T cells requires two distinct signals:
* '''Signal 1''' is the interaction of the TcR with the antigenic peptide/[[Major Histocompatability Complexes|MHC]] complex on the antigen presenting cell.
*'''Signal 2''' is the interaction of CD28 on the T cells with its ligand, CD80, on the antigen-presenting cell (APC). APC expression of CD80 only occurs after the engagement of pattern recognition on Fc receptors or activation by the cytokines Interferon, IL-1β or TNFα.
Signal 2 only occurs after the recognition of DANGER.

===Activation Scenarios===
1. '''No signal 1''':
:T cell is not activated as there is no antigen.
2. '''Both signal 1 and signal 2'''
:T cell is activated into clonal expansion and produces cytokines or becomes cytotoxic.
3. '''Signal 1 but no signal 2'''
:T-cell is triggered into apoptosis and dies.
:This is the basis of "clonal deletion" and is a major mechanism of the development of tolerance. It ensures that T-cells do not react with self (non-dangerous) antigens.

===TCR Complex===
[[Image:TCR Complex.jpg|thumb|right|250px|TCR Complex - Copyright Prof Dirk Werling DrMedVet PhD MRCVS]]
The T cell Receptor, or TCR is always associated with CD3, forming what is referred to as the '''TCR complex'''. TCR is expressed on the surface of T cells in a noncovalent association with a complex of transmembrane polypeptides.

CD3 contains 3 distinct polypeptide chains that are expressed exclusively on T cells: γ, ε, and δ. These molecules are members of the Ig superfamily - the ε chain associates with both γ and δ - and they play a 'chaperone' role in transporting newly synthesized TCR molecules to the cell surface.
CD3 also contains 2 identical chains: ζ and 16 kDa, which are found on T cells, macrophages and NK cells. Mice also can have an ε (eta) form.

===Response to Activation===
The response of the T cells to obtaining Signals 1 and 2 is to express the receptor for the cytokine interleukin-2 (IL-2) and CD4+ T-cells secrete IL-2.
The final trigger for clonal expansion is the engagement of IL-2R with IL-2 from any activated CD4+ T-cell. IL-2 produced by a CD4+ cell may also stimulate clonal expansion of the CD4+ cell.

==T-Helper Cell Function==
[[Image:TH1-2.jpg|thumb|right|200px|TH1 and 2 selection is influenced by infection - B. Catchpole, RVC 2008]]
The function of T helper cells is to regulate the immune response. The cytokines they secrete exert their influence on other cell populations; most of the different effector cells of the immune system are affected by one or more of the cytokines secreted by TH cells.

TH cells secrete cytokines for only a short period after they have been activated; the range of cytokines that TH cells secrete after activation chiefly determines their function. Different T-helper cell subpopulations (TH1, TH2 and TH17 cells) secrete different sets of cytokines.

==References==
<references />
 
{{Jim Bee 2007}}
[[Category:Lymphocytes|E]]

[[Category:Adaptive Immune System|C]]

T cell differentiation

2012-05-28T12:15:56Z

Rjfrancisrvc: /* Introduction */

[[Image:TH1-2.jpg|thumb|right|200px|TH1 and 2 selection is influenced by infection - B. Catchpole, RVC 2008]]
==Introduction==
[[T cells|T cells]] are long lived and are involved in '''cell mediated immunity'''. Functionally they are divided by the expression of CD4+ or CD8+ markers. CD4+ T helper cells recognise antigens bound to MHC II complexes and are involved with the control of intracellular and extracellular pathogens; they can interact with CD8+, NK and dendritic cells or with B cells. Cytotoxic CD8+ T cells recognise the MHC I complex and destroy infected or neoplastic cells.

Within the blood and lymphoid organs the majority of T cells are antigen-naive T cells; only a small proportion are memory T cells. Naive T cells have yet to encounter antigen and can only be activated by antigen that is presented by dendritic cells. After initial antigenic activation, naïve T-cells develop into an intermediate stage cell called the TH0 cell which can then be activated by any antigen-presenting cell, e.g. Dendritic cells, [[Macrophages|macrophages]] or [[B cells]].

The TH0 cells have the capacity to differentiate into TH1, TH2 cells and a very recently described subtype TH17 cells. The type of cell that develops depends on the antigen presenting cell type. [[Macrophages|Macrophages]] cause the TH0 cell to develop into a TH1 cell induced by IL-12 production following macrophage-antigen interaction. B cells cause the TH0 cell to develop into a TH2 cell induced by IL-10 production following B cell-antigen interaction. On antigenic stimulation the TH1 or TH2 cells become activated, undergo clonal expansion and secrete a range of different cytokines. The third most recently described subset, TH17, form in the presence of IL-6 and TGF-β which are produced in the prescence of infection, and by either of the Antigen Presenting Cells (APCs). The importance of CD4+ TH cells is very clear in immunity. An example of a disease that targets CD4+ T cells is the Human Immunodeficieny Viruses (HIV) and Simian Immunodeficieny Viruses (SIV) which, when the CD4+ T cells are overwhelmed, causes Advanced Immunodeficiency Syndrome (AIDS).

For any one cell the cytokine-secreting activation state is short-lived, lasting between 4 - 40 hours. After this time these cells either die or mature into the long-lived memory cells. The proliferation of [[T cells]] continues until the presentation of antigen ceases.

==Dendritic Cells==
[[Image:Lineages of dendritic cells.jpg|thumb|right|300px|Diagram showing the 2 Lineages of dendritic cells - Copyright Prof Dirk Werling DrMedVet PhD MRCVS]]
There are two different lineages of dendritic cells:
*From myeloid precursor cells
*From plasmacytoid precursor cells
Dendritic cells stimulate a primary T cell response; they migrate through tissues, track to T cell dependent areas of the [[Lymph Nodes - Anatomy & Physiology|lymph nodes]] and cluster with the T cells. Dendritic cells have unique capabilities to take up antigen by pathways involving phagocytosis, macropinocytosis and clathrin-coated pits. The cell-surface antigen phenotype distinguishes the dendritic cell from [[Monocytes]]/macrophages and [[B cells]]. Their main function is priming T helper cells. They produce cell signaling cytokine molecules known as [[Cytokines#Chemokines|chemokines]].

===Maturation signals===
*Exogenous
**Bacteria or their products (LPS, LTA, lipoproteins)
**Viruses or their products (dsRNA, G-RSV)
**Protozoa or their products
**Helminths (SEA, ES 62)
*Endogenous
**Inflammatory mediators (IL-1/TNFα, hsp, FcR)
**Immune cells (CD40L, CD47, FasL)
[[Image:Maturation of Dendritic Cells.jpg|thumb|right|300px|Maturation of Dendritic Cells - Copyright Prof Dirk Werling DrMedVet PhD MRCVS]]

===Antigen Presentation===
Circulating [[Monocytes|monocytes]] differentiate to form immature dendritic cells called '''Langerhans Cells'''

Langerhans cells sample the tissue fluid by endocytosis:
*Foreign organisms are internalised
* Within the dendritic cells, antigen is digested to peptides
* Some of the peptides formed bind to the cell’s [[MHC]] molecules

The Langerhans cells leave the epithelium and travel via the afferent lymph flow. They are now known as '''Veiled Cells'''. Veiled cells enter the paracortical region of the [[Lymph Nodes - Anatomy & Physiology|lymph node]] where they present antigen to the T cells. They are now known as '''Interdigitating Dendritic Cells'''.

==TH1 Cells==
[[Image:TH1-macrophage.jpg|thumb|right|200px|TH1 cells boost macrophage response - B. Catchpole, RVC 2008]]
TH1 cells help macrophages digest bacteria - the organisms are contained in cellular vesicles.

TH1 cells secrete a range of cytokines, including:
* '''IL-2''', which induces proliferation of both [[Helper_CD4%2B#Helper_CD4.2B|CD4+]] and [[Cytotoxic_CD8%2B#Cytotoxic_CD8.2B|CD8+ T-cells]]. This stimulation of T cell proliferation is the main function of the TH1 cell.
* '''Interferon gamma''' ('''IFNγ''') which activates tissue macrophages and is the principal effector mechanism in the defence against intracellular bacteria and parasites such as Mycobacteria, Brucella, Rickettsia Leishmania, Coccidia, and Babesia. IFNγ activates macrophages and stimulates them to produce enzymes triggering intracellular killing mechanisms - specifically:
#Superoxide dismutase and myeloperoxidase that produce H2O2 and trigger the "superoxide burst".
#Nitric oxide synthase which produces nitric oxide.

This is another example of the immune system working through the innate immune response, and this can even act to suppress antibody synthesis.

==TH2 Cells==
[[Image:TH2-Bcell.jpg|thumb|right|200px|TH2 cells incite increased antibody production - B. Catchpole, RVC 2008]]
TH2 cells help [[B cells]] produce antibody where the organism is present in tissue fluid. The TH2 population influences B cell activation, proliferation and immunoglobulin production. TH2 T cells also secrete a range of cytokines:
#'''IL-4''' which stimulates B cell growth and induces the heavy chain switch from [[Immunoglobulin M|IgM]] to [[Immunoglobulin G|IgG]] , [[Immunoglobulin A|IgA]] and [[Immunoglobulin E|IgE]], as well as proliferation of basophils and mast cells. IL-4 can inhibit some T cell responses.
#'''IL-5''' which activates B cells and stimulates a high rate of proliferation. IL-5 also promotes immunoglobulin synthesis and the proliferation and differentiation of eosinophils.
#'''IL-6''' also activates B cells, stimulates a high rate of proliferation and promotes immunoglobulin synthesis.

==Common Functions of TH1 and TH2 Cells==
Both TH1 and TH2 cells produce IL-3 and granulocyte-macrophage colony stimulating factor ([[Leukopoiesis|GM-CSF]]). These act to activate and induce proliferation of [[Neutrophils|neutrophils]] and [[Macrophages|macrophages]]. [[Neutrophils|Neutrophils]] are the major phagocytic cells in the blood and the principal cells in acute inflammatory lesions whose function is chiefly the body's defence against extracellular bacteria. One of the major biological functions therefore of the activation of either TH subset is '''cytokine-controlled reactive [[Haematopoiesis - Overview|haematopoiesis]]'''.

==TH17 Cells==
''Still under investigation''
 
The TH17 cells form when TH0 cells are challenged with IL-6 and TGF-β to produce a number of cytokines that enhance the innate immune response <ref>{{citation|initiallast = Korn|initialfirst = T|2last = Bettelli|2first = E|3last = Oukka|3first = M|finallast = Kuchroo|finalfirst = V.K|year = 2009|jtitle = IL-17 and Th17 Cells|jor = Annual Reviews of Immunology|vol = 27|range = 485-517}}</ref>. The [[Cytokines|cytokines]] produced enhance the extravasation and chemotaxis of [[Neutrophils|neutrophils]] to the site of infection, in the aim of combating extracellular bacteria. These cytokines include:
*IL-17
*IL-17F
*IL-6
*TNFα
*IL-21
*IL-22
*IL-23
Importantly they do not produce:
*IFNγ normally associated with TH1 cells
*IL-4 normally associated with TH2 cells

==Cytotoxic T-Cells==
Cytotoxic T cells kill virus infected cells where the organisms are contained in the cell cytoplasm. Viruses are obligate intracellular pathogens that use the host cell machinery for pathogen protein synthesis; viral peptides associate with MHC class I and are expressed on the cell surface. [[T_cells#Cytotoxic_CD8.2B|CD8+ cytotoxic T lymphocytes (CTL)]] recognise the antigen-MHC complex. Cytotoxic T-cells secrete a pattern of cytokines similar to that of TH1 cells:
*IFNγ but not IL-2. The IFNγ shifts the balance of the immune response in favour of TH1 cells and there is therefore an increased level of T-cell proliferation. The initiation of the immune response via CTL leads to the selective proliferation of CTL which enhances the main mechanism of killing virally-infected cells.

===Killing Mechanism===
The CTl killing mechanism is initiated by direct CTL-target cell contact.
* The cells involved bind by antigen/[[MHC]] class I-TcR interaction. This allows the CTL's intracellular granules to be localised at the area of contact - the granules contain most of the molecules responsible for cytotoxicity.
* Direct cell contact stimulates the release of the granule contents into the area of contact between the two cells. The granules contain two groups of cytotoxic molecules.
#'''Perforin''', which is structurally related to the [[Complement|complement]] component, C9 and forms pores in the cell membrane.
#'''Granzymes''', which are proteolytic enzymes that target cell nucleases and cause programmed cell death.

==T-Cell Activation==
T cells function only after recent activation by an antigen.
* CD4 binds MHC class II - [[T_cells#Helper_CD4.2B|CD4+ T-cells]] recognise antigen only in association with [[Major Histocompatability Complexes#MHC II|MHC class II]].
* CD8 binds MHC class I - [[T_cells#Cytotoxic_CD8.2B|CD8+ T-cells]] recognise antigen only in association with [[Major Histocompatability Complexes#MHC I|MHC class I]].
Activation of T cells requires two distinct signals:
* '''Signal 1''' is the interaction of the TcR with the antigenic peptide/[[Major Histocompatability Complexes|MHC]] complex on the antigen presenting cell.
*'''Signal 2''' is the interaction of CD28 on the T cells with its ligand, CD80, on the antigen-presenting cell (APC). APC expression of CD80 only occurs after the engagement of pattern recognition on Fc receptors or activation by the cytokines Interferon, IL-1β or TNFα.
Signal 2 only occurs after the recognition of DANGER.

===Activation Scenarios===
1. '''No signal 1''':
:T cell is not activated as there is no antigen.
2. '''Both signal 1 and signal 2'''
:T cell is activated into clonal expansion and produces cytokines or becomes cytotoxic.
3. '''Signal 1 but no signal 2'''
:T-cell is triggered into apoptosis and dies.
:This is the basis of "clonal deletion" and is a major mechanism of the development of tolerance. It ensures that T-cells do not react with self (non-dangerous) antigens.

===TCR Complex===
[[Image:TCR Complex.jpg|thumb|right|250px|TCR Complex - Copyright Prof Dirk Werling DrMedVet PhD MRCVS]]
The T cell Receptor, or TCR is always associated with CD3, forming what is referred to as the '''TCR complex'''. TCR is expressed on the surface of T cells in a noncovalent association with a complex of transmembrane polypeptides.

CD3 contains 3 distinct polypeptide chains that are expressed exclusively on T cells: γ, ε, and δ. These molecules are members of the Ig superfamily - the ε chain associates with both γ and δ - and they play a 'chaperone' role in transporting newly synthesized TCR molecules to the cell surface.
CD3 also contains 2 identical chains: ζ and 16 kDa, which are found on T cells, macrophages and NK cells. Mice also can have an ε (eta) form.

===Response to Activation===
The response of the T cells to obtaining Signals 1 and 2 is to express the receptor for the cytokine interleukin-2 (IL-2) and CD4+ T-cells secrete IL-2.
The final trigger for clonal expansion is the engagement of IL-2R with IL-2 from any activated CD4+ T-cell. IL-2 produced by a CD4+ cell may also stimulate clonal expansion of the CD4+ cell.

==T-Helper Cell Function==
[[Image:TH1-2.jpg|thumb|right|200px|TH1 and 2 selection is influenced by infection - B. Catchpole, RVC 2008]]
The function of T helper cells is to regulate the immune response. The cytokines they secrete exert their influence on other cell populations; most of the different effector cells of the immune system are affected by one or more of the cytokines secreted by TH cells.

TH cells secrete cytokines for only a short period after they have been activated; the range of cytokines that TH cells secrete after activation chiefly determines their function. Different T-helper cell subpopulations (TH1, TH2 and TH17 cells) secrete different sets of cytokines.

==References==
<references />
 
{{Jim Bee 2007}}
[[Category:Lymphocytes|E]]

[[Category:Adaptive Immune System|C]]

Immunity to Parasites

2012-05-28T12:04:30Z

Rjfrancisrvc: /* Adaptive Immunity */

==Innate Immunity==
[[File:Helminth Killing edit.png|300px|right|thumb|Helminth Killing - R.J.Francis, RVC 2012]]
[[File:Helmith Killing by Granulocytes.png|250px|right|thumb|Electron Micrograph of Helminth Killing by Granulocytes (G). Adapted from [[http://eprints.adm.unipi.it/527/]] - R.J.Francis, RVC 2012]]
The first line of defence against parasitic infection are the effector mechanisms of the innate immune system. The '''[[Macrophages|macrophages]]''' are important players in the defence against extracellular parasites. This is because macrophages are able to secrete [[Cytokines|cytokines]] as well as perform [[Phagocytosis|phagocytosis]]. In this they can act as 'killer cells' through antibody-dependent cell-mediated cytotoxicity, for example specific [[Immunoglobulins|IgG]]/[[Immunoglobulins|IgE]] enhances the ability of macrophages to kill schistosomules through the interaction of Fc receptors on the surface of the macrophage. Of the secreted cytokines, the secretion of TNFα is of particular importance. This is because TNFα activates other macrophages and can have toxic effects in high amounts. TNFα also renders hepatocytes resistant to malarial infection when in conjunction with IL-1. Cytokine secretion (in particular IFNγ) can also enhance killing by mechanisms using free radicals and O2-independent toxins (e.g. nitric oxide).
 
 
As well as the macrophages, the granulocytes form the main effector response to parasitic infection. '''[[Eosinophils|Eosinophils]]''' are very important in the destruction of larger parasites even though they are less phagocytic than [[Neutrophils|neutrophils]]. Most activity from eosinophils is controlled by antigen-specific mechanisms, for example binding to worms coated with [[IgG]]/[[IgE]] increases '''degranulation'''. Degranulation, through the process known as '''exocytosis''', releases enzymes that degrade the parasite into smaller chunks so it can be cleared by phagocytosis. The eosinophils also form the end point of the adaptive immune response to larger parasites with the killing of some larvae being enhanced by the activity of mast cells, for example antigens released by ''S. mansoni'' cause IgE-dependent degranulation of mast cells, the products of which selectively attract eosinophils. Mast cells and eosinophils degranulation enhances the TH2 response through the release of [[Cytokines|cytokines]], for example IL-4 and IL-13, that is needed to clear a stubborn infection.
 
 
The other granulocytes present in parasite-infected inflammatory lesions and involved in the anti-parasitic response are the '''[[Neutrophils|neutrophils]]'''. In the parasitic response they have similar properties to macrophages with activation caused by cytokines such as TNFα, IFNγ and GM-CSF. Their mechanism for killing is by an intense respiratory burst, with extracellular killing being mediated by hydrogen peroxide (H2O2). In addition, they also express Fc and [[Complement|complement]] receptors so can participate in antibody-dependent cell-mediated cytotoxicity and [[Phagocytosis|phagocytosis]]. Due to innate inflammatory mechanisms neutrophils are early responders to parasite infection.
 
 
'''[[Platelets|Platelets]]''' also form part of the innate immune response to parasites. Their main mode of action is the binding and release of granular contents, in particular inflammatory peptides. The cytotoxic activity of plateltes is increased by cytokines such as TNFα and IFNγ. The potential targets include the larval stage of flukes, e.g. ''T. gondii'', ''T. cruzi'' and ''S. Mansoni''. Like other effector cells, platelets express Fc receptors, making them able to perform antibody-dependent cytotoxicity.

==Adaptive Immunity==
Although the innate immune system provides an effective first line of defence, '''[[T cells|T cells]]''' are fundamental in the development of immunity, demonstrated using T-cell deprived mice that fail to resolve otherwise non-lethal infections of, for example, ''T. cruzi''.
*Both CD4+ and CD8+ cells are required for protection, e.g CD4+ cells protect against the blood stage of a Plasmodium infection (erythrocytes do not express MHC class I), while CD8+ cells are required to mediate immunity against the liver stage (hepatocytes do not express MHC class II).
*TH1 cells are required to fight intracellular protozoa - the release of IFNγ activates macrophages to kill the protozoa residing within them
*Helminth infections require both TH1 and TH2 responses, e.g. during ''S. mansoni'' the secretion of IFNγ by TH1 cells activates mechanisms that destroy larvae in the lungs, although the TH2 subset, secreting IL-5, predominate. IL-5 is responsible for the eosinophilia associated with parasite infections.
*TH2 cells are required for the destruction of intestinal worms, where they induce mucosal mast cells and interact with [[Eosinophils|eosinophils]]
While cell-mediated immunity is important in tissue infections, such as Leishmania, specific antibodies are important in controlling parasites that live in the bloodstream, e.g. malaria. Mechanisms of antibody-mediated immunity include:
*Directly damaging protozoa
*Activating [[Complement|complement]], and the subsequent Membrane Attack Complex
*Blocking attachment to host cells
*Enhancing macrophage [[Phagocytosis|phagocytosis]]
*Involvement in antibody-dependent cell-mediated cytotoxicity

=='''Immunopathology'''==
The immunopathology is the damage resulting from an immune response to the parasites. Examples include:
*The increase in macrophages and lymphocytes in the liver and spleen can lead to swelling of these organs, e.g. visceral leishmaniasis
*T-cell dependent (TH1 and TH17) granulomas forming in organs, e.g. schistosomiasis in the liver
*The pathology of elephantiasis is thought to be due to changes in the adult filariae in the lymphatic system
*Formation of immune complexes, e.g. deposition in the kidney during malarial infection
*Anaphylactic shock caused by [[IgE]] production, e.g. after the rupture of hydatid cysts
*Cross-reaction of antibodies with host tissue, e.g. ''O. volvulus'', the cause of river blindness, expresses an antigen similar to a protein in the retina
*Excessive production of cytokines, such as TNFα, may contribute to pathology of diseases such as malaria

=='''Evading immune defences'''==

Parasites can evade an immune response from the host by changing the antigens presented to the host, produce antigens that mimic the host's antigens and can produce down-regulating factors which suppress or modify the host's immune responses. Having a rapid turnover of their surface coat when host cells bind and by being able to live in sites which are protected from the host's immune response allow parasites to establish themselves in a particular species.
*Selection of innapropriate defences - by exploiting the 'adjuvant' mechanism, some parasites are able to activate the inappropriate helper T cell subset, e.g Leishmania
*Antigenic variation avoids recognition by antibody and complement, e.g. ''T. brucei''
*Inhibiting fusion of lysosomes
*Escaping into the cytoplasm, e.g. ''T. cruzi''
*Inhibiting respiratory burst, e.g. Leishmania
*Forming cysts in muscle tissue, e.g. ''T. spiralis'' - also develops decay accelerating factor (DAF)
*Production of antioxidants, e.g. ''W. bancrofti''

<big>'''Also see [[Adaptive Immunity to Parasites]]'''</big>

[[Category:Parasites]]

[[Category:To_Do_-_Blood]]

Adaptive Immunity Flashcards

2012-05-28T11:57:46Z

Rjfrancisrvc: /* Adaptive Immunity to Parasites */

===Actions and Tools of the Adaptive Immune System===
<FlashCard questions="6">
|q1=Complete the sentence:
T cell receptors recognise ??? fragments on the cell surface. B cell receptors recognise ??? in the ??? fluid.
|a1=
*antigen
*whole antigen
*extracellular
|l1=Adaptive Immune System - Overview#Antigen Recognition
|q2=Dendritic cells and macrophages are types of which kind of cells?
|a2=Antigen presenting cells (APCs)
|l2=Adaptive Immune System - Overview#Antigen Recognition
|q3=What can CD3+ T cells differentiate into?
|a3=
*CD4+ Helper T cells
*CD8+ Cytotoxic T cells
|l3=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q4=What is the main function of T helper I (TH1) cells?
|a4=Enhancing the macrophage response
|l4=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q5=What is the main function of T helper II (TH2) cells?
|a5=Enhancing the B cell antibody production
|l5=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q6=Name 3 types of antigen binding molecules
|a6=
*Immunolglobulins
*T cell receptors (TCRs)
*Natural Killer cells (NK cells)
|l6=Adaptive Immune System - Overview#Antigen Binding Molecules
</FlashCard>

===Adaptive Immunity to Viruses===
<FlashCard questions="3">
|q1=Which humoral factors are used against viruses in the adaptive response?
|a1=
*Production of neutralising antibody
*Antibody-dependent cell mediated cytotoxicity (ADCC)
|l1=Adaptive Immunity to Viruses
|q2=What is the cell mediated adaptive response against viruses?
|a2=CD8+ T-cell mediated killing of virus infected cells
|l2=Adaptive Immunity to Viruses
|q3=How are viral infected cells killed by apoptosis?
|a3=
*Perforin and granzymes released to activate the caspase cascade
*Fas-ligand triggers the Fas-mediated apoptosis pathway
*Cytotoxic cytokines act on TNF receptors to induce programmed cell death
|l3=Adaptive Immunity to Viruses
</FlashCard>

===Adaptive Immunity to Bacteria===
<FlashCard questions="4">
|q1=What is the humoral response to bacterial infection?
|a1=
*Complement activation of the classical pathway
*Production of IgM and IgG
|l1=Adaptive Immunity to Bacteria
|q2=What is the cell-mediated response to bacterial infection?
|a2=
*Help for macrophages
*Production of IgG
*T helper type I cell help
|l2=Adaptive Immunity to Bacteria
|q3=What is the response to an extracellular bacterial infection?
|a3=Complement and phagocytosis
*Production of IgM
*T helper type II and B cell production
*Class switching of IgM to IgG
|l3=Adaptive Immunity to Bacteria
|q4=What is the response to a vesicular bacterial infection?
|a4=
*IL-12 released from an infected macrophage
*T helper type I cells stimulated
*IFN-γ released triggering the macrophages to destroy the bacteria
|l4=Adaptive Immunity to Bacteria
</FlashCard>
===Adaptive Immunity to Parasites===
<FlashCard questions="2">
|q1=What is the humoral response to a parasitic worm (helminth) infection?
|a1=Production of IgE
|l1=Adaptive Immunity to Parasites
|q2=Which cells respond to the humoral response?
|a2=
*[[Eosinophils]]
*[[Basophils]]
*[[Mast Cells]]
|l2=Adaptive Immunity to Parasites
</FlashCard>

 
{{Jim Bee 2007}}
[[Category:Immunology Flashcards]]
[[Category:Adaptive Immune System|Z]]

Adaptive Immunity Flashcards

2012-05-28T11:57:28Z

Rjfrancisrvc: /* Adaptive Immunity to Parasites */

===Actions and Tools of the Adaptive Immune System===
<FlashCard questions="6">
|q1=Complete the sentence:
T cell receptors recognise ??? fragments on the cell surface. B cell receptors recognise ??? in the ??? fluid.
|a1=
*antigen
*whole antigen
*extracellular
|l1=Adaptive Immune System - Overview#Antigen Recognition
|q2=Dendritic cells and macrophages are types of which kind of cells?
|a2=Antigen presenting cells (APCs)
|l2=Adaptive Immune System - Overview#Antigen Recognition
|q3=What can CD3+ T cells differentiate into?
|a3=
*CD4+ Helper T cells
*CD8+ Cytotoxic T cells
|l3=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q4=What is the main function of T helper I (TH1) cells?
|a4=Enhancing the macrophage response
|l4=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q5=What is the main function of T helper II (TH2) cells?
|a5=Enhancing the B cell antibody production
|l5=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q6=Name 3 types of antigen binding molecules
|a6=
*Immunolglobulins
*T cell receptors (TCRs)
*Natural Killer cells (NK cells)
|l6=Adaptive Immune System - Overview#Antigen Binding Molecules
</FlashCard>

===Adaptive Immunity to Viruses===
<FlashCard questions="3">
|q1=Which humoral factors are used against viruses in the adaptive response?
|a1=
*Production of neutralising antibody
*Antibody-dependent cell mediated cytotoxicity (ADCC)
|l1=Adaptive Immunity to Viruses
|q2=What is the cell mediated adaptive response against viruses?
|a2=CD8+ T-cell mediated killing of virus infected cells
|l2=Adaptive Immunity to Viruses
|q3=How are viral infected cells killed by apoptosis?
|a3=
*Perforin and granzymes released to activate the caspase cascade
*Fas-ligand triggers the Fas-mediated apoptosis pathway
*Cytotoxic cytokines act on TNF receptors to induce programmed cell death
|l3=Adaptive Immunity to Viruses
</FlashCard>

===Adaptive Immunity to Bacteria===
<FlashCard questions="4">
|q1=What is the humoral response to bacterial infection?
|a1=
*Complement activation of the classical pathway
*Production of IgM and IgG
|l1=Adaptive Immunity to Bacteria
|q2=What is the cell-mediated response to bacterial infection?
|a2=
*Help for macrophages
*Production of IgG
*T helper type I cell help
|l2=Adaptive Immunity to Bacteria
|q3=What is the response to an extracellular bacterial infection?
|a3=Complement and phagocytosis
*Production of IgM
*T helper type II and B cell production
*Class switching of IgM to IgG
|l3=Adaptive Immunity to Bacteria
|q4=What is the response to a vesicular bacterial infection?
|a4=
*IL-12 released from an infected macrophage
*T helper type I cells stimulated
*IFN-γ released triggering the macrophages to destroy the bacteria
|l4=Adaptive Immunity to Bacteria
</FlashCard>
===Adaptive Immunity to Parasites===
<FlashCard questions="2">
|q1=What is the humoral response to a parasitic worm (helminth) infection?
|a1=Production of IgE
|l1=Adaptive Immunity to Parasites
|q2=Which cells respond to the humoral response?
|a2=
*[[Eosinophils]]
*[[Basophils]]
*[[Mast cells]]
|l2=Adaptive Immunity to Parasites
</FlashCard>

 
{{Jim Bee 2007}}
[[Category:Immunology Flashcards]]
[[Category:Adaptive Immune System|Z]]

Basophils

2012-05-28T11:56:28Z

Rjfrancisrvc: /* Interactions */

[[Image:LH Basophil Histology.jpg|thumb|right|150px|Basophil©RVC 2008]] [[Image:LH Avian Basophil Histology.jpg|thumb|right|150px|Avian Basophil©RVC 2008]]

== Introduction ==

Basophils are derived from the same stem cell line as [[Mast Cells|mast cells]] and while they are similar to mast cells, they are not identical (they are thought by some to be immature mast cells). They are the least common of all the [[Leukocytes|leukocytes]], are a similar size to neutrophils and eosinophils and are characterised by the large number of basophilic staining granules in their cytoplasm. They are present in the circulation but rarely found in tissue.

== Development ==

The basophil is a [[Blood Cells - Overview|granulocyte]] and has a similar development to the other granulocytes. This process is called [[Leukopoiesis#Granulopoiesis|granulopoiesis]].

== Granules ==

Two types of granules are present in basophils:

*Azurophilic granules which are present in all granulocytes and contain acid hydrolases and other enzymes.
*Specific granules contain heparin, histamine, leukotrienes and some lysosomes. Heparin has anti-coagulative capabilities and is also involved in assisting lipid uptake from the blood after meals. Histamine causes vasodilation.

 

== Actions ==

Fc receptors on the basophil surface binds with IgE formed during allergic reactions and causes them to degranulate. The vasoactive substances released from the granules causes vasodilation allowing for the infiltration of other leukocytes i.e. [[Neutrophils#Movement|neutrophil diapedesis]].

=== Role in pathology ===

*Classically a cell involved in [[Acute Inflammation|acute inflammation]]

== Interactions ==

*[[IgE]] and CD40 receptors on the basophils interact with B cells to increase [[IgE]] production
*IL-8 released by [[Neutrophils|neutrophils]] attracts basophils
*[[Complement]] factor C3a binds to the basophil and causes degranulation

 

[[Category:Blood_Cells]] [[Category:Kate_English_reviewing]]

Adaptive Immunity Flashcards

2012-05-28T11:55:48Z

Rjfrancisrvc: /* Adaptive Immunity to Parasites */

===Actions and Tools of the Adaptive Immune System===
<FlashCard questions="6">
|q1=Complete the sentence:
T cell receptors recognise ??? fragments on the cell surface. B cell receptors recognise ??? in the ??? fluid.
|a1=
*antigen
*whole antigen
*extracellular
|l1=Adaptive Immune System - Overview#Antigen Recognition
|q2=Dendritic cells and macrophages are types of which kind of cells?
|a2=Antigen presenting cells (APCs)
|l2=Adaptive Immune System - Overview#Antigen Recognition
|q3=What can CD3+ T cells differentiate into?
|a3=
*CD4+ Helper T cells
*CD8+ Cytotoxic T cells
|l3=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q4=What is the main function of T helper I (TH1) cells?
|a4=Enhancing the macrophage response
|l4=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q5=What is the main function of T helper II (TH2) cells?
|a5=Enhancing the B cell antibody production
|l5=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q6=Name 3 types of antigen binding molecules
|a6=
*Immunolglobulins
*T cell receptors (TCRs)
*Natural Killer cells (NK cells)
|l6=Adaptive Immune System - Overview#Antigen Binding Molecules
</FlashCard>

===Adaptive Immunity to Viruses===
<FlashCard questions="3">
|q1=Which humoral factors are used against viruses in the adaptive response?
|a1=
*Production of neutralising antibody
*Antibody-dependent cell mediated cytotoxicity (ADCC)
|l1=Adaptive Immunity to Viruses
|q2=What is the cell mediated adaptive response against viruses?
|a2=CD8+ T-cell mediated killing of virus infected cells
|l2=Adaptive Immunity to Viruses
|q3=How are viral infected cells killed by apoptosis?
|a3=
*Perforin and granzymes released to activate the caspase cascade
*Fas-ligand triggers the Fas-mediated apoptosis pathway
*Cytotoxic cytokines act on TNF receptors to induce programmed cell death
|l3=Adaptive Immunity to Viruses
</FlashCard>

===Adaptive Immunity to Bacteria===
<FlashCard questions="4">
|q1=What is the humoral response to bacterial infection?
|a1=
*Complement activation of the classical pathway
*Production of IgM and IgG
|l1=Adaptive Immunity to Bacteria
|q2=What is the cell-mediated response to bacterial infection?
|a2=
*Help for macrophages
*Production of IgG
*T helper type I cell help
|l2=Adaptive Immunity to Bacteria
|q3=What is the response to an extracellular bacterial infection?
|a3=Complement and phagocytosis
*Production of IgM
*T helper type II and B cell production
*Class switching of IgM to IgG
|l3=Adaptive Immunity to Bacteria
|q4=What is the response to a vesicular bacterial infection?
|a4=
*IL-12 released from an infected macrophage
*T helper type I cells stimulated
*IFN-γ released triggering the macrophages to destroy the bacteria
|l4=Adaptive Immunity to Bacteria
</FlashCard>
===Adaptive Immunity to Parasites===
<FlashCard questions="2">
|q1=What is the humoral response to a parasitic worm (helminth) infection?
|a1=Production of IgE
|l1=Adaptive Immunity to Parasites
|q2=Which cells respond to the humoral response?
|a2=
*[[Eosinophils]]
*[[Basophils/Mast cells]]
|l2=Adaptive Immunity to Parasites
</FlashCard>

 
{{Jim Bee 2007}}
[[Category:Immunology Flashcards]]
[[Category:Adaptive Immune System|Z]]

Adaptive Immunity Flashcards

2012-05-28T11:53:04Z

Rjfrancisrvc: /* Adaptive Immunity to Parasites */

===Actions and Tools of the Adaptive Immune System===
<FlashCard questions="6">
|q1=Complete the sentence:
T cell receptors recognise ??? fragments on the cell surface. B cell receptors recognise ??? in the ??? fluid.
|a1=
*antigen
*whole antigen
*extracellular
|l1=Adaptive Immune System - Overview#Antigen Recognition
|q2=Dendritic cells and macrophages are types of which kind of cells?
|a2=Antigen presenting cells (APCs)
|l2=Adaptive Immune System - Overview#Antigen Recognition
|q3=What can CD3+ T cells differentiate into?
|a3=
*CD4+ Helper T cells
*CD8+ Cytotoxic T cells
|l3=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q4=What is the main function of T helper I (TH1) cells?
|a4=Enhancing the macrophage response
|l4=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q5=What is the main function of T helper II (TH2) cells?
|a5=Enhancing the B cell antibody production
|l5=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q6=Name 3 types of antigen binding molecules
|a6=
*Immunolglobulins
*T cell receptors (TCRs)
*Natural Killer cells (NK cells)
|l6=Adaptive Immune System - Overview#Antigen Binding Molecules
</FlashCard>

===Adaptive Immunity to Viruses===
<FlashCard questions="3">
|q1=Which humoral factors are used against viruses in the adaptive response?
|a1=
*Production of neutralising antibody
*Antibody-dependent cell mediated cytotoxicity (ADCC)
|l1=Adaptive Immunity to Viruses
|q2=What is the cell mediated adaptive response against viruses?
|a2=CD8+ T-cell mediated killing of virus infected cells
|l2=Adaptive Immunity to Viruses
|q3=How are viral infected cells killed by apoptosis?
|a3=
*Perforin and granzymes released to activate the caspase cascade
*Fas-ligand triggers the Fas-mediated apoptosis pathway
*Cytotoxic cytokines act on TNF receptors to induce programmed cell death
|l3=Adaptive Immunity to Viruses
</FlashCard>

===Adaptive Immunity to Bacteria===
<FlashCard questions="4">
|q1=What is the humoral response to bacterial infection?
|a1=
*Complement activation of the classical pathway
*Production of IgM and IgG
|l1=Adaptive Immunity to Bacteria
|q2=What is the cell-mediated response to bacterial infection?
|a2=
*Help for macrophages
*Production of IgG
*T helper type I cell help
|l2=Adaptive Immunity to Bacteria
|q3=What is the response to an extracellular bacterial infection?
|a3=Complement and phagocytosis
*Production of IgM
*T helper type II and B cell production
*Class switching of IgM to IgG
|l3=Adaptive Immunity to Bacteria
|q4=What is the response to a vesicular bacterial infection?
|a4=
*IL-12 released from an infected macrophage
*T helper type I cells stimulated
*IFN-γ released triggering the macrophages to destroy the bacteria
|l4=Adaptive Immunity to Bacteria
</FlashCard>
===Adaptive Immunity to Parasites===
<FlashCard questions="2">
|q1=What is the humoral response to a parasitic worm (helminth) infection?
|a1=Production of IgE
|l1=Adaptive Immunity to Parasites
|q2=Which cells respond to the humoral response?
|a2=
*Eosinophils
*Basophils/Mast cells
|l2=Adaptive Immunity to Parasites
</FlashCard>

 
{{Jim Bee 2007}}
[[Category:Immunology Flashcards]]
[[Category:Adaptive Immune System|Z]]

Adaptive Immunity Flashcards

2012-05-28T11:52:39Z

Rjfrancisrvc: /* Adaptive Immunity to Parasites */

===Actions and Tools of the Adaptive Immune System===
<FlashCard questions="6">
|q1=Complete the sentence:
T cell receptors recognise ??? fragments on the cell surface. B cell receptors recognise ??? in the ??? fluid.
|a1=
*antigen
*whole antigen
*extracellular
|l1=Adaptive Immune System - Overview#Antigen Recognition
|q2=Dendritic cells and macrophages are types of which kind of cells?
|a2=Antigen presenting cells (APCs)
|l2=Adaptive Immune System - Overview#Antigen Recognition
|q3=What can CD3+ T cells differentiate into?
|a3=
*CD4+ Helper T cells
*CD8+ Cytotoxic T cells
|l3=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q4=What is the main function of T helper I (TH1) cells?
|a4=Enhancing the macrophage response
|l4=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q5=What is the main function of T helper II (TH2) cells?
|a5=Enhancing the B cell antibody production
|l5=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q6=Name 3 types of antigen binding molecules
|a6=
*Immunolglobulins
*T cell receptors (TCRs)
*Natural Killer cells (NK cells)
|l6=Adaptive Immune System - Overview#Antigen Binding Molecules
</FlashCard>

===Adaptive Immunity to Viruses===
<FlashCard questions="3">
|q1=Which humoral factors are used against viruses in the adaptive response?
|a1=
*Production of neutralising antibody
*Antibody-dependent cell mediated cytotoxicity (ADCC)
|l1=Adaptive Immunity to Viruses
|q2=What is the cell mediated adaptive response against viruses?
|a2=CD8+ T-cell mediated killing of virus infected cells
|l2=Adaptive Immunity to Viruses
|q3=How are viral infected cells killed by apoptosis?
|a3=
*Perforin and granzymes released to activate the caspase cascade
*Fas-ligand triggers the Fas-mediated apoptosis pathway
*Cytotoxic cytokines act on TNF receptors to induce programmed cell death
|l3=Adaptive Immunity to Viruses
</FlashCard>

===Adaptive Immunity to Bacteria===
<FlashCard questions="4">
|q1=What is the humoral response to bacterial infection?
|a1=
*Complement activation of the classical pathway
*Production of IgM and IgG
|l1=Adaptive Immunity to Bacteria
|q2=What is the cell-mediated response to bacterial infection?
|a2=
*Help for macrophages
*Production of IgG
*T helper type I cell help
|l2=Adaptive Immunity to Bacteria
|q3=What is the response to an extracellular bacterial infection?
|a3=Complement and phagocytosis
*Production of IgM
*T helper type II and B cell production
*Class switching of IgM to IgG
|l3=Adaptive Immunity to Bacteria
|q4=What is the response to a vesicular bacterial infection?
|a4=
*IL-12 released from an infected macrophage
*T helper type I cells stimulated
*IFN-γ released triggering the macrophages to destroy the bacteria
|l4=Adaptive Immunity to Bacteria
</FlashCard>
===Adaptive Immunity to Parasites===
<FlashCard questions="2">
|q1=What is the humoral response to a parasitic worm (helminth) infection?
|a1=Production of IgE
|l1=Adaptive Immunity to Parasites
|q2=Which cells respond to the humoral response?
|a2=
*Eosinophils
*Basophils/Mast cells
|l2=Adaptive Immunity to Parasites

</FlashCard>

 
{{Jim Bee 2007}}
[[Category:Immunology Flashcards]]
[[Category:Adaptive Immune System|Z]]

Adaptive Immunity Flashcards

2012-05-28T11:50:11Z

Rjfrancisrvc:

===Actions and Tools of the Adaptive Immune System===
<FlashCard questions="6">
|q1=Complete the sentence:
T cell receptors recognise ??? fragments on the cell surface. B cell receptors recognise ??? in the ??? fluid.
|a1=
*antigen
*whole antigen
*extracellular
|l1=Adaptive Immune System - Overview#Antigen Recognition
|q2=Dendritic cells and macrophages are types of which kind of cells?
|a2=Antigen presenting cells (APCs)
|l2=Adaptive Immune System - Overview#Antigen Recognition
|q3=What can CD3+ T cells differentiate into?
|a3=
*CD4+ Helper T cells
*CD8+ Cytotoxic T cells
|l3=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q4=What is the main function of T helper I (TH1) cells?
|a4=Enhancing the macrophage response
|l4=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q5=What is the main function of T helper II (TH2) cells?
|a5=Enhancing the B cell antibody production
|l5=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q6=Name 3 types of antigen binding molecules
|a6=
*Immunolglobulins
*T cell receptors (TCRs)
*Natural Killer cells (NK cells)
|l6=Adaptive Immune System - Overview#Antigen Binding Molecules
</FlashCard>

===Adaptive Immunity to Viruses===
<FlashCard questions="3">
|q1=Which humoral factors are used against viruses in the adaptive response?
|a1=
*Production of neutralising antibody
*Antibody-dependent cell mediated cytotoxicity (ADCC)
|l1=Adaptive Immunity to Viruses
|q2=What is the cell mediated adaptive response against viruses?
|a2=CD8+ T-cell mediated killing of virus infected cells
|l2=Adaptive Immunity to Viruses
|q3=How are viral infected cells killed by apoptosis?
|a3=
*Perforin and granzymes released to activate the caspase cascade
*Fas-ligand triggers the Fas-mediated apoptosis pathway
*Cytotoxic cytokines act on TNF receptors to induce programmed cell death
|l3=Adaptive Immunity to Viruses
</FlashCard>

===Adaptive Immunity to Bacteria===
<FlashCard questions="4">
|q1=What is the humoral response to bacterial infection?
|a1=
*Complement activation of the classical pathway
*Production of IgM and IgG
|l1=Adaptive Immunity to Bacteria
|q2=What is the cell-mediated response to bacterial infection?
|a2=
*Help for macrophages
*Production of IgG
*T helper type I cell help
|l2=Adaptive Immunity to Bacteria
|q3=What is the response to an extracellular bacterial infection?
|a3=Complement and phagocytosis
*Production of IgM
*T helper type II and B cell production
*Class switching of IgM to IgG
|l3=Adaptive Immunity to Bacteria
|q4=What is the response to a vesicular bacterial infection?
|a4=
*IL-12 released from an infected macrophage
*T helper type I cells stimulated
*IFN-γ released triggering the macrophages to destroy the bacteria
|l4=Adaptive Immunity to Bacteria
</FlashCard>
===Adaptive Immunity to Parasites===
<FlashCard questions="1">
|q1=What is the humoral response to a parasitic worm (helminth) infection?
|a1=Production of IgE
|l1=Adaptive Immunity to Parasites
|q2=Which cells respond to the humoral response?
|a2=
*Eosinophils
*Basophils/Mast cells
|l2=Adaptive Immunity to Parasites

</FlashCard>

 
{{Jim Bee 2007}}
[[Category:Immunology Flashcards]]
[[Category:Adaptive Immune System|Z]]

Adaptive Immunity Flashcards

2012-05-28T11:48:54Z

Rjfrancisrvc:

===Actions and Tools of the Adaptive Immune System===
<FlashCard questions="6">
|q1=Complete the sentence:
T cell receptors recognise ??? fragments on the cell surface. B cell receptors recognise ??? in the ??? fluid.
|a1=
*antigen
*whole antigen
*extracellular
|l1=Adaptive Immune System - Overview#Antigen Recognition
|q2=Dendritic cells and macrophages are types of which kind of cells?
|a2=Antigen presenting cells (APCs)
|l2=Adaptive Immune System - Overview#Antigen Recognition
|q3=What can CD3+ T cells differentiate into?
|a3=
*CD4+ Helper T cells
*CD8+ Cytotoxic T cells
|l3=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q4=What is the main function of T helper I (TH1) cells?
|a4=Enhancing the macrophage response
|l4=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q5=What is the main function of T helper II (TH2) cells?
|a5=Enhancing the B cell antibody production
|l5=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q6=Name 3 types of antigen binding molecules
|a6=
*Immunolglobulins
*T cell receptors (TCRs)
*Natural Killer cells (NK cells)
|l6=Adaptive Immune System - Overview#Antigen Binding Molecules
</FlashCard>

===Adaptive Immunity to Viruses===
<FlashCard questions="3">
|q1=Which humoral factors are used against viruses in the adaptive response?
|a1=
*Production of neutralising antibody
*Antibody-dependent cell mediated cytotoxicity (ADCC)
|l1=Adaptive Immunity to Viruses
|q2=What is the cell mediated adaptive response against viruses?
|a2=CD8+ T-cell mediated killing of virus infected cells
|l2=Adaptive Immunity to Viruses
|q3=How are viral infected cells killed by apoptosis?
|a3=
*Perforin and granzymes released to activate the caspase cascade
*Fas-ligand triggers the Fas-mediated apoptosis pathway
*Cytotoxic cytokines act on TNF receptors to induce programmed cell death
|l3=Adaptive Immunity to Viruses
</FlashCard>

===Adaptive Immunity to Bacteria===
<FlashCard questions="4">
|q1=What is the humoral response to bacterial infection?
|a1=
*Complement activation of the classical pathway
*Production of IgM and IgG
|l1=Adaptive Immunity to Bacteria
|q2=What is the cell-mediated response to bacterial infection?
|a2=
*Help for macrophages
*Production of IgG
*T helper type I cell help
|l2=Adaptive Immunity to Bacteria
|q3=What is the response to an extracellular bacterial infection?
|a3=Complement and phagocytosis
*Production of IgM
*T helper type II and B cell production
*Class switching of IgM to IgG
|l3=Adaptive Immunity to Bacteria
|q4=What is the response to a vesicular bacterial infection?
|a4=
*IL-12 released from an infected macrophage
*T helper type I cells stimulated
*IFN-γ released triggering the macrophages to destroy the bacteria
|l4=Adaptive Immunity to Bacteria
</FlashCard>
===Adaptive Immunity to Parasites===
<FlashCard questions="1">
|q1=What is the humoral response to a parasitic worm (helminth) infection?
|a1=Production of IgE
|l1=Adaptive Immunity to Parasites
|q2=Which cells respond to the humoral response?
|a2=
*Eosinophils
*Basophils/Mast cells
|l2=Adaptive Immunity to Parasites
</FlashCard>

 
{{Jim Bee 2007}}
[[Category:Immunology Flashcards]]
[[Category:Adaptive Immune System|Z]]

Adaptive Immunity Flashcards

2012-05-28T11:48:14Z

Rjfrancisrvc: /* Adaptive Immunity to Parasites */

===Actions and Tools of the Adaptive Immune System===
<FlashCard questions="6">
|q1=Complete the sentence:
T cell receptors recognise ??? fragments on the cell surface. B cell receptors recognise ??? in the ??? fluid.
|a1=
*antigen
*whole antigen
*extracellular
|l1=Adaptive Immune System - Overview#Antigen Recognition
|q2=Dendritic cells and macrophages are types of which kind of cells?
|a2=Antigen presenting cells (APCs)
|l2=Adaptive Immune System - Overview#Antigen Recognition
|q3=What can CD3+ T cells differentiate into?
|a3=
*CD4+ Helper T cells
*CD8+ Cytotoxic T cells
|l3=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q4=What is the main function of T helper I (TH1) cells?
|a4=Enhancing the macrophage response
|l4=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q5=What is the main function of T helper II (TH2) cells?
|a5=Enhancing the B cell antibody production
|l5=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q6=Name 3 types of antigen binding molecules
|a6=
*Immunolglobulins
*T cell receptors (TCRs)
*Natural Killer cells (NK cells)
|l6=Adaptive Immune System - Overview#Antigen Binding Molecules
</FlashCard>

===Adaptive Immunity to Viruses===
<FlashCard questions="3">
|q1=Which humoral factors are used against viruses in the adaptive response?
|a1=
*Production of neutralising antibody
*Antibody-dependent cell mediated cytotoxicity (ADCC)
|l1=Adaptive Immunity to Viruses
|q2=What is the cell mediated adaptive response against viruses?
|a2=CD8+ T-cell mediated killing of virus infected cells
|l2=Adaptive Immunity to Viruses
|q3=How are viral infected cells killed by apoptosis?
|a3=
*Perforin and granzymes released to activate the caspase cascade
*Fas-ligand triggers the Fas-mediated apoptosis pathway
*Cytotoxic cytokines act on TNF receptors to induce programmed cell death
|l3=Adaptive Immunity to Viruses
</FlashCard>

===Adaptive Immunity to Bacteria===
<FlashCard questions="4">
|q1=What is the humoral response to bacterial infection?
|a1=
*Complement activation of the classical pathway
*Production of IgM and IgG
|l1=Adaptive Immunity to Bacteria
|q2=What is the cell-mediated response to bacterial infection?
|a2=
*Help for macrophages
*Production of IgG
*T helper type I cell help
|l2=Adaptive Immunity to Bacteria
|q3=What is the response to an extracellular bacterial infection?
|a3=Complement and phagocytosis
*Production of IgM
*T helper type II and B cell production
*Class switching of IgM to IgG
|l3=Adaptive Immunity to Bacteria
|q4=What is the response to a vesicular bacterial infection?
|a4=
*IL-12 released from an infected macrophage
*T helper type I cells stimulated
*IFN-γ released triggering the macrophages to destroy the bacteria
|l4=Adaptive Immunity to Bacteria
</FlashCard>
===Adaptive Immunity to Parasites===
<FlashCard questions="1">
|q1=What is the humoral response to a parasitic worm (helminth) infection?
|a1=Production of IgE
|l1=Adaptive Immunity to Parasites
|q2=Which cells respond to the humoral response?
|a2=
*[[Eosinophils]]
*[[Basophils/Mast cells]]
|l2=Adaptive Immunity to Parasites
</FlashCard>

 
{{Jim Bee 2007}}
[[Category:Immunology Flashcards]]
[[Category:Adaptive Immune System|Z]]

Adaptive Immunity Flashcards

2012-05-28T11:47:43Z

Rjfrancisrvc:

===Actions and Tools of the Adaptive Immune System===
<FlashCard questions="6">
|q1=Complete the sentence:
T cell receptors recognise ??? fragments on the cell surface. B cell receptors recognise ??? in the ??? fluid.
|a1=
*antigen
*whole antigen
*extracellular
|l1=Adaptive Immune System - Overview#Antigen Recognition
|q2=Dendritic cells and macrophages are types of which kind of cells?
|a2=Antigen presenting cells (APCs)
|l2=Adaptive Immune System - Overview#Antigen Recognition
|q3=What can CD3+ T cells differentiate into?
|a3=
*CD4+ Helper T cells
*CD8+ Cytotoxic T cells
|l3=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q4=What is the main function of T helper I (TH1) cells?
|a4=Enhancing the macrophage response
|l4=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q5=What is the main function of T helper II (TH2) cells?
|a5=Enhancing the B cell antibody production
|l5=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q6=Name 3 types of antigen binding molecules
|a6=
*Immunolglobulins
*T cell receptors (TCRs)
*Natural Killer cells (NK cells)
|l6=Adaptive Immune System - Overview#Antigen Binding Molecules
</FlashCard>

===Adaptive Immunity to Viruses===
<FlashCard questions="3">
|q1=Which humoral factors are used against viruses in the adaptive response?
|a1=
*Production of neutralising antibody
*Antibody-dependent cell mediated cytotoxicity (ADCC)
|l1=Adaptive Immunity to Viruses
|q2=What is the cell mediated adaptive response against viruses?
|a2=CD8+ T-cell mediated killing of virus infected cells
|l2=Adaptive Immunity to Viruses
|q3=How are viral infected cells killed by apoptosis?
|a3=
*Perforin and granzymes released to activate the caspase cascade
*Fas-ligand triggers the Fas-mediated apoptosis pathway
*Cytotoxic cytokines act on TNF receptors to induce programmed cell death
|l3=Adaptive Immunity to Viruses
</FlashCard>

===Adaptive Immunity to Bacteria===
<FlashCard questions="4">
|q1=What is the humoral response to bacterial infection?
|a1=
*Complement activation of the classical pathway
*Production of IgM and IgG
|l1=Adaptive Immunity to Bacteria
|q2=What is the cell-mediated response to bacterial infection?
|a2=
*Help for macrophages
*Production of IgG
*T helper type I cell help
|l2=Adaptive Immunity to Bacteria
|q3=What is the response to an extracellular bacterial infection?
|a3=Complement and phagocytosis
*Production of IgM
*T helper type II and B cell production
*Class switching of IgM to IgG
|l3=Adaptive Immunity to Bacteria
|q4=What is the response to a vesicular bacterial infection?
|a4=
*IL-12 released from an infected macrophage
*T helper type I cells stimulated
*IFN-γ released triggering the macrophages to destroy the bacteria
|l4=Adaptive Immunity to Bacteria
</FlashCard>
===Adaptive Immunity to Parasites===
<FlashCard questions="1">
|q1=What is the humoral response to a parasitic worm (helminth) infection?
|a1=Production of IgE
|l1=Adaptive Immunity to Parasites
|q2=Which cells respond to the humoral response?
|a2=
*[[Eosinophils]]
*[[Basophils/Mast cells]]
|l1=Adaptive Immunity to Parasites
</FlashCard>

 
{{Jim Bee 2007}}
[[Category:Immunology Flashcards]]
[[Category:Adaptive Immune System|Z]]

Adaptive Immunity Flashcards

2012-05-28T11:45:01Z

Rjfrancisrvc: /* Adaptive Immunity to Parasites */

===Actions and Tools of the Adaptive Immune System===
<FlashCard questions="6">
|q1=Complete the sentence:
T cell receptors recognise ??? fragments on the cell surface. B cell receptors recognise ??? in the ??? fluid.
|a1=
*antigen
*whole antigen
*extracellular
|l1=Adaptive Immune System - Overview#Antigen Recognition
|q2=Dendritic cells and macrophages are types of which kind of cells?
|a2=Antigen presenting cells (APCs)
|l2=Adaptive Immune System - Overview#Antigen Recognition
|q3=What can CD3+ T cells differentiate into?
|a3=
*CD4+ Helper T cells
*CD8+ Cytotoxic T cells
|l3=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q4=What is the main function of T helper I (TH1) cells?
|a4=Enhancing the macrophage response
|l4=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q5=What is the main function of T helper II (TH2) cells?
|a5=Enhancing the B cell antibody production
|l5=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q6=Name 3 types of antigen binding molecules
|a6=
*Immunolglobulins
*T cell receptors (TCRs)
*Natural Killer cells (NK cells)
|l6=Adaptive Immune System - Overview#Antigen Binding Molecules
</FlashCard>

===Adaptive Immunity to Viruses===
<FlashCard questions="3">
|q1=Which humoral factors are used against viruses in the adaptive response?
|a1=
*Production of neutralising antibody
*Antibody-dependent cell mediated cytotoxicity (ADCC)
|l1=Adaptive Immunity to Viruses
|q2=What is the cell mediated adaptive response against viruses?
|a2=CD8+ T-cell mediated killing of virus infected cells
|l2=Adaptive Immunity to Viruses
|q3=How are viral infected cells killed by apoptosis?
|a3=
*Perforin and granzymes released to activate the caspase cascade
*Fas-ligand triggers the Fas-mediated apoptosis pathway
*Cytotoxic cytokines act on TNF receptors to induce programmed cell death
|l3=Adaptive Immunity to Viruses
</FlashCard>

===Adaptive Immunity to Bacteria===
<FlashCard questions="4">
|q1=What is the humoral response to bacterial infection?
|a1=
*Complement activation of the classical pathway
*Production of IgM and IgG
|l1=Adaptive Immunity to Bacteria
|q2=What is the cell-mediated response to bacterial infection?
|a2=
*Help for macrophages
*Production of IgG
*T helper type I cell help
|l2=Adaptive Immunity to Bacteria
|q3=What is the response to an extracellular bacterial infection?
|a3=Complement and phagocytosis
*Production of IgM
*T helper type II and B cell production
*Class switching of IgM to IgG
|l3=Adaptive Immunity to Bacteria
|q4=What is the response to a vesicular bacterial infection?
|a4=
*IL-12 released from an infected macrophage
*T helper type I cells stimulated
*IFN-γ released triggering the macrophages to destroy the bacteria
|l4=Adaptive Immunity to Bacteria
</FlashCard>
===Adaptive Immunity to Parasites===
<FlashCard questions="1">
|q1=What is the humoral response to a parasitic worm (helminth) infection?
|a1=Production of IgE
|l1=Adaptive Immunity to Parasites
</FlashCard>

 
{{Jim Bee 2007}}
[[Category:Immunology Flashcards]]
[[Category:Adaptive Immune System|Z]]

Adaptive Immunity to Parasites

2012-05-28T11:43:51Z

Rjfrancisrvc: /* Humoral */

==Overview==
The role of the adaptive immune system in parasitic infections is mainly to orchestrate the innate immune reactions to the parasites by producing a specific immune response. This could be done either through the cell-mediated response or through the humoral, antibody response. An important note is that the information given here is generalised as the response to each individual parasite is different as parasites themselves range from parasitc worms to malaria (for more information see the Parasitology section of WikiVet).

==Cell-Mediated==
Although the innate immune system provides an effective first line of defence, '''[[T cells|T cells]]''' are fundamental in the development of immunity, demonstrated using T-cell deprived mice that fail to resolve otherwise non-lethal infections of, for example, ''T. cruzi''.
*Both CD4+ T helper cells and CD8+ cytotoxic T cells are required for protection, e.g CD4+ cells protect against the blood stage of a Plasmodium infection (erythrocytes do not express [[Major Histocompatability Complexes|MHC]] class I), while CD8+ cells are required to mediate immunity against the liver stage (hepatocytes do not express [[Major Histocompatability Complexes|MHC]] class II).
*TH1 cells are required to fight intracellular protozoa - the release of Interferon-γ (IFNγ) activates macrophages to kill the protozoa residing within them
*Helminth infections require both TH1 and TH2 responses, e.g. during ''S. mansoni'' the secretion of IFNγ by TH1 cells activates mechanisms that destroy larvae in the lungs, although the TH2 subset, secreting Interleuken-5 (IL-5), predominate. IL-5 is the [[Cytokines|cytokine]] responsible for the eosinophilia associated with parasite infections.
*TH2 cells are required for the destruction of intestinal worms, where they induce mucosal mast cells and interact with [[Eosinophils|eosinophils]]

==Humoral==
While cell-mediated immunity is important in tissue infections, such as Leishmania, specific antibodies are important in controlling parasites that live in the bloodstream, e.g. malaria. Mechanisms of antibody-mediated immunity include:
*Directly damaging protozoa
*Activating [[Complement|complement]], and the subsequent Membrane Attack Complex
*Blocking attachment to host cells
*Enhancing macrophage phagocytosis
*Involvement in antibody-dependent cell-mediated cytotoxicity
The humoral response to parasitic worms involves the production of [[Immunoglobulin E|IgE]]. It is stimulated by [[Mast Cells|mast cells]] producing IL-4 ([[Innate Immune System|innate response]]) which causes isotype switching of [[Lymphocytes#B Cells|B cells]] to produce [[Immunoglobulin E|IgE]].

<big>'''Also see [[Immunity to Parasites]]'''</big>

 
{{Jim Bee 2007}}

[[Category:Adaptive Immune System]]

Adaptive Immunity Flashcards

2012-05-28T11:41:02Z

Rjfrancisrvc: /* Adaptive Immunity to Viruses */

===Actions and Tools of the Adaptive Immune System===
<FlashCard questions="6">
|q1=Complete the sentence:
T cell receptors recognise ??? fragments on the cell surface. B cell receptors recognise ??? in the ??? fluid.
|a1=
*antigen
*whole antigen
*extracellular
|l1=Adaptive Immune System - Overview#Antigen Recognition
|q2=Dendritic cells and macrophages are types of which kind of cells?
|a2=Antigen presenting cells (APCs)
|l2=Adaptive Immune System - Overview#Antigen Recognition
|q3=What can CD3+ T cells differentiate into?
|a3=
*CD4+ Helper T cells
*CD8+ Cytotoxic T cells
|l3=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q4=What is the main function of T helper I (TH1) cells?
|a4=Enhancing the macrophage response
|l4=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q5=What is the main function of T helper II (TH2) cells?
|a5=Enhancing the B cell antibody production
|l5=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q6=Name 3 types of antigen binding molecules
|a6=
*Immunolglobulins
*T cell receptors (TCRs)
*Natural Killer cells (NK cells)
|l6=Adaptive Immune System - Overview#Antigen Binding Molecules
</FlashCard>

===Adaptive Immunity to Viruses===
<FlashCard questions="3">
|q1=Which humoral factors are used against viruses in the adaptive response?
|a1=
*Production of neutralising antibody
*Antibody-dependent cell mediated cytotoxicity (ADCC)
|l1=Adaptive Immunity to Viruses
|q2=What is the cell mediated adaptive response against viruses?
|a2=CD8+ T-cell mediated killing of virus infected cells
|l2=Adaptive Immunity to Viruses
|q3=How are viral infected cells killed by apoptosis?
|a3=
*Perforin and granzymes released to activate the caspase cascade
*Fas-ligand triggers the Fas-mediated apoptosis pathway
*Cytotoxic cytokines act on TNF receptors to induce programmed cell death
|l3=Adaptive Immunity to Viruses
</FlashCard>

===Adaptive Immunity to Bacteria===
<FlashCard questions="4">
|q1=What is the humoral response to bacterial infection?
|a1=
*Complement activation of the classical pathway
*Production of IgM and IgG
|l1=Adaptive Immunity to Bacteria
|q2=What is the cell-mediated response to bacterial infection?
|a2=
*Help for macrophages
*Production of IgG
*T helper type I cell help
|l2=Adaptive Immunity to Bacteria
|q3=What is the response to an extracellular bacterial infection?
|a3=Complement and phagocytosis
*Production of IgM
*T helper type II and B cell production
*Class switching of IgM to IgG
|l3=Adaptive Immunity to Bacteria
|q4=What is the response to a vesicular bacterial infection?
|a4=
*IL-12 released from an infected macrophage
*T helper type I cells stimulated
*IFN-γ released triggering the macrophages to destroy the bacteria
|l4=Adaptive Immunity to Bacteria
</FlashCard>
===Adaptive Immunity to Parasites===
<FlashCard questions="1">
|q1=What is the humoral response to a parasitic infection?
|a1=Production of IgE
|l1=Adaptive Immunity to Parasites
</FlashCard>

 
{{Jim Bee 2007}}
[[Category:Immunology Flashcards]]
[[Category:Adaptive Immune System|Z]]

Adaptive Immunity Flashcards

2012-05-28T11:39:55Z

Rjfrancisrvc: /* Actions and Tools of the Adaptive Immune System */

===Actions and Tools of the Adaptive Immune System===
<FlashCard questions="6">
|q1=Complete the sentence:
T cell receptors recognise ??? fragments on the cell surface. B cell receptors recognise ??? in the ??? fluid.
|a1=
*antigen
*whole antigen
*extracellular
|l1=Adaptive Immune System - Overview#Antigen Recognition
|q2=Dendritic cells and macrophages are types of which kind of cells?
|a2=Antigen presenting cells (APCs)
|l2=Adaptive Immune System - Overview#Antigen Recognition
|q3=What can CD3+ T cells differentiate into?
|a3=
*CD4+ Helper T cells
*CD8+ Cytotoxic T cells
|l3=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q4=What is the main function of T helper I (TH1) cells?
|a4=Enhancing the macrophage response
|l4=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q5=What is the main function of T helper II (TH2) cells?
|a5=Enhancing the B cell antibody production
|l5=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q6=Name 3 types of antigen binding molecules
|a6=
*Immunolglobulins
*T cell receptors (TCRs)
*Natural Killer cells (NK cells)
|l6=Adaptive Immune System - Overview#Antigen Binding Molecules
</FlashCard>

===Adaptive Immunity to Viruses===
<FlashCard questions="3">
|q1=Which humoral factors are used against viruses in the adaptive response?
|a1=
*Production of neutralising antibody
*Antibody-dependent cell mediated cytotoxicity (ADCC)
|l1=Adaptive Immunity to Viruses
|q2=What is the cell mediated adaptive response against viruses?
|a2=CD8+ T-cell mediated killing of virus infected cells
|l2=Adaptive Immunity to Viruses
|q3=How are viral infected cells killed by apoptosis?
|a3=
*Perforin and granzymes released to activate the caspase cascade
*Fas-ligand triggers the Fas-mediated apoptosis pathway
*Cytotoxic cytokines act on TNF receptors to induce programmed cell death
|l3=Adaptive Immunity to Viruses
</FlashCard>
===Adaptive Immunity to Bacteria===
<FlashCard questions="4">
|q1=What is the humoral response to bacterial infection?
|a1=
*Complement activation of the classical pathway
*Production of IgM and IgG
|l1=Adaptive Immunity to Bacteria
|q2=What is the cell-mediated response to bacterial infection?
|a2=
*Help for macrophages
*Production of IgG
*T helper type I cell help
|l2=Adaptive Immunity to Bacteria
|q3=What is the response to an extracellular bacterial infection?
|a3=Complement and phagocytosis
*Production of IgM
*T helper type II and B cell production
*Class switching of IgM to IgG
|l3=Adaptive Immunity to Bacteria
|q4=What is the response to a vesicular bacterial infection?
|a4=
*IL-12 released from an infected macrophage
*T helper type I cells stimulated
*IFN-γ released triggering the macrophages to destroy the bacteria
|l4=Adaptive Immunity to Bacteria
</FlashCard>
===Adaptive Immunity to Parasites===
<FlashCard questions="1">
|q1=What is the humoral response to a parasitic infection?
|a1=Production of IgE
|l1=Adaptive Immunity to Parasites
</FlashCard>

 
{{Jim Bee 2007}}
[[Category:Immunology Flashcards]]
[[Category:Adaptive Immune System|Z]]

Adaptive Immunity Flashcards

2012-05-28T11:38:55Z

Rjfrancisrvc: /* Actions and Tools of the Adaptive Immune System */

===Actions and Tools of the Adaptive Immune System===
<FlashCard questions="6">
|q1=Complete the sentence:
T cell receptors recognise ??? fragments on the cell surface. B cell receptors recognise ??? in the ??? fluid.
|a1=
*antigen
*whole antigen
*extracellular
|l1=Adaptive Immune System - Overview#Antigen Recognition
|q2=Dendritic cells and macrophages are types of which kind of cells?
|a2=Antigen presenting cells (APCs)
|l2=Adaptive Immune System - Overview#Antigen Recognition
|q3=What can CD3+ T cells differentiate into?
|a3=
*CD4+ Helper T cells
*CD8+ Cytotoxic T cells
|l3=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q4=What is the main function of T helper I cells?
|a4=Enhancing the macrophage response
|l4=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q5=What is the main function of T helper II cells?
|a5=Enhancing the B cell antibody production
|l5=Adaptive Immune System - Overview#Cellular response: Proliferation and Differentiation
|q6=Name 3 types of antigen binding molecules
|a6=
*Immunolglobulins
*T cell receptors (TCRs)
*Natural Killer cells (NK cells)
|l6=Adaptive Immune System - Overview#Antigen Binding Molecules
</FlashCard>

===Adaptive Immunity to Viruses===
<FlashCard questions="3">
|q1=Which humoral factors are used against viruses in the adaptive response?
|a1=
*Production of neutralising antibody
*Antibody-dependent cell mediated cytotoxicity (ADCC)
|l1=Adaptive Immunity to Viruses
|q2=What is the cell mediated adaptive response against viruses?
|a2=CD8+ T-cell mediated killing of virus infected cells
|l2=Adaptive Immunity to Viruses
|q3=How are viral infected cells killed by apoptosis?
|a3=
*Perforin and granzymes released to activate the caspase cascade
*Fas-ligand triggers the Fas-mediated apoptosis pathway
*Cytotoxic cytokines act on TNF receptors to induce programmed cell death
|l3=Adaptive Immunity to Viruses
</FlashCard>
===Adaptive Immunity to Bacteria===
<FlashCard questions="4">
|q1=What is the humoral response to bacterial infection?
|a1=
*Complement activation of the classical pathway
*Production of IgM and IgG
|l1=Adaptive Immunity to Bacteria
|q2=What is the cell-mediated response to bacterial infection?
|a2=
*Help for macrophages
*Production of IgG
*T helper type I cell help
|l2=Adaptive Immunity to Bacteria
|q3=What is the response to an extracellular bacterial infection?
|a3=Complement and phagocytosis
*Production of IgM
*T helper type II and B cell production
*Class switching of IgM to IgG
|l3=Adaptive Immunity to Bacteria
|q4=What is the response to a vesicular bacterial infection?
|a4=
*IL-12 released from an infected macrophage
*T helper type I cells stimulated
*IFN-γ released triggering the macrophages to destroy the bacteria
|l4=Adaptive Immunity to Bacteria
</FlashCard>
===Adaptive Immunity to Parasites===
<FlashCard questions="1">
|q1=What is the humoral response to a parasitic infection?
|a1=Production of IgE
|l1=Adaptive Immunity to Parasites
</FlashCard>

 
{{Jim Bee 2007}}
[[Category:Immunology Flashcards]]
[[Category:Adaptive Immune System|Z]]

Immunoglobulins - Overview

2012-05-28T11:26:32Z

Rjfrancisrvc: /* Degranulation of mast cells/eosinophils */

{{review}}
[[Image:LH Antibody.png|thumb|200px|right|'''Immunoglobulin''' Je_at_uwo 2006, WikiMedia Commons]]
Also known as '''''antibodies
==Introduction==
''Also called antibodies''
Immunoglobulins (Ig) are the soluble form of B cell receptors (BCR) released by plasma cells after they have been activated. Immunoglobulins have to bind to a number of different antigens in a variety of environments and as such there are several different immunoglobulin classes. Each class has an optimum environment of action.
==Structure==
[[Image:LH Ig.png|thumb|200px|right|'''Immunoglobulin''' Asher Allison 2008]]

Antibodies are "Y-shaped" and consist of two identical heavy (H) chains and two identical light (L) chains with each H chain being linked to an L chain. The heavy chain consists of 4 or 5 protein domains, 1 amino terminal variable domain and 3 or 4 constant domains. Each light chain has one variable and one constant domain. Each arm of the molecule consists of one L chain and part of an H chain and there are two identical antigen-binding sites on each antibody molecule, one at the tip of each arm. The binding sites are made up of a combination of the variable domains of 1H and 1L, although single cells only have receptors of one specificity. The antigen binding site of an antibody is determined by a combination of the amino acid sequence of both the heavy and light chain variable domains (VH and VL). Antibodies of different specificities have different amino acids within one of three regions of the variable domains and these are called the hypervariable regions. The '''variable domains''' are '''folded''' in such a way as to form a pocket into which antigens fit. The '''constant domains''' do '''not''' bind antigen, although they determine the biological functions of the antibody molecules.
 
 
At the carboxyl terminus of B-cell expressed Ig is a region that holds the antibody molecule in the cell membrane. Secreted 'free' antibodies do not possess this region. The '''Fab''' fragments of the immunoglobulin is the '''antigen binding fragment''' generated from the light chains when digested by papain (proteolytic enzyme). The '''Fc''' fragment is the fragment produced by '''papain from the heavy chains''' and this fragment '''mediates [[Phagocytosis|phagocytosis]]''', triggers '''[[Inflammation|inflammation]]''', activates '''[[Complement|complement]]''' and '''targets Ig''' to certain tissues.

==Function==
[[Image:Ab-antigen.jpg|thumb|right|150px|Antibody binds 2 whole antigen molecules - B. Catchpole, RVC 2008]]
Antibodies form part of the adaptive immune response. For further information on the adaptive immune response, see [[:Category:Adaptive Immune System|here]]. All antibody classes bind antigen in a similar manner; the initial trigger for all antibody function is the association of antigen with the antigen-binding sites of the immunoglobulin molecules. However, different classes serve different physiological functions and functional differences between antibody classes are reflected in the structural differences in their '''heavy chain constant regions'''. These heavy chain regions comprise the '''effector domains''' of antibody molecules. In general antibodies have four major effector functions:
 
 
==='''Blockade and agglutination'''===
This action of antibody binding to antigen is a protective function. Antibody may bind to biologically active sites on toxins, inhibiting their binding sites. In a similar manner, antibody can bind the surface of viruses and prevent them from infecting cells. Antibody molecules are at least divalent, and many are greater than divalent which means that antibody can cross-link antibody forming an antibody '''agglutination'''. The ability to cross-link or agglutinate can be the primary function of the antibody. In order to be pathogenic, many micro-organisms must be able to contact viable host cells. If antibody molecules agglutinate these micro-organisms, any cell contact is prevented and the pathogenic effect is removed or reduced. The main biological function of '''[[Immunoglobulin A|IgA]]''' is to cross-link potentially pathogenic molecules.
 
 
==='''Promotion of phagocytosis'''===
Antibodies also have a function to facilitate [[Phagocytosis|phagocytosis]]. Phagocytes have receptors for the '''Fc''' portion of antibody, using '''Fc receptors (FcR)'''. FcR bind the Fc portion of antibody on antigen/antibody (Ag/Ab) complexes, although the antibody alone does not interact with FcR. Interaction of FcR with Ag/Ab complexes stimulates '''cellular activation''' which greatly increases the efficiency of phagocytosis. This process is called '''opsonisation'''. Opsonisation promotes the '''production of intracellular enzymes''' and therefore promotes the killing and digestion of internalised micro-organisms. Systems used by phagocytes that are important in intracellular killing include free radicals such as oxygen and chlorine, hydrogen peroxidase and nitric oxide produced by nitric oxide synthase. Ultimately phagocytes undergo '''degranulation''' resulting in the '''secretion of certain enzymes and cytotoxic molecules'''. These systems are also activated by the interferons, especially the immune interferon, interferon gamma (IFNγ). Antibody-mediated opsonisation of micro organisms is much more efficient that innate immune system receptors. Phagocytes also have receptors for iC3b, a [[Complement|complement]] component which is also a major initiator of opsonisation. Two particulary important phagocytic cells that have FcR are the [[Neutrophils|neutrophils]] and [[Macrophages|macrophages]].
 
 

==='''Degranulation of [[Mast Cells|mast cells]]/[[Eosinophils|eosinophils]]'''===
Antibodies play an important role in the [[Innate Immunity Cellular Responses|innate immune response]] to parasites. The Eosinophils and Mast Cells have FcR that are specific to IgE. When the IgE are cross-linked by antigen the eosinophils and Mast cells can interact with the IgE causing the release of their granules through the process known as exocytosis (granule fusion with the plasma membrane). This causes proteolytic enzyme release from eosinophils, and vasoactive peptide and cytokine release by Mast cells which then activates the innate immune response. Interestingly, this response is also responsible for the Type I hypersensitivity reaction.

==='''[[Complement|Complement fixation]]'''===
Cross-linking two Fc regions of IgM and IgG by complement component C1q begins the [[Complement| classical complement pathway]]. As IgM has '''five''' Fc regions it is a much better activator of complement than IgG (as IgG only has '''one''' Fc region).

==Classes==
There are five classes of Immunoglobulins, which vary due to the composition of their heavy chains. These are common across mammals but subclasses of them do vary between species. '''IgY''' is present in yolk.
{|style="border:3px solid;" cellpadding="0"
|width="150"|
!width="200"|[[IgA]]
!width="200"|[[IgD]]
!width="200"|[[IgE]]
!width="200"|[[IgG]]
!width="200"|[[IgM]]
|-align="middle"
!Weight (kDa)
|360
|180
|200
|180
|900
|-align="middle"
!No. subunits
|2
|1
|1
|1
|5
|-align="middle"
!Heavy chain
|α
|δ
|ε
|γ
|µ
|-align="middle"
!Mainsite of production
|Alimentary/Respiratory tracts
|Spleen/Lymph nodes
|Alimentary/Respiratory tracts
|Spleen/Lymph nodes
|Spleen/Lymph nodes
|}

==Variation==
===Subclasses===
Subclasses of the five major classes also exist. These occur in the '''heavy chains''' and are coded for by the IGH gene. For examples horses have six subclasses of the [[IgG]] immunoglobulin coded for by the genes IGHG1→ IGHG6 while cattle and sheep only have three subclasses (IGHG1→ IGHG3). Therefore within the [[IgG]] class there are '''several subclasses depending on the species'''. Humans and rodents have four [[IgG]] subclasses, dogs have three subclasses, ruminants have two or three subclasses and in some species there are also two IgA subclasses. Antibody specificity is unrelated to class. Different classes of antibody can be associated with the same V domains and have the same specificity. It is possible for a single B-cell to produce antibody of one specificity but two or more classes. A mature B-cell has the genetic capacity to produce antibody of all classes and subclasses but of one specificity only.
 
 
===Allo & Idiotypes===
Allotypes are differences in immunoglobulins between individuals of a particular species. They are inheritable. Idiotypes are variations in the sequences of amino acids in the variable regions of the light and heavy chains.
 
 
===Immunoglobulin Class Switching===
Different classes of antibody differ from each other in size, charge, amino acid composition, associated carbohydrate and function. Immunoglobulin heavy and light chains are encoded by separate genes with the first 300 bases of each gene encoding the variable part of each protein chain. The combination of the VH and VL contribute to the antigenic specificity and any individual has the capability of producing over 100 million different antibody specificities. The rest of the antibody gene encodes all the constant domains. There are five different types of heavy chain constant domains - μ, γ, ε, α. Different heavy chains are associated with different classes of antibody;
 
* '''μ chain - [[IgM]] '''
* '''γ chain -[[IgG]]'''
* '''ε chain - [[IgE]]'''
* '''α chain - [[IgA]]'''
 
In humans and mice there exists a fifth Ig class, '''[[IgD]] (δ chain)'''. IgD is always expressed on B-cell membranes with [[IgM]] but is ''never secreted''. The sequence of constant region genes on the chromosome is M, G, E and A. In humans/ rodents the Cδ ([[IgD]]) is immediately downstream of the M gene and prior to antigenic stimulation, B-cells express cell membrane-associated [[IgM]].
 
 
The first immunoglobulin produced during an immune response is '''always [[IgM]]''' because the Cμ gene is the first constant H chain gene downstream of the variable domain. After antigenic exposure the [[IgM]]+ B-cells differentiate and begin to synthesise other classes of immunoglobulin, but only under the '''direct influence of a T-cell'''. This system is known as '''immunoglobulin heavy chain switching'''. The [[IgG]] antibodies produced in both primary and secondary responses originate from the same clones of B-cells as the [[IgM]] antibodies. The different antibody classes have the same variable domain combinations, and therefore the same antigenic specificity. Under the influence of T-cells, B-cells undergo immunoglobulin heavy chain switching and the B-cells mature from [[IgM]] to [[IgG]] producers, with [[IgE]] and [[IgA]] producers generated under certain immune responses. These immunoglobulins (IgA and IgE) tend to be produced within lymphoid tissue associated with mucosal surfaces.
 
 

==Clinical Uses==
[[Vaccines|Vaccination]]

[[Immunological Testing]]

{{Template:Learning
|flashcards = [[Immunoglobulins Flashcards]]
}}

==Links==
'''Websites'''
*http://www.cellsalive.com
 
{{Jim Bee 2007}}
[[Category:Immunoglobulins|A]]
[[Category:A&P Done]]

Leukopoiesis

2012-05-28T11:23:42Z

Rjfrancisrvc: /* Lymphopoiesis */

[[Image:Leukopoiesis pathway.jpg|right|thumb|400px|'''Leukopoiesis pathway''']]
==Introduction==
Leukopoiesis is the process of formation of [[Leukocytes|leukocytes]] (white blood cells) from stem cells in haematopoietic organs. Leukocytes develop from either multipotential myeloid stem cells ([[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]]) or multipotential lymphoid stem cells ([[Haematopoiesis - Overview#Colony Forming Units|CFU-L]]). 
Leukocytes developing from CFU-GEMM’s are granulocytes ([[Neutrophils|neutrophils]], [[Basophils| basophils]] and [[Eosinophils| eosinophils]]) or [[Monocytes|monocytes]].
Leukocytes developing from CFU-Ls are [[:Category:Lymphocytes|lymphocytes]] (T & B cells, dendritic and NK cells).

==Granulopoiesis==
All granulocytes develop from the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]] cells.
===Summary of pathways===
<div style="text-align: center;">
{| cellpadding="10" cellspacing="0" border="1" align="left"
|
!Monocyte
!Neutrophil
!Basophil
!Eosinophil
|rowspan="10"|[[Image:LH_Developing_granulocytes_Histology.jpg|200px|Developing granulocytes]]©RVC 2008
|-
!Stem cell
|colspan="4"|CFU-GEMM
|-
!CFU
|CFU-M
|CFU-G
|CFU-Ba
|CFU-Eo
|-
!Cytokines
|GM-CSFIL-3M-CSF
|GM-CSFIL-3G-CSF
|valign="top"|GM-CSFIL-3
|GM-CSFIL-3IL-5
|-
!Rowspan="6"|Stages
|Monoblast
|colspan="3"|Myelocyte
|-
|Promonocyte
|colspan="3"|Promyelocyte
|-
|rowspan="4"|Monocyte
|Neutrophilic Myelocyte
|Basophilic Myelocyte
|Eosinophilic Myelocyte
|-
|Neutrophilic Metamyelocyte
|rowspan="2"|Basophilic Metamyelocyte
|rowspan="2"|Eosinophilic Metamyelocyte
|-
|Band Cell
|-
|Neutrophil
|Basophil
|Eosinophil
|}
</div>
 

==Neutrophils==
Under the stimulation of [[Cytokines|cytokines]] GM-CSF, G-CSF and IL-3 the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]] differentiates into the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GM]], the common precursor for both neutrophils and monocytes. This then further differentiates into [[Haematopoiesis - Overview#Colony Forming Units|CFU-G]].
===Stages:===
====Myeloblast====
Large cell with a large nucleus and which demonstrates basophilic staining. This stage exists for all granulocytes.

====Promyelocyte====
During this stage primary (azurophilic) granules are formed. This stage exists for all granulocytes.

====Neutrophilic myelocyte====
The developing neutrophil can now be differentiated from basophils and eosinophils as neutrophil specific granules are now being formed.

====Neutrophilic metamyelocyte====
At this stage mitosis can no longer occur. The nucleus elongates, becomes heterochromatic and has a kidney like shape. Differentiation is now much clearer from other granulocytes as the specific granules are in a far greater number than the primary granules formed in the promyelocyte stage.

====Band cell====
Nucleus elongates further and represents a horse shoe. Nucleus starts to segment.
====Neutrophil====
Mature neutrophil is formed and the nucleus is segmented and has 3 to 5 lobes. This lobular structure of the nucleus gives rise to the name polymorphonuclear neutrophil.
 

==Basophils==
Under the stimulation of GM-CSF and IL-3, the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]] differentiates into [[Haematopoiesis - Overview#Colony Forming Units|CFU-Ba]].
===Stages:===
====Myeloblast & Promyelocyte====
These stages are common to all granulocytes and no distinction can be made between different cell lines.

====Basophilic myelocyte & metamyelocyte====
Specific granules start to appear in the myelocyte stage, and as the cell develops into the metamyelocyte stage, mitosis ceases.

====Basophil====
Final nuclear shape is masked by the high density of cytoplasmic granules.
 

==Eosinophils==
Under the stimulation of GM-CSF, IL-3 and IL-5 the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]] differentiates into the [[Haematopoiesis - Overview#Colony Forming Units|CFU-Eo]].
===Stages:===
====Myeloblast & Promyelocyte====
These stages are common to all granulocytes and no distinction can be made between different cell lines.

====Eosinophilic myelocyte & metamyelocyte====
Specific granules start to appear in the myelocyte stage and once the cell has reached the metamyelocyte stage it cannot undergo further mitosis.
====Eosinophil====
Mature cell has a bilobed nucleus. There are species specific variations in granule size once stained.
 

==Monocytes==
Monocytes develop from the same precursor as neutrophils - the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GM]]. This then differentiates into the [[Haematopoiesis - Overview#Colony Forming Units|CFU-M]] under the influence of GM-CSF, IL-3 and M-CSF.
===Stages:===
====Monoblast====
This is the first stage after cell has differentiated into the [[Haematopoiesis - Overview#Colony Forming Units|CFU-M]].
====Promonocyte====
Cell has a large nucleus and basophilic cytoplasm and consists of two populations:- One rapidly dividing and the other slowly dividing, which acts as a reservoir.
====Monocyte====
Monocytes are incapable of mitosis and enter the circulation. They have a large kidney shaped nucleus with a slightly basophilic cytoplasm, which is often vacuolated.

====Macrophage====
Once the monocyte has entered tissue it differentiates into a macrophage.

===Dendritic cells===
These develop from the monoblast under the stimualtion of GM-CSF and IL-4 into an immature dendritic cell. This then develops into the mature [[T_cell_differentiation#Dendritic_Cells|dendritic cell]] under stimulation of TNF-α.
 

==Lymphopoiesis==
[[Lymphocytes - Introduction|Lymphocytes]] develop from the [[Haematopoiesis - Overview#Colony Forming Units|CFU-L]]'s. Those destined to become [[T cells]] leave the [[Bone Marrow - Anatomy & Physiology|bone marrow]] and migrate to the [[Thymus - Anatomy & Physiology|thymus]], and those destined to be [[B cells]] migrate to the [[Spleen - Anatomy & Physiology|spleen]] and gut-associated lymphoid tissue (GALT) or proliferate directly from the bone marrow.
{|cellpadding="5" cellspacing="1" border="1"
|
!style="background-color:#ffffcc"|B cell
!colspan="3" style="background-color:#e6e6fa"|T cell
|-align="center"
!rowspan="5"|Differentiation
|colspan="4"|CFU-L
|-align="center"
|style="background-color:#ffffcc"|▼IL-7 & IL-11
|colspan="3" style="background-color:#e6e6fa"|▼IL-7 & SCF
|-align="center"
|style="background-color:#ffffcc"|B lymphoid cell progenitor
|colspan="3" style="background-color:#e6e6fa"|T lymphoid cell progenitor
|-align="center"
|style="background-color:#ffffcc"|▼IL-3 & IL-7
|style="background-color:#e6e6fa"|▼IL-7
|style="background-color:#e6e6fa"|▼IL-2, IL-12 & IL-18
|style="background-color:#e6e6fa"|▼IL-3, IL-6, GM-CSF & SCF
|-align="center"
|style="background-color:#ffffcc"|Pre-B cell
|style="background-color:#e6e6fa"|Pre-T cell
|style="background-color:#e6e6fa"|Pre-NK cell
|style="background-color:#e6e6fa"|Pre-Dendritic cell
|-align="center"
!Maturationsite
|style="background-color:#ffffcc"|Bone marrow, spleen or GALTCloacal bursa (birds)
|style="background-color:#e6e6fa" colspan="3"|Thymus
|-align="center"
!Mature
|style="background-color:#ffffcc"|'''B cell'''▼(Antigen stim.)'''Plasma & Memory cell'''
|style="background-color:#e6e6fa"|'''T Cell'''HelperCytotoxicRegulatory
|style="background-color:#e6e6fa"|'''NK cell'''
|style="background-color:#e6e6fa"|'''Dendritic cell'''
|}
'''Note:'''
*Between the 'pre-[type] cell' stage and the final mature all the lymphocytes are referred to as 'immature [type] cells'.
* T cell differentiation into helper, cytotoxic and T cells with regulator functions is induced by IL-10 & TNF-γ
[[Category:Haematopoiesis]]

Leukopoiesis

2012-05-28T11:22:35Z

Rjfrancisrvc: /* Eosinophils */

[[Image:Leukopoiesis pathway.jpg|right|thumb|400px|'''Leukopoiesis pathway''']]
==Introduction==
Leukopoiesis is the process of formation of [[Leukocytes|leukocytes]] (white blood cells) from stem cells in haematopoietic organs. Leukocytes develop from either multipotential myeloid stem cells ([[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]]) or multipotential lymphoid stem cells ([[Haematopoiesis - Overview#Colony Forming Units|CFU-L]]). 
Leukocytes developing from CFU-GEMM’s are granulocytes ([[Neutrophils|neutrophils]], [[Basophils| basophils]] and [[Eosinophils| eosinophils]]) or [[Monocytes|monocytes]].
Leukocytes developing from CFU-Ls are [[:Category:Lymphocytes|lymphocytes]] (T & B cells, dendritic and NK cells).

==Granulopoiesis==
All granulocytes develop from the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]] cells.
===Summary of pathways===
<div style="text-align: center;">
{| cellpadding="10" cellspacing="0" border="1" align="left"
|
!Monocyte
!Neutrophil
!Basophil
!Eosinophil
|rowspan="10"|[[Image:LH_Developing_granulocytes_Histology.jpg|200px|Developing granulocytes]]©RVC 2008
|-
!Stem cell
|colspan="4"|CFU-GEMM
|-
!CFU
|CFU-M
|CFU-G
|CFU-Ba
|CFU-Eo
|-
!Cytokines
|GM-CSFIL-3M-CSF
|GM-CSFIL-3G-CSF
|valign="top"|GM-CSFIL-3
|GM-CSFIL-3IL-5
|-
!Rowspan="6"|Stages
|Monoblast
|colspan="3"|Myelocyte
|-
|Promonocyte
|colspan="3"|Promyelocyte
|-
|rowspan="4"|Monocyte
|Neutrophilic Myelocyte
|Basophilic Myelocyte
|Eosinophilic Myelocyte
|-
|Neutrophilic Metamyelocyte
|rowspan="2"|Basophilic Metamyelocyte
|rowspan="2"|Eosinophilic Metamyelocyte
|-
|Band Cell
|-
|Neutrophil
|Basophil
|Eosinophil
|}
</div>
 

==Neutrophils==
Under the stimulation of [[Cytokines|cytokines]] GM-CSF, G-CSF and IL-3 the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]] differentiates into the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GM]], the common precursor for both neutrophils and monocytes. This then further differentiates into [[Haematopoiesis - Overview#Colony Forming Units|CFU-G]].
===Stages:===
====Myeloblast====
Large cell with a large nucleus and which demonstrates basophilic staining. This stage exists for all granulocytes.

====Promyelocyte====
During this stage primary (azurophilic) granules are formed. This stage exists for all granulocytes.

====Neutrophilic myelocyte====
The developing neutrophil can now be differentiated from basophils and eosinophils as neutrophil specific granules are now being formed.

====Neutrophilic metamyelocyte====
At this stage mitosis can no longer occur. The nucleus elongates, becomes heterochromatic and has a kidney like shape. Differentiation is now much clearer from other granulocytes as the specific granules are in a far greater number than the primary granules formed in the promyelocyte stage.

====Band cell====
Nucleus elongates further and represents a horse shoe. Nucleus starts to segment.
====Neutrophil====
Mature neutrophil is formed and the nucleus is segmented and has 3 to 5 lobes. This lobular structure of the nucleus gives rise to the name polymorphonuclear neutrophil.
 

==Basophils==
Under the stimulation of GM-CSF and IL-3, the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]] differentiates into [[Haematopoiesis - Overview#Colony Forming Units|CFU-Ba]].
===Stages:===
====Myeloblast & Promyelocyte====
These stages are common to all granulocytes and no distinction can be made between different cell lines.

====Basophilic myelocyte & metamyelocyte====
Specific granules start to appear in the myelocyte stage, and as the cell develops into the metamyelocyte stage, mitosis ceases.

====Basophil====
Final nuclear shape is masked by the high density of cytoplasmic granules.
 

==Eosinophils==
Under the stimulation of GM-CSF, IL-3 and IL-5 the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]] differentiates into the [[Haematopoiesis - Overview#Colony Forming Units|CFU-Eo]].
===Stages:===
====Myeloblast & Promyelocyte====
These stages are common to all granulocytes and no distinction can be made between different cell lines.

====Eosinophilic myelocyte & metamyelocyte====
Specific granules start to appear in the myelocyte stage and once the cell has reached the metamyelocyte stage it cannot undergo further mitosis.
====Eosinophil====
Mature cell has a bilobed nucleus. There are species specific variations in granule size once stained.
 

==Monocytes==
Monocytes develop from the same precursor as neutrophils - the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GM]]. This then differentiates into the [[Haematopoiesis - Overview#Colony Forming Units|CFU-M]] under the influence of GM-CSF, IL-3 and M-CSF.
===Stages:===
====Monoblast====
This is the first stage after cell has differentiated into the [[Haematopoiesis - Overview#Colony Forming Units|CFU-M]].
====Promonocyte====
Cell has a large nucleus and basophilic cytoplasm and consists of two populations:- One rapidly dividing and the other slowly dividing, which acts as a reservoir.
====Monocyte====
Monocytes are incapable of mitosis and enter the circulation. They have a large kidney shaped nucleus with a slightly basophilic cytoplasm, which is often vacuolated.

====Macrophage====
Once the monocyte has entered tissue it differentiates into a macrophage.

===Dendritic cells===
These develop from the monoblast under the stimualtion of GM-CSF and IL-4 into an immature dendritic cell. This then develops into the mature [[T_cell_differentiation#Dendritic_Cells|dendritic cell]] under stimulation of TNF-α.
 

==Lymphopoiesis==
[[Lymphocytes - Introduction|Lymphocytes]] develop from the [[Haematopoiesis - Overview#Colony Forming Units|CFU-L]]'s. Those destined to become [[T cells]] leave the [[Bone Marrow - Anatomy & Physiology|bone marrow]] and migrate to the [[Thymus - Anatomy & Physiology|thymus]], and those destined to be [[B cells]] migrate to the [[Spleen - Anatomy & Physiology|spleen]] and gut-associated lymphoid tissue (GALT) or proliferate directly from the bone marrow.
{|cellpadding="5" cellspacing="1" border="1"
|
!style="background-color:#ffffcc"|B cell
!colspan="3" style="background-color:#e6e6fa"|T cell
|-align="center"
!rowspan="5"|Differentiation
|colspan="4"|CFU-L
|-align="center"
|style="background-color:#ffffcc"|▼Il-7 & Il-11
|colspan="3" style="background-color:#e6e6fa"|▼Il-7 & SCF
|-align="center"
|style="background-color:#ffffcc"|B lymphoid cell progenitor
|colspan="3" style="background-color:#e6e6fa"|T lymphoid cell progenitor
|-align="center"
|style="background-color:#ffffcc"|▼Il-3 & Il-7
|style="background-color:#e6e6fa"|▼Il-7
|style="background-color:#e6e6fa"|▼Il-2, IL-12 & Il-18
|style="background-color:#e6e6fa"|▼Il-3, Il-6, GM-CSF & SCF
|-align="center"
|style="background-color:#ffffcc"|Pre-B cell
|style="background-color:#e6e6fa"|Pre-T cell
|style="background-color:#e6e6fa"|Pre-NK cell
|style="background-color:#e6e6fa"|Pre-Dendritic cell
|-align="center"
!Maturationsite
|style="background-color:#ffffcc"|Bone marrow, spleen or GALTCloacal bursa (birds)
|style="background-color:#e6e6fa" colspan="3"|Thymus
|-align="center"
!Mature
|style="background-color:#ffffcc"|'''B cell'''▼(Antigen stim.)'''Plasma & Memory cell'''
|style="background-color:#e6e6fa"|'''T Cell'''HelperCytotoxicRegulatory
|style="background-color:#e6e6fa"|'''NK cell'''
|style="background-color:#e6e6fa"|'''Dendritic cell'''
|}
'''Note:'''
*Between the 'pre-[type] cell' stage and the final mature all the lymphocytes are referred to as 'immature [type] cells'.
* T cell differentiation into helper, cytotoxic and T cells with regulator functions is induced by Il-10 & TNF-γ
[[Category:Haematopoiesis]]

Leukopoiesis

2012-05-28T11:22:22Z

Rjfrancisrvc: /* Basophils */

[[Image:Leukopoiesis pathway.jpg|right|thumb|400px|'''Leukopoiesis pathway''']]
==Introduction==
Leukopoiesis is the process of formation of [[Leukocytes|leukocytes]] (white blood cells) from stem cells in haematopoietic organs. Leukocytes develop from either multipotential myeloid stem cells ([[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]]) or multipotential lymphoid stem cells ([[Haematopoiesis - Overview#Colony Forming Units|CFU-L]]). 
Leukocytes developing from CFU-GEMM’s are granulocytes ([[Neutrophils|neutrophils]], [[Basophils| basophils]] and [[Eosinophils| eosinophils]]) or [[Monocytes|monocytes]].
Leukocytes developing from CFU-Ls are [[:Category:Lymphocytes|lymphocytes]] (T & B cells, dendritic and NK cells).

==Granulopoiesis==
All granulocytes develop from the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]] cells.
===Summary of pathways===
<div style="text-align: center;">
{| cellpadding="10" cellspacing="0" border="1" align="left"
|
!Monocyte
!Neutrophil
!Basophil
!Eosinophil
|rowspan="10"|[[Image:LH_Developing_granulocytes_Histology.jpg|200px|Developing granulocytes]]©RVC 2008
|-
!Stem cell
|colspan="4"|CFU-GEMM
|-
!CFU
|CFU-M
|CFU-G
|CFU-Ba
|CFU-Eo
|-
!Cytokines
|GM-CSFIL-3M-CSF
|GM-CSFIL-3G-CSF
|valign="top"|GM-CSFIL-3
|GM-CSFIL-3IL-5
|-
!Rowspan="6"|Stages
|Monoblast
|colspan="3"|Myelocyte
|-
|Promonocyte
|colspan="3"|Promyelocyte
|-
|rowspan="4"|Monocyte
|Neutrophilic Myelocyte
|Basophilic Myelocyte
|Eosinophilic Myelocyte
|-
|Neutrophilic Metamyelocyte
|rowspan="2"|Basophilic Metamyelocyte
|rowspan="2"|Eosinophilic Metamyelocyte
|-
|Band Cell
|-
|Neutrophil
|Basophil
|Eosinophil
|}
</div>
 

==Neutrophils==
Under the stimulation of [[Cytokines|cytokines]] GM-CSF, G-CSF and IL-3 the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]] differentiates into the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GM]], the common precursor for both neutrophils and monocytes. This then further differentiates into [[Haematopoiesis - Overview#Colony Forming Units|CFU-G]].
===Stages:===
====Myeloblast====
Large cell with a large nucleus and which demonstrates basophilic staining. This stage exists for all granulocytes.

====Promyelocyte====
During this stage primary (azurophilic) granules are formed. This stage exists for all granulocytes.

====Neutrophilic myelocyte====
The developing neutrophil can now be differentiated from basophils and eosinophils as neutrophil specific granules are now being formed.

====Neutrophilic metamyelocyte====
At this stage mitosis can no longer occur. The nucleus elongates, becomes heterochromatic and has a kidney like shape. Differentiation is now much clearer from other granulocytes as the specific granules are in a far greater number than the primary granules formed in the promyelocyte stage.

====Band cell====
Nucleus elongates further and represents a horse shoe. Nucleus starts to segment.
====Neutrophil====
Mature neutrophil is formed and the nucleus is segmented and has 3 to 5 lobes. This lobular structure of the nucleus gives rise to the name polymorphonuclear neutrophil.
 

==Basophils==
Under the stimulation of GM-CSF and IL-3, the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]] differentiates into [[Haematopoiesis - Overview#Colony Forming Units|CFU-Ba]].
===Stages:===
====Myeloblast & Promyelocyte====
These stages are common to all granulocytes and no distinction can be made between different cell lines.

====Basophilic myelocyte & metamyelocyte====
Specific granules start to appear in the myelocyte stage, and as the cell develops into the metamyelocyte stage, mitosis ceases.

====Basophil====
Final nuclear shape is masked by the high density of cytoplasmic granules.
 

==Eosinophils==
Under the stimulation of GM-CSF, Il-3 and Il-5 the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]] differentiates into the [[Haematopoiesis - Overview#Colony Forming Units|CFU-Eo]].
===Stages:===
====Myeloblast & Promyelocyte====
These stages are common to all granulocytes and no distinction can be made between different cell lines.

====Eosinophilic myelocyte & metamyelocyte====
Specific granules start to appear in the myelocyte stage and once the cell has reached the metamyelocyte stage it cannot undergo further mitosis.
====Eosinophil====
Mature cell has a bilobed nucleus. There are species specific variations in granule size once stained.
 

==Monocytes==
Monocytes develop from the same precursor as neutrophils - the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GM]]. This then differentiates into the [[Haematopoiesis - Overview#Colony Forming Units|CFU-M]] under the influence of GM-CSF, IL-3 and M-CSF.
===Stages:===
====Monoblast====
This is the first stage after cell has differentiated into the [[Haematopoiesis - Overview#Colony Forming Units|CFU-M]].
====Promonocyte====
Cell has a large nucleus and basophilic cytoplasm and consists of two populations:- One rapidly dividing and the other slowly dividing, which acts as a reservoir.
====Monocyte====
Monocytes are incapable of mitosis and enter the circulation. They have a large kidney shaped nucleus with a slightly basophilic cytoplasm, which is often vacuolated.

====Macrophage====
Once the monocyte has entered tissue it differentiates into a macrophage.

===Dendritic cells===
These develop from the monoblast under the stimualtion of GM-CSF and IL-4 into an immature dendritic cell. This then develops into the mature [[T_cell_differentiation#Dendritic_Cells|dendritic cell]] under stimulation of TNF-α.
 

==Lymphopoiesis==
[[Lymphocytes - Introduction|Lymphocytes]] develop from the [[Haematopoiesis - Overview#Colony Forming Units|CFU-L]]'s. Those destined to become [[T cells]] leave the [[Bone Marrow - Anatomy & Physiology|bone marrow]] and migrate to the [[Thymus - Anatomy & Physiology|thymus]], and those destined to be [[B cells]] migrate to the [[Spleen - Anatomy & Physiology|spleen]] and gut-associated lymphoid tissue (GALT) or proliferate directly from the bone marrow.
{|cellpadding="5" cellspacing="1" border="1"
|
!style="background-color:#ffffcc"|B cell
!colspan="3" style="background-color:#e6e6fa"|T cell
|-align="center"
!rowspan="5"|Differentiation
|colspan="4"|CFU-L
|-align="center"
|style="background-color:#ffffcc"|▼Il-7 & Il-11
|colspan="3" style="background-color:#e6e6fa"|▼Il-7 & SCF
|-align="center"
|style="background-color:#ffffcc"|B lymphoid cell progenitor
|colspan="3" style="background-color:#e6e6fa"|T lymphoid cell progenitor
|-align="center"
|style="background-color:#ffffcc"|▼Il-3 & Il-7
|style="background-color:#e6e6fa"|▼Il-7
|style="background-color:#e6e6fa"|▼Il-2, IL-12 & Il-18
|style="background-color:#e6e6fa"|▼Il-3, Il-6, GM-CSF & SCF
|-align="center"
|style="background-color:#ffffcc"|Pre-B cell
|style="background-color:#e6e6fa"|Pre-T cell
|style="background-color:#e6e6fa"|Pre-NK cell
|style="background-color:#e6e6fa"|Pre-Dendritic cell
|-align="center"
!Maturationsite
|style="background-color:#ffffcc"|Bone marrow, spleen or GALTCloacal bursa (birds)
|style="background-color:#e6e6fa" colspan="3"|Thymus
|-align="center"
!Mature
|style="background-color:#ffffcc"|'''B cell'''▼(Antigen stim.)'''Plasma & Memory cell'''
|style="background-color:#e6e6fa"|'''T Cell'''HelperCytotoxicRegulatory
|style="background-color:#e6e6fa"|'''NK cell'''
|style="background-color:#e6e6fa"|'''Dendritic cell'''
|}
'''Note:'''
*Between the 'pre-[type] cell' stage and the final mature all the lymphocytes are referred to as 'immature [type] cells'.
* T cell differentiation into helper, cytotoxic and T cells with regulator functions is induced by Il-10 & TNF-γ
[[Category:Haematopoiesis]]

Leukopoiesis

2012-05-28T11:22:01Z

Rjfrancisrvc: /* Neutrophils */

[[Image:Leukopoiesis pathway.jpg|right|thumb|400px|'''Leukopoiesis pathway''']]
==Introduction==
Leukopoiesis is the process of formation of [[Leukocytes|leukocytes]] (white blood cells) from stem cells in haematopoietic organs. Leukocytes develop from either multipotential myeloid stem cells ([[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]]) or multipotential lymphoid stem cells ([[Haematopoiesis - Overview#Colony Forming Units|CFU-L]]). 
Leukocytes developing from CFU-GEMM’s are granulocytes ([[Neutrophils|neutrophils]], [[Basophils| basophils]] and [[Eosinophils| eosinophils]]) or [[Monocytes|monocytes]].
Leukocytes developing from CFU-Ls are [[:Category:Lymphocytes|lymphocytes]] (T & B cells, dendritic and NK cells).

==Granulopoiesis==
All granulocytes develop from the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]] cells.
===Summary of pathways===
<div style="text-align: center;">
{| cellpadding="10" cellspacing="0" border="1" align="left"
|
!Monocyte
!Neutrophil
!Basophil
!Eosinophil
|rowspan="10"|[[Image:LH_Developing_granulocytes_Histology.jpg|200px|Developing granulocytes]]©RVC 2008
|-
!Stem cell
|colspan="4"|CFU-GEMM
|-
!CFU
|CFU-M
|CFU-G
|CFU-Ba
|CFU-Eo
|-
!Cytokines
|GM-CSFIL-3M-CSF
|GM-CSFIL-3G-CSF
|valign="top"|GM-CSFIL-3
|GM-CSFIL-3IL-5
|-
!Rowspan="6"|Stages
|Monoblast
|colspan="3"|Myelocyte
|-
|Promonocyte
|colspan="3"|Promyelocyte
|-
|rowspan="4"|Monocyte
|Neutrophilic Myelocyte
|Basophilic Myelocyte
|Eosinophilic Myelocyte
|-
|Neutrophilic Metamyelocyte
|rowspan="2"|Basophilic Metamyelocyte
|rowspan="2"|Eosinophilic Metamyelocyte
|-
|Band Cell
|-
|Neutrophil
|Basophil
|Eosinophil
|}
</div>
 

==Neutrophils==
Under the stimulation of [[Cytokines|cytokines]] GM-CSF, G-CSF and IL-3 the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]] differentiates into the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GM]], the common precursor for both neutrophils and monocytes. This then further differentiates into [[Haematopoiesis - Overview#Colony Forming Units|CFU-G]].
===Stages:===
====Myeloblast====
Large cell with a large nucleus and which demonstrates basophilic staining. This stage exists for all granulocytes.

====Promyelocyte====
During this stage primary (azurophilic) granules are formed. This stage exists for all granulocytes.

====Neutrophilic myelocyte====
The developing neutrophil can now be differentiated from basophils and eosinophils as neutrophil specific granules are now being formed.

====Neutrophilic metamyelocyte====
At this stage mitosis can no longer occur. The nucleus elongates, becomes heterochromatic and has a kidney like shape. Differentiation is now much clearer from other granulocytes as the specific granules are in a far greater number than the primary granules formed in the promyelocyte stage.

====Band cell====
Nucleus elongates further and represents a horse shoe. Nucleus starts to segment.
====Neutrophil====
Mature neutrophil is formed and the nucleus is segmented and has 3 to 5 lobes. This lobular structure of the nucleus gives rise to the name polymorphonuclear neutrophil.
 

==Basophils==
Under the stimulation of GM-CSF and Il-3, the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]] differentiates into [[Haematopoiesis - Overview#Colony Forming Units|CFU-Ba]].
===Stages:===
====Myeloblast & Promyelocyte====
These stages are common to all granulocytes and no distinction can be made between different cell lines.

====Basophilic myelocyte & metamyelocyte====
Specific granules start to appear in the myelocyte stage, and as the cell develops into the metamyelocyte stage, mitosis ceases.

====Basophil====
Final nuclear shape is masked by the high density of cytoplasmic granules.
 

==Eosinophils==
Under the stimulation of GM-CSF, Il-3 and Il-5 the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]] differentiates into the [[Haematopoiesis - Overview#Colony Forming Units|CFU-Eo]].
===Stages:===
====Myeloblast & Promyelocyte====
These stages are common to all granulocytes and no distinction can be made between different cell lines.

====Eosinophilic myelocyte & metamyelocyte====
Specific granules start to appear in the myelocyte stage and once the cell has reached the metamyelocyte stage it cannot undergo further mitosis.
====Eosinophil====
Mature cell has a bilobed nucleus. There are species specific variations in granule size once stained.
 

==Monocytes==
Monocytes develop from the same precursor as neutrophils - the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GM]]. This then differentiates into the [[Haematopoiesis - Overview#Colony Forming Units|CFU-M]] under the influence of GM-CSF, IL-3 and M-CSF.
===Stages:===
====Monoblast====
This is the first stage after cell has differentiated into the [[Haematopoiesis - Overview#Colony Forming Units|CFU-M]].
====Promonocyte====
Cell has a large nucleus and basophilic cytoplasm and consists of two populations:- One rapidly dividing and the other slowly dividing, which acts as a reservoir.
====Monocyte====
Monocytes are incapable of mitosis and enter the circulation. They have a large kidney shaped nucleus with a slightly basophilic cytoplasm, which is often vacuolated.

====Macrophage====
Once the monocyte has entered tissue it differentiates into a macrophage.

===Dendritic cells===
These develop from the monoblast under the stimualtion of GM-CSF and IL-4 into an immature dendritic cell. This then develops into the mature [[T_cell_differentiation#Dendritic_Cells|dendritic cell]] under stimulation of TNF-α.
 

==Lymphopoiesis==
[[Lymphocytes - Introduction|Lymphocytes]] develop from the [[Haematopoiesis - Overview#Colony Forming Units|CFU-L]]'s. Those destined to become [[T cells]] leave the [[Bone Marrow - Anatomy & Physiology|bone marrow]] and migrate to the [[Thymus - Anatomy & Physiology|thymus]], and those destined to be [[B cells]] migrate to the [[Spleen - Anatomy & Physiology|spleen]] and gut-associated lymphoid tissue (GALT) or proliferate directly from the bone marrow.
{|cellpadding="5" cellspacing="1" border="1"
|
!style="background-color:#ffffcc"|B cell
!colspan="3" style="background-color:#e6e6fa"|T cell
|-align="center"
!rowspan="5"|Differentiation
|colspan="4"|CFU-L
|-align="center"
|style="background-color:#ffffcc"|▼Il-7 & Il-11
|colspan="3" style="background-color:#e6e6fa"|▼Il-7 & SCF
|-align="center"
|style="background-color:#ffffcc"|B lymphoid cell progenitor
|colspan="3" style="background-color:#e6e6fa"|T lymphoid cell progenitor
|-align="center"
|style="background-color:#ffffcc"|▼Il-3 & Il-7
|style="background-color:#e6e6fa"|▼Il-7
|style="background-color:#e6e6fa"|▼Il-2, IL-12 & Il-18
|style="background-color:#e6e6fa"|▼Il-3, Il-6, GM-CSF & SCF
|-align="center"
|style="background-color:#ffffcc"|Pre-B cell
|style="background-color:#e6e6fa"|Pre-T cell
|style="background-color:#e6e6fa"|Pre-NK cell
|style="background-color:#e6e6fa"|Pre-Dendritic cell
|-align="center"
!Maturationsite
|style="background-color:#ffffcc"|Bone marrow, spleen or GALTCloacal bursa (birds)
|style="background-color:#e6e6fa" colspan="3"|Thymus
|-align="center"
!Mature
|style="background-color:#ffffcc"|'''B cell'''▼(Antigen stim.)'''Plasma & Memory cell'''
|style="background-color:#e6e6fa"|'''T Cell'''HelperCytotoxicRegulatory
|style="background-color:#e6e6fa"|'''NK cell'''
|style="background-color:#e6e6fa"|'''Dendritic cell'''
|}
'''Note:'''
*Between the 'pre-[type] cell' stage and the final mature all the lymphocytes are referred to as 'immature [type] cells'.
* T cell differentiation into helper, cytotoxic and T cells with regulator functions is induced by Il-10 & TNF-γ
[[Category:Haematopoiesis]]

Leukopoiesis

2012-05-28T11:21:36Z

Rjfrancisrvc: /* Summary of pathways */

[[Image:Leukopoiesis pathway.jpg|right|thumb|400px|'''Leukopoiesis pathway''']]
==Introduction==
Leukopoiesis is the process of formation of [[Leukocytes|leukocytes]] (white blood cells) from stem cells in haematopoietic organs. Leukocytes develop from either multipotential myeloid stem cells ([[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]]) or multipotential lymphoid stem cells ([[Haematopoiesis - Overview#Colony Forming Units|CFU-L]]). 
Leukocytes developing from CFU-GEMM’s are granulocytes ([[Neutrophils|neutrophils]], [[Basophils| basophils]] and [[Eosinophils| eosinophils]]) or [[Monocytes|monocytes]].
Leukocytes developing from CFU-Ls are [[:Category:Lymphocytes|lymphocytes]] (T & B cells, dendritic and NK cells).

==Granulopoiesis==
All granulocytes develop from the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]] cells.
===Summary of pathways===
<div style="text-align: center;">
{| cellpadding="10" cellspacing="0" border="1" align="left"
|
!Monocyte
!Neutrophil
!Basophil
!Eosinophil
|rowspan="10"|[[Image:LH_Developing_granulocytes_Histology.jpg|200px|Developing granulocytes]]©RVC 2008
|-
!Stem cell
|colspan="4"|CFU-GEMM
|-
!CFU
|CFU-M
|CFU-G
|CFU-Ba
|CFU-Eo
|-
!Cytokines
|GM-CSFIL-3M-CSF
|GM-CSFIL-3G-CSF
|valign="top"|GM-CSFIL-3
|GM-CSFIL-3IL-5
|-
!Rowspan="6"|Stages
|Monoblast
|colspan="3"|Myelocyte
|-
|Promonocyte
|colspan="3"|Promyelocyte
|-
|rowspan="4"|Monocyte
|Neutrophilic Myelocyte
|Basophilic Myelocyte
|Eosinophilic Myelocyte
|-
|Neutrophilic Metamyelocyte
|rowspan="2"|Basophilic Metamyelocyte
|rowspan="2"|Eosinophilic Metamyelocyte
|-
|Band Cell
|-
|Neutrophil
|Basophil
|Eosinophil
|}
</div>
 

==Neutrophils==
Under the stimulation of [[Cytokines|cytokines]] GM-CSF, G-CSF and Il-3 the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]] differentiates into the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GM]], the common precursor for both neutrophils and monocytes. This then further differentiates into [[Haematopoiesis - Overview#Colony Forming Units|CFU-G]].
===Stages:===
====Myeloblast====
Large cell with a large nucleus and which demonstrates basophilic staining. This stage exists for all granulocytes.

====Promyelocyte====
During this stage primary (azurophilic) granules are formed. This stage exists for all granulocytes.

====Neutrophilic myelocyte====
The developing neutrophil can now be differentiated from basophils and eosinophils as neutrophil specific granules are now being formed.

====Neutrophilic metamyelocyte====
At this stage mitosis can no longer occur. The nucleus elongates, becomes heterochromatic and has a kidney like shape. Differentiation is now much clearer from other granulocytes as the specific granules are in a far greater number than the primary granules formed in the promyelocyte stage.

====Band cell====
Nucleus elongates further and represents a horse shoe. Nucleus starts to segment.
====Neutrophil====
Mature neutrophil is formed and the nucleus is segmented and has 3 to 5 lobes. This lobular structure of the nucleus gives rise to the name polymorphonuclear neutrophil.
 

==Basophils==
Under the stimulation of GM-CSF and Il-3, the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]] differentiates into [[Haematopoiesis - Overview#Colony Forming Units|CFU-Ba]].
===Stages:===
====Myeloblast & Promyelocyte====
These stages are common to all granulocytes and no distinction can be made between different cell lines.

====Basophilic myelocyte & metamyelocyte====
Specific granules start to appear in the myelocyte stage, and as the cell develops into the metamyelocyte stage, mitosis ceases.

====Basophil====
Final nuclear shape is masked by the high density of cytoplasmic granules.
 

==Eosinophils==
Under the stimulation of GM-CSF, Il-3 and Il-5 the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]] differentiates into the [[Haematopoiesis - Overview#Colony Forming Units|CFU-Eo]].
===Stages:===
====Myeloblast & Promyelocyte====
These stages are common to all granulocytes and no distinction can be made between different cell lines.

====Eosinophilic myelocyte & metamyelocyte====
Specific granules start to appear in the myelocyte stage and once the cell has reached the metamyelocyte stage it cannot undergo further mitosis.
====Eosinophil====
Mature cell has a bilobed nucleus. There are species specific variations in granule size once stained.
 

==Monocytes==
Monocytes develop from the same precursor as neutrophils - the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GM]]. This then differentiates into the [[Haematopoiesis - Overview#Colony Forming Units|CFU-M]] under the influence of GM-CSF, IL-3 and M-CSF.
===Stages:===
====Monoblast====
This is the first stage after cell has differentiated into the [[Haematopoiesis - Overview#Colony Forming Units|CFU-M]].
====Promonocyte====
Cell has a large nucleus and basophilic cytoplasm and consists of two populations:- One rapidly dividing and the other slowly dividing, which acts as a reservoir.
====Monocyte====
Monocytes are incapable of mitosis and enter the circulation. They have a large kidney shaped nucleus with a slightly basophilic cytoplasm, which is often vacuolated.

====Macrophage====
Once the monocyte has entered tissue it differentiates into a macrophage.

===Dendritic cells===
These develop from the monoblast under the stimualtion of GM-CSF and IL-4 into an immature dendritic cell. This then develops into the mature [[T_cell_differentiation#Dendritic_Cells|dendritic cell]] under stimulation of TNF-α.
 

==Lymphopoiesis==
[[Lymphocytes - Introduction|Lymphocytes]] develop from the [[Haematopoiesis - Overview#Colony Forming Units|CFU-L]]'s. Those destined to become [[T cells]] leave the [[Bone Marrow - Anatomy & Physiology|bone marrow]] and migrate to the [[Thymus - Anatomy & Physiology|thymus]], and those destined to be [[B cells]] migrate to the [[Spleen - Anatomy & Physiology|spleen]] and gut-associated lymphoid tissue (GALT) or proliferate directly from the bone marrow.
{|cellpadding="5" cellspacing="1" border="1"
|
!style="background-color:#ffffcc"|B cell
!colspan="3" style="background-color:#e6e6fa"|T cell
|-align="center"
!rowspan="5"|Differentiation
|colspan="4"|CFU-L
|-align="center"
|style="background-color:#ffffcc"|▼Il-7 & Il-11
|colspan="3" style="background-color:#e6e6fa"|▼Il-7 & SCF
|-align="center"
|style="background-color:#ffffcc"|B lymphoid cell progenitor
|colspan="3" style="background-color:#e6e6fa"|T lymphoid cell progenitor
|-align="center"
|style="background-color:#ffffcc"|▼Il-3 & Il-7
|style="background-color:#e6e6fa"|▼Il-7
|style="background-color:#e6e6fa"|▼Il-2, IL-12 & Il-18
|style="background-color:#e6e6fa"|▼Il-3, Il-6, GM-CSF & SCF
|-align="center"
|style="background-color:#ffffcc"|Pre-B cell
|style="background-color:#e6e6fa"|Pre-T cell
|style="background-color:#e6e6fa"|Pre-NK cell
|style="background-color:#e6e6fa"|Pre-Dendritic cell
|-align="center"
!Maturationsite
|style="background-color:#ffffcc"|Bone marrow, spleen or GALTCloacal bursa (birds)
|style="background-color:#e6e6fa" colspan="3"|Thymus
|-align="center"
!Mature
|style="background-color:#ffffcc"|'''B cell'''▼(Antigen stim.)'''Plasma & Memory cell'''
|style="background-color:#e6e6fa"|'''T Cell'''HelperCytotoxicRegulatory
|style="background-color:#e6e6fa"|'''NK cell'''
|style="background-color:#e6e6fa"|'''Dendritic cell'''
|}
'''Note:'''
*Between the 'pre-[type] cell' stage and the final mature all the lymphocytes are referred to as 'immature [type] cells'.
* T cell differentiation into helper, cytotoxic and T cells with regulator functions is induced by Il-10 & TNF-γ
[[Category:Haematopoiesis]]

Immunoglobulin E

2012-05-25T10:20:08Z

Rjfrancisrvc: /* Overview */

==Overview==
[[Image:LH IgE.png|thumb|250px|right|'''IgE''']]
[[Image:IgE.jpg|thumb|right|250px|IgE - B. Catchpole, RVC 2008]]

Commonly referred to as ''IgE''.

Unlike [[IgM]], [[IgG]] and [[IgA]], IgE does not function as a soluble antibody, with binding to Fcε receptors required before it can bind to the target antigen, and is found in low levels in blood plasma. Like [[IgA]], it is produced by [[B cell differentiation|plasma cells]] and is mainly localised to mucosal surfaces.

==Structure==

IgE is Y-shaped with heavy chain type ε, and exists as a monomer.

''Note: Janeway <ref>{{citation|initiallast = Janeway|initialfirst = C.A|2last = Travers|2first = P|3last = Walport|3first = M|finallast = Shlomchik|finalfirst = M.J|year = 2005|title = Immunobiology: The immune system in health and disease|ed = 6th |city = New York|pub = Garland Science Publishing|range = 156-157}}</ref> states that IgE has no hinge region whereas Tizard <ref>{{citation|initiallast = Tizard|initialfirst = I.R|year = 2004|title = Veterinary Immunology: An Introduction|ed = 7th|city = Philadelphia|pub = Saunders|range = 148-149}}</ref> indicates that it does.''

==Production==

It is produced when TH2 cells stimulate CD40 and produce IL-4 and IL-13, which causes B cell differentiation to plasma cells and class switching to IgE production.

==Function==

IgE triggers acute inflammation by binding to the FCεRI receptors on mast cells in the lamina propria and [[Basophils|basophils]], causing degranulation when bound to target. It is involved in [[Type I Hypersensitivity|type I hypersensitivity reactions]]. Cross-linking of IgE molecules by antigens, triggers [[Mast Cells|mast cell]] and [[Eosinophil|eosinophil]] degranulation and an inflammatory response. IgE has considerable involvement in producing [[Immunity to Parasites|immunity to parasitic worms]], particularly [[:Category:Nematodes|nematode]] parasites. It may mediate their expulsion or killing via mast cell activity, cytotoxic [[Eosinophils|eosinophils]], [[Macrophages|macrophages]], and so on.

==References==
<references />
 

==Links==

[[Immunoglobulins|Immunoglobulins]]

[[Immunoglobulin A|Immunoglobulin A]]

[[Immunoglobulin D|Immunoglobulin D]]

[[Immunoglobulin G|Immunoglobulin G]]

[[Immunoglobulin M|Immunoglobulin M]]
 
{{Jim Bee 2007}}
[[Category:Immunoglobulins]]
[[Category:A&P Done]]

Immunoglobulins - Overview

2012-05-25T10:18:17Z

Rjfrancisrvc: /* Immunoglobulin Class Switching */

{{review}}
[[Image:LH Antibody.png|thumb|200px|right|'''Immunoglobulin''' Je_at_uwo 2006, WikiMedia Commons]]
Also known as '''''antibodies
==Introduction==
''Also called antibodies''
Immunoglobulins (Ig) are the soluble form of B cell receptors (BCR) released by plasma cells after they have been activated. Immunoglobulins have to bind to a number of different antigens in a variety of environments and as such there are several different immunoglobulin classes. Each class has an optimum environment of action.
==Structure==
[[Image:LH Ig.png|thumb|200px|right|'''Immunoglobulin''' Asher Allison 2008]]

Antibodies are "Y-shaped" and consist of two identical heavy (H) chains and two identical light (L) chains with each H chain being linked to an L chain. The heavy chain consists of 4 or 5 protein domains, 1 amino terminal variable domain and 3 or 4 constant domains. Each light chain has one variable and one constant domain. Each arm of the molecule consists of one L chain and part of an H chain and there are two identical antigen-binding sites on each antibody molecule, one at the tip of each arm. The binding sites are made up of a combination of the variable domains of 1H and 1L, although single cells only have receptors of one specificity. The antigen binding site of an antibody is determined by a combination of the amino acid sequence of both the heavy and light chain variable domains (VH and VL). Antibodies of different specificities have different amino acids within one of three regions of the variable domains and these are called the hypervariable regions. The '''variable domains''' are '''folded''' in such a way as to form a pocket into which antigens fit. The '''constant domains''' do '''not''' bind antigen, although they determine the biological functions of the antibody molecules.
 
 
At the carboxyl terminus of B-cell expressed Ig is a region that holds the antibody molecule in the cell membrane. Secreted 'free' antibodies do not possess this region. The '''Fab''' fragments of the immunoglobulin is the '''antigen binding fragment''' generated from the light chains when digested by papain (proteolytic enzyme). The '''Fc''' fragment is the fragment produced by '''papain from the heavy chains''' and this fragment '''mediates [[Phagocytosis|phagocytosis]]''', triggers '''[[Inflammation|inflammation]]''', activates '''[[Complement|complement]]''' and '''targets Ig''' to certain tissues.

==Function==
[[Image:Ab-antigen.jpg|thumb|right|150px|Antibody binds 2 whole antigen molecules - B. Catchpole, RVC 2008]]
Antibodies form part of the adaptive immune response. For further information on the adaptive immune response, see [[:Category:Adaptive Immune System|here]]. All antibody classes bind antigen in a similar manner; the initial trigger for all antibody function is the association of antigen with the antigen-binding sites of the immunoglobulin molecules. However, different classes serve different physiological functions and functional differences between antibody classes are reflected in the structural differences in their '''heavy chain constant regions'''. These heavy chain regions comprise the '''effector domains''' of antibody molecules. In general antibodies have four major effector functions:
 
 
==='''Blockade and agglutination'''===
This action of antibody binding to antigen is a protective function. Antibody may bind to biologically active sites on toxins, inhibiting their binding sites. In a similar manner, antibody can bind the surface of viruses and prevent them from infecting cells. Antibody molecules are at least divalent, and many are greater than divalent which means that antibody can cross-link antibody forming an antibody '''agglutination'''. The ability to cross-link or agglutinate can be the primary function of the antibody. In order to be pathogenic, many micro-organisms must be able to contact viable host cells. If antibody molecules agglutinate these micro-organisms, any cell contact is prevented and the pathogenic effect is removed or reduced. The main biological function of '''[[Immunoglobulin A|IgA]]''' is to cross-link potentially pathogenic molecules.
 
 
==='''Promotion of phagocytosis'''===
Antibodies also have a function to facilitate [[Phagocytosis|phagocytosis]]. Phagocytes have receptors for the '''Fc''' portion of antibody, using '''Fc receptors (FcR)'''. FcR bind the Fc portion of antibody on antigen/antibody (Ag/Ab) complexes, although the antibody alone does not interact with FcR. Interaction of FcR with Ag/Ab complexes stimulates '''cellular activation''' which greatly increases the efficiency of phagocytosis. This process is called '''opsonisation'''. Opsonisation promotes the '''production of intracellular enzymes''' and therefore promotes the killing and digestion of internalised micro-organisms. Systems used by phagocytes that are important in intracellular killing include free radicals such as oxygen and chlorine, hydrogen peroxidase and nitric oxide produced by nitric oxide synthase. Ultimately phagocytes undergo '''degranulation''' resulting in the '''secretion of certain enzymes and cytotoxic molecules'''. These systems are also activated by the interferons, especially the immune interferon, interferon gamma (IFNγ). Antibody-mediated opsonisation of micro organisms is much more efficient that innate immune system receptors. Phagocytes also have receptors for iC3b, a [[Complement|complement]] component which is also a major initiator of opsonisation. Two particulary important phagocytic cells that have FcR are the [[Neutrophils|neutrophils]] and [[Macrophages|macrophages]].
 
 

==='''Degranulation of [[Mast Cells|mast cells]]/[[Eosinophils|eosinophils]]'''===
Antibodies play an important role in the [[Innate Immunity Cellular Responses|innate immune response]] to parasites. The Eosinophils and Mast Cells have FcR that are specific to IgE. When the IgE are cross-linked by antigen the eosinophils and Mast cells can interact with the IgE causing the release of their granules through the process known as exocytosis (granule fusion with the plasma membrane). The causes proteolytic enzyme release from eosinophils, and vasoactive peptide and cytokine release by Mast cells which then activates the innate immune response. Interestingly, this response is also responsible for the Type I hypersensitivity reaction.

==='''[[Complement|Complement fixation]]'''===
Cross-linking two Fc regions of IgM and IgG by complement component C1q begins the [[Complement| classical complement pathway]]. As IgM has '''five''' Fc regions it is a much better activator of complement than IgG (as IgG only has '''one''' Fc region).

==Classes==
There are five classes of Immunoglobulins, which vary due to the composition of their heavy chains. These are common across mammals but subclasses of them do vary between species. '''IgY''' is present in yolk.
{|style="border:3px solid;" cellpadding="0"
|width="150"|
!width="200"|[[IgA]]
!width="200"|[[IgD]]
!width="200"|[[IgE]]
!width="200"|[[IgG]]
!width="200"|[[IgM]]
|-align="middle"
!Weight (kDa)
|360
|180
|200
|180
|900
|-align="middle"
!No. subunits
|2
|1
|1
|1
|5
|-align="middle"
!Heavy chain
|α
|δ
|ε
|γ
|µ
|-align="middle"
!Mainsite of production
|Alimentary/Respiratory tracts
|Spleen/Lymph nodes
|Alimentary/Respiratory tracts
|Spleen/Lymph nodes
|Spleen/Lymph nodes
|}

==Variation==
===Subclasses===
Subclasses of the five major classes also exist. These occur in the '''heavy chains''' and are coded for by the IGH gene. For examples horses have six subclasses of the [[IgG]] immunoglobulin coded for by the genes IGHG1→ IGHG6 while cattle and sheep only have three subclasses (IGHG1→ IGHG3). Therefore within the [[IgG]] class there are '''several subclasses depending on the species'''. Humans and rodents have four [[IgG]] subclasses, dogs have three subclasses, ruminants have two or three subclasses and in some species there are also two IgA subclasses. Antibody specificity is unrelated to class. Different classes of antibody can be associated with the same V domains and have the same specificity. It is possible for a single B-cell to produce antibody of one specificity but two or more classes. A mature B-cell has the genetic capacity to produce antibody of all classes and subclasses but of one specificity only.
 
 
===Allo & Idiotypes===
Allotypes are differences in immunoglobulins between individuals of a particular species. They are inheritable. Idiotypes are variations in the sequences of amino acids in the variable regions of the light and heavy chains.
 
 
===Immunoglobulin Class Switching===
Different classes of antibody differ from each other in size, charge, amino acid composition, associated carbohydrate and function. Immunoglobulin heavy and light chains are encoded by separate genes with the first 300 bases of each gene encoding the variable part of each protein chain. The combination of the VH and VL contribute to the antigenic specificity and any individual has the capability of producing over 100 million different antibody specificities. The rest of the antibody gene encodes all the constant domains. There are five different types of heavy chain constant domains - μ, γ, ε, α. Different heavy chains are associated with different classes of antibody;
 
* '''μ chain - [[IgM]] '''
* '''γ chain -[[IgG]]'''
* '''ε chain - [[IgE]]'''
* '''α chain - [[IgA]]'''
 
In humans and mice there exists a fifth Ig class, '''[[IgD]] (δ chain)'''. IgD is always expressed on B-cell membranes with [[IgM]] but is ''never secreted''. The sequence of constant region genes on the chromosome is M, G, E and A. In humans/ rodents the Cδ ([[IgD]]) is immediately downstream of the M gene and prior to antigenic stimulation, B-cells express cell membrane-associated [[IgM]].
 
 
The first immunoglobulin produced during an immune response is '''always [[IgM]]''' because the Cμ gene is the first constant H chain gene downstream of the variable domain. After antigenic exposure the [[IgM]]+ B-cells differentiate and begin to synthesise other classes of immunoglobulin, but only under the '''direct influence of a T-cell'''. This system is known as '''immunoglobulin heavy chain switching'''. The [[IgG]] antibodies produced in both primary and secondary responses originate from the same clones of B-cells as the [[IgM]] antibodies. The different antibody classes have the same variable domain combinations, and therefore the same antigenic specificity. Under the influence of T-cells, B-cells undergo immunoglobulin heavy chain switching and the B-cells mature from [[IgM]] to [[IgG]] producers, with [[IgE]] and [[IgA]] producers generated under certain immune responses. These immunoglobulins (IgA and IgE) tend to be produced within lymphoid tissue associated with mucosal surfaces.
 
 

==Clinical Uses==
[[Vaccines|Vaccination]]

[[Immunological Testing]]

{{Template:Learning
|flashcards = [[Immunoglobulins Flashcards]]
}}

==Links==
'''Websites'''
*http://www.cellsalive.com
 
{{Jim Bee 2007}}
[[Category:Immunoglobulins|A]]
[[Category:A&P Done]]

Immunoglobulins - Overview

2012-05-25T10:15:16Z

Rjfrancisrvc: /* Immunoglobulin Class Switching */

{{review}}
[[Image:LH Antibody.png|thumb|200px|right|'''Immunoglobulin''' Je_at_uwo 2006, WikiMedia Commons]]
Also known as '''''antibodies
==Introduction==
''Also called antibodies''
Immunoglobulins (Ig) are the soluble form of B cell receptors (BCR) released by plasma cells after they have been activated. Immunoglobulins have to bind to a number of different antigens in a variety of environments and as such there are several different immunoglobulin classes. Each class has an optimum environment of action.
==Structure==
[[Image:LH Ig.png|thumb|200px|right|'''Immunoglobulin''' Asher Allison 2008]]

Antibodies are "Y-shaped" and consist of two identical heavy (H) chains and two identical light (L) chains with each H chain being linked to an L chain. The heavy chain consists of 4 or 5 protein domains, 1 amino terminal variable domain and 3 or 4 constant domains. Each light chain has one variable and one constant domain. Each arm of the molecule consists of one L chain and part of an H chain and there are two identical antigen-binding sites on each antibody molecule, one at the tip of each arm. The binding sites are made up of a combination of the variable domains of 1H and 1L, although single cells only have receptors of one specificity. The antigen binding site of an antibody is determined by a combination of the amino acid sequence of both the heavy and light chain variable domains (VH and VL). Antibodies of different specificities have different amino acids within one of three regions of the variable domains and these are called the hypervariable regions. The '''variable domains''' are '''folded''' in such a way as to form a pocket into which antigens fit. The '''constant domains''' do '''not''' bind antigen, although they determine the biological functions of the antibody molecules.
 
 
At the carboxyl terminus of B-cell expressed Ig is a region that holds the antibody molecule in the cell membrane. Secreted 'free' antibodies do not possess this region. The '''Fab''' fragments of the immunoglobulin is the '''antigen binding fragment''' generated from the light chains when digested by papain (proteolytic enzyme). The '''Fc''' fragment is the fragment produced by '''papain from the heavy chains''' and this fragment '''mediates [[Phagocytosis|phagocytosis]]''', triggers '''[[Inflammation|inflammation]]''', activates '''[[Complement|complement]]''' and '''targets Ig''' to certain tissues.

==Function==
[[Image:Ab-antigen.jpg|thumb|right|150px|Antibody binds 2 whole antigen molecules - B. Catchpole, RVC 2008]]
Antibodies form part of the adaptive immune response. For further information on the adaptive immune response, see [[:Category:Adaptive Immune System|here]]. All antibody classes bind antigen in a similar manner; the initial trigger for all antibody function is the association of antigen with the antigen-binding sites of the immunoglobulin molecules. However, different classes serve different physiological functions and functional differences between antibody classes are reflected in the structural differences in their '''heavy chain constant regions'''. These heavy chain regions comprise the '''effector domains''' of antibody molecules. In general antibodies have four major effector functions:
 
 
==='''Blockade and agglutination'''===
This action of antibody binding to antigen is a protective function. Antibody may bind to biologically active sites on toxins, inhibiting their binding sites. In a similar manner, antibody can bind the surface of viruses and prevent them from infecting cells. Antibody molecules are at least divalent, and many are greater than divalent which means that antibody can cross-link antibody forming an antibody '''agglutination'''. The ability to cross-link or agglutinate can be the primary function of the antibody. In order to be pathogenic, many micro-organisms must be able to contact viable host cells. If antibody molecules agglutinate these micro-organisms, any cell contact is prevented and the pathogenic effect is removed or reduced. The main biological function of '''[[Immunoglobulin A|IgA]]''' is to cross-link potentially pathogenic molecules.
 
 
==='''Promotion of phagocytosis'''===
Antibodies also have a function to facilitate [[Phagocytosis|phagocytosis]]. Phagocytes have receptors for the '''Fc''' portion of antibody, using '''Fc receptors (FcR)'''. FcR bind the Fc portion of antibody on antigen/antibody (Ag/Ab) complexes, although the antibody alone does not interact with FcR. Interaction of FcR with Ag/Ab complexes stimulates '''cellular activation''' which greatly increases the efficiency of phagocytosis. This process is called '''opsonisation'''. Opsonisation promotes the '''production of intracellular enzymes''' and therefore promotes the killing and digestion of internalised micro-organisms. Systems used by phagocytes that are important in intracellular killing include free radicals such as oxygen and chlorine, hydrogen peroxidase and nitric oxide produced by nitric oxide synthase. Ultimately phagocytes undergo '''degranulation''' resulting in the '''secretion of certain enzymes and cytotoxic molecules'''. These systems are also activated by the interferons, especially the immune interferon, interferon gamma (IFNγ). Antibody-mediated opsonisation of micro organisms is much more efficient that innate immune system receptors. Phagocytes also have receptors for iC3b, a [[Complement|complement]] component which is also a major initiator of opsonisation. Two particulary important phagocytic cells that have FcR are the [[Neutrophils|neutrophils]] and [[Macrophages|macrophages]].
 
 

==='''Degranulation of [[Mast Cells|mast cells]]/[[Eosinophils|eosinophils]]'''===
Antibodies play an important role in the [[Innate Immunity Cellular Responses|innate immune response]] to parasites. The Eosinophils and Mast Cells have FcR that are specific to IgE. When the IgE are cross-linked by antigen the eosinophils and Mast cells can interact with the IgE causing the release of their granules through the process known as exocytosis (granule fusion with the plasma membrane). The causes proteolytic enzyme release from eosinophils, and vasoactive peptide and cytokine release by Mast cells which then activates the innate immune response. Interestingly, this response is also responsible for the Type I hypersensitivity reaction.

==='''[[Complement|Complement fixation]]'''===
Cross-linking two Fc regions of IgM and IgG by complement component C1q begins the [[Complement| classical complement pathway]]. As IgM has '''five''' Fc regions it is a much better activator of complement than IgG (as IgG only has '''one''' Fc region).

==Classes==
There are five classes of Immunoglobulins, which vary due to the composition of their heavy chains. These are common across mammals but subclasses of them do vary between species. '''IgY''' is present in yolk.
{|style="border:3px solid;" cellpadding="0"
|width="150"|
!width="200"|[[IgA]]
!width="200"|[[IgD]]
!width="200"|[[IgE]]
!width="200"|[[IgG]]
!width="200"|[[IgM]]
|-align="middle"
!Weight (kDa)
|360
|180
|200
|180
|900
|-align="middle"
!No. subunits
|2
|1
|1
|1
|5
|-align="middle"
!Heavy chain
|α
|δ
|ε
|γ
|µ
|-align="middle"
!Mainsite of production
|Alimentary/Respiratory tracts
|Spleen/Lymph nodes
|Alimentary/Respiratory tracts
|Spleen/Lymph nodes
|Spleen/Lymph nodes
|}

==Variation==
===Subclasses===
Subclasses of the five major classes also exist. These occur in the '''heavy chains''' and are coded for by the IGH gene. For examples horses have six subclasses of the [[IgG]] immunoglobulin coded for by the genes IGHG1→ IGHG6 while cattle and sheep only have three subclasses (IGHG1→ IGHG3). Therefore within the [[IgG]] class there are '''several subclasses depending on the species'''. Humans and rodents have four [[IgG]] subclasses, dogs have three subclasses, ruminants have two or three subclasses and in some species there are also two IgA subclasses. Antibody specificity is unrelated to class. Different classes of antibody can be associated with the same V domains and have the same specificity. It is possible for a single B-cell to produce antibody of one specificity but two or more classes. A mature B-cell has the genetic capacity to produce antibody of all classes and subclasses but of one specificity only.
 
 
===Allo & Idiotypes===
Allotypes are differences in immunoglobulins between individuals of a particular species. They are inheritable. Idiotypes are variations in the sequences of amino acids in the variable regions of the light and heavy chains.
 
 
===Immunoglobulin Class Switching===
Different classes of antibody differ from each other in size, charge, amino acid composition, associated carbohydrate and function. Immunoglobulin heavy and light chains are encoded by separate genes with the first 300 bases of each gene encoding the variable part of each protein chain. The combination of the VH and VL contribute to the antigenic specificity and any individual has the capability of producing over 100 million different antibody specificities. The rest of the antibody gene encodes all the constant domains. There are five different types of heavy chain constant domains - μ, γ, ε, α. Different heavy chains are associated with different classes of antibody;
 
* '''μ chain - [[IgM]] '''
* '''γ chain -[[IgG]]'''
* '''ε chain - [[IgE]]'''
* '''α chain - [[IgA]]'''
 
In humans and mice there exists a fifth Ig class, '''[[IgD]] (δ chain)'''. IgD is always expressed on B-cell membranes with [[IgM]] but is ''never secreted''. The sequence of constant region genes on the chromosome is M, G, E and A. In humans/ rodents the Cδ ([[IgD]]) is immediately downstream of the M gene and prior to antigenic stimulation, B-cells express cell membrane-associated [[IgM]].
 
 
The first immunoglobulin produced during an immune response is '''always [[IgM]]''' because the Cμ gene is the first constant H chain gene downstream of the variable domain. After antigenic exposure the [[IgM]]+ B-cells differentiate and begin to synthesise other classes of immunoglobulin, but only under the '''direct influence of a T-cell'''. This system is known as '''immunoglobulin heavy chain switching'''. The [[IgG]] antibodies produced in both primary and secondary responses originate from the same clones of B-cells as the [[IgM]] antibodies. The different antibody classes have the same variable domain combinations, and therefore the same antigenic specificity. Under the influence of T-cells, B-cells undergo immunoglobulin heavy chain switching and the B-cells mature from [[IgM]] to [[IgG]] producers and IgE and IgA producers can also be generated. These immunoglobulins tend to be produced within lymphoid tissue associated with mucosal surfaces.
 
 

==Clinical Uses==
[[Vaccines|Vaccination]]

[[Immunological Testing]]

{{Template:Learning
|flashcards = [[Immunoglobulins Flashcards]]
}}

==Links==
'''Websites'''
*http://www.cellsalive.com
 
{{Jim Bee 2007}}
[[Category:Immunoglobulins|A]]
[[Category:A&P Done]]

Immunoglobulins - Overview

2012-05-25T10:13:57Z

Rjfrancisrvc: /* Immunoglobulin Class Switching */

{{review}}
[[Image:LH Antibody.png|thumb|200px|right|'''Immunoglobulin''' Je_at_uwo 2006, WikiMedia Commons]]
Also known as '''''antibodies
==Introduction==
''Also called antibodies''
Immunoglobulins (Ig) are the soluble form of B cell receptors (BCR) released by plasma cells after they have been activated. Immunoglobulins have to bind to a number of different antigens in a variety of environments and as such there are several different immunoglobulin classes. Each class has an optimum environment of action.
==Structure==
[[Image:LH Ig.png|thumb|200px|right|'''Immunoglobulin''' Asher Allison 2008]]

Antibodies are "Y-shaped" and consist of two identical heavy (H) chains and two identical light (L) chains with each H chain being linked to an L chain. The heavy chain consists of 4 or 5 protein domains, 1 amino terminal variable domain and 3 or 4 constant domains. Each light chain has one variable and one constant domain. Each arm of the molecule consists of one L chain and part of an H chain and there are two identical antigen-binding sites on each antibody molecule, one at the tip of each arm. The binding sites are made up of a combination of the variable domains of 1H and 1L, although single cells only have receptors of one specificity. The antigen binding site of an antibody is determined by a combination of the amino acid sequence of both the heavy and light chain variable domains (VH and VL). Antibodies of different specificities have different amino acids within one of three regions of the variable domains and these are called the hypervariable regions. The '''variable domains''' are '''folded''' in such a way as to form a pocket into which antigens fit. The '''constant domains''' do '''not''' bind antigen, although they determine the biological functions of the antibody molecules.
 
 
At the carboxyl terminus of B-cell expressed Ig is a region that holds the antibody molecule in the cell membrane. Secreted 'free' antibodies do not possess this region. The '''Fab''' fragments of the immunoglobulin is the '''antigen binding fragment''' generated from the light chains when digested by papain (proteolytic enzyme). The '''Fc''' fragment is the fragment produced by '''papain from the heavy chains''' and this fragment '''mediates [[Phagocytosis|phagocytosis]]''', triggers '''[[Inflammation|inflammation]]''', activates '''[[Complement|complement]]''' and '''targets Ig''' to certain tissues.

==Function==
[[Image:Ab-antigen.jpg|thumb|right|150px|Antibody binds 2 whole antigen molecules - B. Catchpole, RVC 2008]]
Antibodies form part of the adaptive immune response. For further information on the adaptive immune response, see [[:Category:Adaptive Immune System|here]]. All antibody classes bind antigen in a similar manner; the initial trigger for all antibody function is the association of antigen with the antigen-binding sites of the immunoglobulin molecules. However, different classes serve different physiological functions and functional differences between antibody classes are reflected in the structural differences in their '''heavy chain constant regions'''. These heavy chain regions comprise the '''effector domains''' of antibody molecules. In general antibodies have four major effector functions:
 
 
==='''Blockade and agglutination'''===
This action of antibody binding to antigen is a protective function. Antibody may bind to biologically active sites on toxins, inhibiting their binding sites. In a similar manner, antibody can bind the surface of viruses and prevent them from infecting cells. Antibody molecules are at least divalent, and many are greater than divalent which means that antibody can cross-link antibody forming an antibody '''agglutination'''. The ability to cross-link or agglutinate can be the primary function of the antibody. In order to be pathogenic, many micro-organisms must be able to contact viable host cells. If antibody molecules agglutinate these micro-organisms, any cell contact is prevented and the pathogenic effect is removed or reduced. The main biological function of '''[[Immunoglobulin A|IgA]]''' is to cross-link potentially pathogenic molecules.
 
 
==='''Promotion of phagocytosis'''===
Antibodies also have a function to facilitate [[Phagocytosis|phagocytosis]]. Phagocytes have receptors for the '''Fc''' portion of antibody, using '''Fc receptors (FcR)'''. FcR bind the Fc portion of antibody on antigen/antibody (Ag/Ab) complexes, although the antibody alone does not interact with FcR. Interaction of FcR with Ag/Ab complexes stimulates '''cellular activation''' which greatly increases the efficiency of phagocytosis. This process is called '''opsonisation'''. Opsonisation promotes the '''production of intracellular enzymes''' and therefore promotes the killing and digestion of internalised micro-organisms. Systems used by phagocytes that are important in intracellular killing include free radicals such as oxygen and chlorine, hydrogen peroxidase and nitric oxide produced by nitric oxide synthase. Ultimately phagocytes undergo '''degranulation''' resulting in the '''secretion of certain enzymes and cytotoxic molecules'''. These systems are also activated by the interferons, especially the immune interferon, interferon gamma (IFNγ). Antibody-mediated opsonisation of micro organisms is much more efficient that innate immune system receptors. Phagocytes also have receptors for iC3b, a [[Complement|complement]] component which is also a major initiator of opsonisation. Two particulary important phagocytic cells that have FcR are the [[Neutrophils|neutrophils]] and [[Macrophages|macrophages]].
 
 

==='''Degranulation of [[Mast Cells|mast cells]]/[[Eosinophils|eosinophils]]'''===
Antibodies play an important role in the [[Innate Immunity Cellular Responses|innate immune response]] to parasites. The Eosinophils and Mast Cells have FcR that are specific to IgE. When the IgE are cross-linked by antigen the eosinophils and Mast cells can interact with the IgE causing the release of their granules through the process known as exocytosis (granule fusion with the plasma membrane). The causes proteolytic enzyme release from eosinophils, and vasoactive peptide and cytokine release by Mast cells which then activates the innate immune response. Interestingly, this response is also responsible for the Type I hypersensitivity reaction.

==='''[[Complement|Complement fixation]]'''===
Cross-linking two Fc regions of IgM and IgG by complement component C1q begins the [[Complement| classical complement pathway]]. As IgM has '''five''' Fc regions it is a much better activator of complement than IgG (as IgG only has '''one''' Fc region).

==Classes==
There are five classes of Immunoglobulins, which vary due to the composition of their heavy chains. These are common across mammals but subclasses of them do vary between species. '''IgY''' is present in yolk.
{|style="border:3px solid;" cellpadding="0"
|width="150"|
!width="200"|[[IgA]]
!width="200"|[[IgD]]
!width="200"|[[IgE]]
!width="200"|[[IgG]]
!width="200"|[[IgM]]
|-align="middle"
!Weight (kDa)
|360
|180
|200
|180
|900
|-align="middle"
!No. subunits
|2
|1
|1
|1
|5
|-align="middle"
!Heavy chain
|α
|δ
|ε
|γ
|µ
|-align="middle"
!Mainsite of production
|Alimentary/Respiratory tracts
|Spleen/Lymph nodes
|Alimentary/Respiratory tracts
|Spleen/Lymph nodes
|Spleen/Lymph nodes
|}

==Variation==
===Subclasses===
Subclasses of the five major classes also exist. These occur in the '''heavy chains''' and are coded for by the IGH gene. For examples horses have six subclasses of the [[IgG]] immunoglobulin coded for by the genes IGHG1→ IGHG6 while cattle and sheep only have three subclasses (IGHG1→ IGHG3). Therefore within the [[IgG]] class there are '''several subclasses depending on the species'''. Humans and rodents have four [[IgG]] subclasses, dogs have three subclasses, ruminants have two or three subclasses and in some species there are also two IgA subclasses. Antibody specificity is unrelated to class. Different classes of antibody can be associated with the same V domains and have the same specificity. It is possible for a single B-cell to produce antibody of one specificity but two or more classes. A mature B-cell has the genetic capacity to produce antibody of all classes and subclasses but of one specificity only.
 
 
===Allo & Idiotypes===
Allotypes are differences in immunoglobulins between individuals of a particular species. They are inheritable. Idiotypes are variations in the sequences of amino acids in the variable regions of the light and heavy chains.
 
 
===Immunoglobulin Class Switching===
Different classes of antibody differ from each other in size, charge, amino acid composition, associated carbohydrate and function. Immunoglobulin heavy and light chains are encoded by separate genes with the first 300 bases of each gene encoding the variable part of each protein chain. The combination of the VH and VL contribute to the antigenic specificity and any individual has the capability of producing over 100 million different antibody specificities. The rest of the antibody gene encodes all the constant domains. There are five different types of heavy chain constant domains - μ, γ, ε, α. Different heavy chains are associated with different classes of antibody;
 
* '''μ chain - [[IgM]] '''
* '''γ chain -[[IgG]]'''
* '''ε chain - [[IgE]]'''
* '''α chain - [[IgA]]'''
 
In humans and mice there exists a fifth Ig class, '''[[IgD]] (δ chain)'''. IgD is always expressed on B-cell membranes with [[IgM]] but is ''never secreted''. The sequence of constant region genes on the chromosome is M, G, E and A. In humans/ rodents the Cδ ([[IgD]]) is immediately downstream of the M gene and prior to antigenic stimulation, B-cells express cell membrane-associated [[IgM]]. The first immunoglobulin produced during an immune response is '''always [[IgM]]''' because the Cμ gene is the first constant H chain gene downstream of the variable domain. After antigenic exposure the [[IgM]]+ B-cells differentiate and begin to synthesise other classes of immunoglobulin, but only under the '''direct influence of a T-cell'''. This system is known as '''immunoglobulin heavy chain switching'''. The [[IgG]] antibodies produced in both primary and secondary responses originate from the same clones of B-cells as the [[IgM]] antibodies. The different antibody classes have the same variable domain combinations, and therefore the same antigenic specificity. Under the influence of T-cells, B-cells undergo immunoglobulin heavy chain switching and the B-cells mature from [[IgM]] to [[IgG]] producers and IgE and IgA producers can also be generated. These immunoglobulins tend to be produced within lymphoid tissue associated with mucosal surfaces.
 
 

==Clinical Uses==
[[Vaccines|Vaccination]]

[[Immunological Testing]]

{{Template:Learning
|flashcards = [[Immunoglobulins Flashcards]]
}}

==Links==
'''Websites'''
*http://www.cellsalive.com
 
{{Jim Bee 2007}}
[[Category:Immunoglobulins|A]]
[[Category:A&P Done]]

Immunoglobulin M

2012-05-25T10:11:18Z

Rjfrancisrvc: /* Production */

{{review}}
''Shortened to IgM''
[[Image:LH IgM.png|thumb|150px|right|'''IgM'''1 = IgM monomer2 = Heavy chains3 = Light chains4 =J chain5 = Disulfide bonds]]
[[Image:IgM.jpg|thumb|right|150px|IgM - B. Catchpole, RVC 2008]]
==Overview==
Is found in high concentrations in blood plasma (below [[IgG]] conc.) and is the major Ig produced, by [[B cell differentiation|plasma cells]], during the primary immune response

==Structure==
IgM is the primordial antibody and, although a monomer, is secreted as a pentamer (five monomers joined by disulphide bonds with two monomers joined by a J chain). This gives it ten identical antigen binding sites although IgM usually has relatively low affinity for its antigen. Its heavy chain is type mu (µ).

==Production==
Produced by plasma cells in the spleen, bone marrow and lymph nodes. Since it is around five times larger than "normal" antibody it does not diffuse quickly or enter tissues readily and as such its concentration in extracellular fluid and lymph is very low. It does not cross the placenta even in animals with haemochorial placentas e.g. apes. 
IgM is the first class of antibody produced by plasma cells, with production replaced by either [[IgG]] or [[IgE]] in a process known as '''[[Immunoglobulins - Overview|class-switching]]''' once the secondary immune response is initiated. 

==Function==

IgM mainly functions as a target for [[Complement|complement]] activation as well as roles in agglutination, opsonisation and virus neutralisation.
 
----
<center>[[Immunoglobulins|Immunoglobulins]]: [[Immunoglobulin A|Immunoglobulin A]], [[Immunoglobulin D|Immunoglobulin D]], [[Immunoglobulin E|Immunoglobulin E]], [[Immunoglobulin G|Immunoglobulin G]] & [[Immunoglobulin M|Immunoglobulin M]]</center>

 
{{Jim Bee 2007}}
[[Category:Immunoglobulins]]
[[Category:A&P Done]]

Immunoglobulin M

2012-05-25T10:10:57Z

Rjfrancisrvc: /* Production */

{{review}}
''Shortened to IgM''
[[Image:LH IgM.png|thumb|150px|right|'''IgM'''1 = IgM monomer2 = Heavy chains3 = Light chains4 =J chain5 = Disulfide bonds]]
[[Image:IgM.jpg|thumb|right|150px|IgM - B. Catchpole, RVC 2008]]
==Overview==
Is found in high concentrations in blood plasma (below [[IgG]] conc.) and is the major Ig produced, by [[B cell differentiation|plasma cells]], during the primary immune response

==Structure==
IgM is the primordial antibody and, although a monomer, is secreted as a pentamer (five monomers joined by disulphide bonds with two monomers joined by a J chain). This gives it ten identical antigen binding sites although IgM usually has relatively low affinity for its antigen. Its heavy chain is type mu (µ).

==Production==
Produced by plasma cells in the spleen, bone marrow and lymph nodes. Since it is around five times larger than "normal" antibody it does not diffuse quickly or enter tissues readily and as such its concentration in extracellular fluid and lymph is very low. It does not cross the placenta even in animals with haemochorial placentas e.g. apes. 
IgM is the first class of antibody produced by plasma cells, with production replaced by either [[IgG]] or [[IgE]] in a process known as '''[[Immunoglobulins - Overview
|class-switching]]''' once the secondary immune response is initiated 

==Function==

IgM mainly functions as a target for [[Complement|complement]] activation as well as roles in agglutination, opsonisation and virus neutralisation.
 
----
<center>[[Immunoglobulins|Immunoglobulins]]: [[Immunoglobulin A|Immunoglobulin A]], [[Immunoglobulin D|Immunoglobulin D]], [[Immunoglobulin E|Immunoglobulin E]], [[Immunoglobulin G|Immunoglobulin G]] & [[Immunoglobulin M|Immunoglobulin M]]</center>

 
{{Jim Bee 2007}}
[[Category:Immunoglobulins]]
[[Category:A&P Done]]

Immunoglobulin M

2012-05-25T10:10:38Z

Rjfrancisrvc: /* Production */

{{review}}
''Shortened to IgM''
[[Image:LH IgM.png|thumb|150px|right|'''IgM'''1 = IgM monomer2 = Heavy chains3 = Light chains4 =J chain5 = Disulfide bonds]]
[[Image:IgM.jpg|thumb|right|150px|IgM - B. Catchpole, RVC 2008]]
==Overview==
Is found in high concentrations in blood plasma (below [[IgG]] conc.) and is the major Ig produced, by [[B cell differentiation|plasma cells]], during the primary immune response

==Structure==
IgM is the primordial antibody and, although a monomer, is secreted as a pentamer (five monomers joined by disulphide bonds with two monomers joined by a J chain). This gives it ten identical antigen binding sites although IgM usually has relatively low affinity for its antigen. Its heavy chain is type mu (µ).

==Production==
Produced by plasma cells in the spleen, bone marrow and lymph nodes. Since it is around five times larger than "normal" antibody it does not diffuse quickly or enter tissues readily and as such its concentration in extracellular fluid and lymph is very low. It does not cross the placenta even in animals with haemochorial placentas e.g. apes. 
IgM is the first class of antibody produced by plasma cells, with production replaced by either [[IgG]] or [[IgE]] in a process known as '''[[Immunoglobulins -Overview|class-switching]]''' once the secondary immune response is initiated 

==Function==

IgM mainly functions as a target for [[Complement|complement]] activation as well as roles in agglutination, opsonisation and virus neutralisation.
 
----
<center>[[Immunoglobulins|Immunoglobulins]]: [[Immunoglobulin A|Immunoglobulin A]], [[Immunoglobulin D|Immunoglobulin D]], [[Immunoglobulin E|Immunoglobulin E]], [[Immunoglobulin G|Immunoglobulin G]] & [[Immunoglobulin M|Immunoglobulin M]]</center>

 
{{Jim Bee 2007}}
[[Category:Immunoglobulins]]
[[Category:A&P Done]]

Immunoglobulin M

2012-05-25T10:10:05Z

Rjfrancisrvc: /* Production */

{{review}}
''Shortened to IgM''
[[Image:LH IgM.png|thumb|150px|right|'''IgM'''1 = IgM monomer2 = Heavy chains3 = Light chains4 =J chain5 = Disulfide bonds]]
[[Image:IgM.jpg|thumb|right|150px|IgM - B. Catchpole, RVC 2008]]
==Overview==
Is found in high concentrations in blood plasma (below [[IgG]] conc.) and is the major Ig produced, by [[B cell differentiation|plasma cells]], during the primary immune response

==Structure==
IgM is the primordial antibody and, although a monomer, is secreted as a pentamer (five monomers joined by disulphide bonds with two monomers joined by a J chain). This gives it ten identical antigen binding sites although IgM usually has relatively low affinity for its antigen. Its heavy chain is type mu (µ).

==Production==
Produced by plasma cells in the spleen, bone marrow and lymph nodes. Since it is around five times larger than "normal" antibody it does not diffuse quickly or enter tissues readily and as such its concentration in extracellular fluid and lymph is very low. It does not cross the placenta even in animals with haemochorial placentas e.g. apes. 
IgM is the first class of antibody produced by plasma cells, with production replaced by either [[IgG]] or [[IgE]] in a process known as '''[[Immunoglobulin-Overview|class-switching]]''' once the secondary immune response is initiated 

==Function==

IgM mainly functions as a target for [[Complement|complement]] activation as well as roles in agglutination, opsonisation and virus neutralisation.
 
----
<center>[[Immunoglobulins|Immunoglobulins]]: [[Immunoglobulin A|Immunoglobulin A]], [[Immunoglobulin D|Immunoglobulin D]], [[Immunoglobulin E|Immunoglobulin E]], [[Immunoglobulin G|Immunoglobulin G]] & [[Immunoglobulin M|Immunoglobulin M]]</center>

 
{{Jim Bee 2007}}
[[Category:Immunoglobulins]]
[[Category:A&P Done]]

Immunoglobulin M

2012-05-25T10:09:54Z

Rjfrancisrvc: /* Production */

{{review}}
''Shortened to IgM''
[[Image:LH IgM.png|thumb|150px|right|'''IgM'''1 = IgM monomer2 = Heavy chains3 = Light chains4 =J chain5 = Disulfide bonds]]
[[Image:IgM.jpg|thumb|right|150px|IgM - B. Catchpole, RVC 2008]]
==Overview==
Is found in high concentrations in blood plasma (below [[IgG]] conc.) and is the major Ig produced, by [[B cell differentiation|plasma cells]], during the primary immune response

==Structure==
IgM is the primordial antibody and, although a monomer, is secreted as a pentamer (five monomers joined by disulphide bonds with two monomers joined by a J chain). This gives it ten identical antigen binding sites although IgM usually has relatively low affinity for its antigen. Its heavy chain is type mu (µ).

==Production==
Produced by plasma cells in the spleen, bone marrow and lymph nodes. Since it is around five times larger than "normal" antibody it does not diffuse quickly or enter tissues readily and as such its concentration in extracellular fluid and lymph is very low. It does not cross the placenta even in animals with haemochorial placentas e.g. apes. 
IgM is the first class of antibody produced by plasma cells, with production replaced by either [[IgG]] or [[IgE]] in a process known as '''[[Immunoglobulin Overview|class-switching]]''' once the secondary immune response is initiated 

==Function==

IgM mainly functions as a target for [[Complement|complement]] activation as well as roles in agglutination, opsonisation and virus neutralisation.
 
----
<center>[[Immunoglobulins|Immunoglobulins]]: [[Immunoglobulin A|Immunoglobulin A]], [[Immunoglobulin D|Immunoglobulin D]], [[Immunoglobulin E|Immunoglobulin E]], [[Immunoglobulin G|Immunoglobulin G]] & [[Immunoglobulin M|Immunoglobulin M]]</center>

 
{{Jim Bee 2007}}
[[Category:Immunoglobulins]]
[[Category:A&P Done]]

Immunoglobulin M

2012-05-25T10:09:38Z

Rjfrancisrvc: /* Production */

{{review}}
''Shortened to IgM''
[[Image:LH IgM.png|thumb|150px|right|'''IgM'''1 = IgM monomer2 = Heavy chains3 = Light chains4 =J chain5 = Disulfide bonds]]
[[Image:IgM.jpg|thumb|right|150px|IgM - B. Catchpole, RVC 2008]]
==Overview==
Is found in high concentrations in blood plasma (below [[IgG]] conc.) and is the major Ig produced, by [[B cell differentiation|plasma cells]], during the primary immune response

==Structure==
IgM is the primordial antibody and, although a monomer, is secreted as a pentamer (five monomers joined by disulphide bonds with two monomers joined by a J chain). This gives it ten identical antigen binding sites although IgM usually has relatively low affinity for its antigen. Its heavy chain is type mu (µ).

==Production==
Produced by plasma cells in the spleen, bone marrow and lymph nodes. Since it is around five times larger than "normal" antibody it does not diffuse quickly or enter tissues readily and as such its concentration in extracellular fluid and lymph is very low. It does not cross the placenta even in animals with haemochorial placentas e.g. apes. 
IgM is the first class of antibody produced by plasma cells, with production replaced by either [[IgG]] or [[IgE]] in a process known as '''[[Immunoglobulin overview|class-switching]]''' once the secondary immune response is initiated 

==Function==

IgM mainly functions as a target for [[Complement|complement]] activation as well as roles in agglutination, opsonisation and virus neutralisation.
 
----
<center>[[Immunoglobulins|Immunoglobulins]]: [[Immunoglobulin A|Immunoglobulin A]], [[Immunoglobulin D|Immunoglobulin D]], [[Immunoglobulin E|Immunoglobulin E]], [[Immunoglobulin G|Immunoglobulin G]] & [[Immunoglobulin M|Immunoglobulin M]]</center>

 
{{Jim Bee 2007}}
[[Category:Immunoglobulins]]
[[Category:A&P Done]]

Immunoglobulin M

2012-05-25T10:09:22Z

Rjfrancisrvc:

{{review}}
''Shortened to IgM''
[[Image:LH IgM.png|thumb|150px|right|'''IgM'''1 = IgM monomer2 = Heavy chains3 = Light chains4 =J chain5 = Disulfide bonds]]
[[Image:IgM.jpg|thumb|right|150px|IgM - B. Catchpole, RVC 2008]]
==Overview==
Is found in high concentrations in blood plasma (below [[IgG]] conc.) and is the major Ig produced, by [[B cell differentiation|plasma cells]], during the primary immune response

==Structure==
IgM is the primordial antibody and, although a monomer, is secreted as a pentamer (five monomers joined by disulphide bonds with two monomers joined by a J chain). This gives it ten identical antigen binding sites although IgM usually has relatively low affinity for its antigen. Its heavy chain is type mu (µ).

==Production==
Produced by plasma cells in the spleen, bone marrow and lymph nodes. Since it is around five times larger than "normal" antibody it does not diffuse quickly or enter tissues readily and as such its concentration in extracellular fluid and lymph is very low. It does not cross the placenta even in animals with haemochorial placentas e.g. apes. 
IgM is the first class of antibody produced by plasma cells, with production replaced by either [[IgG]] or [[IgE]] in a process known as '''[[Immunoglogulin Overview|class-switching]]''' once the secondary immune response is initiated 
==Function==

IgM mainly functions as a target for [[Complement|complement]] activation as well as roles in agglutination, opsonisation and virus neutralisation.
 
----
<center>[[Immunoglobulins|Immunoglobulins]]: [[Immunoglobulin A|Immunoglobulin A]], [[Immunoglobulin D|Immunoglobulin D]], [[Immunoglobulin E|Immunoglobulin E]], [[Immunoglobulin G|Immunoglobulin G]] & [[Immunoglobulin M|Immunoglobulin M]]</center>

 
{{Jim Bee 2007}}
[[Category:Immunoglobulins]]
[[Category:A&P Done]]

Immunoglobulin M

2012-05-25T10:02:48Z

Rjfrancisrvc: /* Structure */

{{review}}
''Shortened to IgM''
[[Image:LH IgM.png|thumb|150px|right|'''IgM'''1 = IgM monomer2 = Heavy chains3 = Light chains4 =J chain5 = Disulfide bonds]]
[[Image:IgM.jpg|thumb|right|150px|IgM - B. Catchpole, RVC 2008]]
Is found in high concentrations in blood plasma (below [[IgG]] conc.) and is the major Ig produced during primary immune response
==Structure==
IgM is the primordial antibody and, although a monomer, is secreted as a pentamer (five monomers joined by disulphide bonds with two monomers joined by a J chain). This gives it ten identical antigen binding sites although IgM usually has relatively low affinity for its antigen. Its heavy chain is type mu (µ).

==Production==
Produced by plasma cells in the spleen, bone marrow and lymph nodes. Since it is around five times larger than "normal" antibody it does not diffuse quickly or enter tissues readily and as such its concentration in extracellular fluid and lymph is very low.
It does not cross the placenta even in animals with haemochorial placentas e.g. apes. 
==Function==

IgM mainly functions as a target for [[Complement|complement]] activation as well as roles in agglutination, opsonisation and virus neutralisation.
 
----
<center>[[Immunoglobulins|Immunoglobulins]]: [[Immunoglobulin A|Immunoglobulin A]], [[Immunoglobulin D|Immunoglobulin D]], [[Immunoglobulin E|Immunoglobulin E]], [[Immunoglobulin G|Immunoglobulin G]] & [[Immunoglobulin M|Immunoglobulin M]]</center>

 
{{Jim Bee 2007}}
[[Category:Immunoglobulins]]
[[Category:A&P Done]]

Immunoglobulin G

2012-05-25T09:59:57Z

Rjfrancisrvc: /* Overview */

==Overview==
[[Image:LH IgG.png|thumb|250px|right|'''IgG''']]
[[Image:IgG.jpg|thumb|right|250px|IgG - B. Catchpole, RVC 2008]]

''Shortened to IgG''

IgG is the major antibody in blood plasma, and constitutes at least 80% of all antibodies in the body. It is the smallest immunoglobulin, so can readily leave the blood plasma and enter tissues. They can also cross the placenta, providing adaptive immunity to the foetus when the mother is under attack. IgG is also present in breast milk.

==Structure==

IgG is Y-shaped, with three constant regions and a heavy chain subunit type γ. There are several different IgG subclasses, depending on the species coded for by the IGHG gene.

'''Ruminants'''

Have three subclasses, G1-G3. IgG1 is the major antibody in ruminant mucosal secretions and colostrum.

'''Dogs, rodents and cats'''

Have four subclasses. Dogs: G1-G4; Rodents: G1, G2a, G2b, G3. Cats are unknown.

'''Pigs'''

Have five subclasses, G1-G4 (G2a, G2b).

'''Horses'''

Have six subclasses, G1-G6.

==Production==

IgG is produced by [[B cell differentiation|plasma cells]] in the spleen, bone marrow and lymph nodes.

==Function==

Some IgG subclasses can activate complement via the classical pathway. Some subclasses act as targets for [[Macrophages|macrophages]], [[Eosinophils|eosinophils]] and [[Neutrophils|neutrophils]]. It is therefore the major antibody in tissue fluids and lymph. IgG specifically binds to antigens on bacteria, causing agglutination and opsonisation.

==Links==

[[Immunoglobulins|Immunoglobulins]]

[[Immunoglobulin A|Immunoglobulin A]]

[[Immunoglobulin D|Immunoglobulin D]]

[[Immunoglobulin E|Immunoglobulin E]]

[[Immunoglobulin M|Immunoglobulin M]]

 
{{Jim Bee 2007}}
[[Category:Immunoglobulins]]
[[Category:A&P Done]]

Immunoglobulin G

2012-05-25T09:58:07Z

Rjfrancisrvc: /* Production */

==Overview==
[[Image:LH IgG.png|thumb|250px|right|'''IgG''']]
[[Image:IgG.jpg|thumb|right|250px|IgG - B. Catchpole, RVC 2008]]

''Shortened to IgG''

IgG is the major antibody in blood plasma, and constitutes at least 80% of all antibodies in the body. It is the smallest immunoglobulin, so can readily leave the blood plasma and enter tissues.

==Structure==

IgG is Y-shaped, with three constant regions and a heavy chain subunit type γ. There are several different IgG subclasses, depending on the species coded for by the IGHG gene.

'''Ruminants'''

Have three subclasses, G1-G3. IgG1 is the major antibody in ruminant mucosal secretions and colostrum.

'''Dogs, rodents and cats'''

Have four subclasses. Dogs: G1-G4; Rodents: G1, G2a, G2b, G3. Cats are unknown.

'''Pigs'''

Have five subclasses, G1-G4 (G2a, G2b).

'''Horses'''

Have six subclasses, G1-G6.

==Production==

IgG is produced by [[B cell differentiation|plasma cells]] in the spleen, bone marrow and lymph nodes.

==Function==

Some IgG subclasses can activate complement via the classical pathway. Some subclasses act as targets for [[Macrophages|macrophages]], [[Eosinophils|eosinophils]] and [[Neutrophils|neutrophils]]. It is therefore the major antibody in tissue fluids and lymph. IgG specifically binds to antigens on bacteria, causing agglutination and opsonisation.

==Links==

[[Immunoglobulins|Immunoglobulins]]

[[Immunoglobulin A|Immunoglobulin A]]

[[Immunoglobulin D|Immunoglobulin D]]

[[Immunoglobulin E|Immunoglobulin E]]

[[Immunoglobulin M|Immunoglobulin M]]

 
{{Jim Bee 2007}}
[[Category:Immunoglobulins]]
[[Category:A&P Done]]

Immunity to Parasites

2012-05-25T09:56:24Z

Rjfrancisrvc: /* Innate Immunity */

==Innate Immunity==
[[File:Helminth Killing edit.png|300px|right|thumb|Helminth Killing - R.J.Francis, RVC 2012]]
[[File:Helmith Killing by Granulocytes.png|250px|right|thumb|Electron Micrograph of Helminth Killing by Granulocytes (G). Adapted from [[http://eprints.adm.unipi.it/527/]] - R.J.Francis, RVC 2012]]
The first line of defence against parasitic infection are the effector mechanisms of the innate immune system. The '''[[Macrophages|macrophages]]''' are important players in the defence against extracellular parasites. This is because macrophages are able to secrete [[Cytokines|cytokines]] as well as perform [[Phagocytosis|phagocytosis]]. In this they can act as 'killer cells' through antibody-dependent cell-mediated cytotoxicity, for example specific [[Immunoglobulins|IgG]]/[[Immunoglobulins|IgE]] enhances the ability of macrophages to kill schistosomules through the interaction of Fc receptors on the surface of the macrophage. Of the secreted cytokines, the secretion of TNFα is of particular importance. This is because TNFα activates other macrophages and can have toxic effects in high amounts. TNFα also renders hepatocytes resistant to malarial infection when in conjunction with IL-1. Cytokine secretion (in particular IFNγ) can also enhance killing by mechanisms using free radicals and O2-independent toxins (e.g. nitric oxide).
 
 
As well as the macrophages, the granulocytes form the main effector response to parasitic infection. '''[[Eosinophils|Eosinophils]]''' are very important in the destruction of larger parasites even though they are less phagocytic than [[Neutrophils|neutrophils]]. Most activity from eosinophils is controlled by antigen-specific mechanisms, for example binding to worms coated with [[IgG]]/[[IgE]] increases '''degranulation'''. Degranulation, through the process known as '''exocytosis''', releases enzymes that degrade the parasite into smaller chunks so it can be cleared by phagocytosis. The eosinophils also form the end point of the adaptive immune response to larger parasites with the killing of some larvae being enhanced by the activity of mast cells, for example antigens released by ''S. mansoni'' cause IgE-dependent degranulation of mast cells, the products of which selectively attract eosinophils. Mast cells and eosinophils degranulation enhances the TH2 response through the release of [[Cytokines|cytokines]], for example IL-4 and IL-13, that is needed to clear a stubborn infection.
 
 
The other granulocytes present in parasite-infected inflammatory lesions and involved in the anti-parasitic response are the '''[[Neutrophils|neutrophils]]'''. In the parasitic response they have similar properties to macrophages with activation caused by cytokines such as TNFα, IFNγ and GM-CSF. Their mechanism for killing is by an intense respiratory burst, with extracellular killing being mediated by hydrogen peroxide (H2O2). In addition, they also express Fc and [[Complement|complement]] receptors so can participate in antibody-dependent cell-mediated cytotoxicity and [[Phagocytosis|phagocytosis]]. Due to innate inflammatory mechanisms neutrophils are early responders to parasite infection.
 
 
'''[[Platelets|Platelets]]''' also form part of the innate immune response to parasites. Their main mode of action is the binding and release of granular contents, in particular inflammatory peptides. The cytotoxic activity of plateltes is increased by cytokines such as TNFα and IFNγ. The potential targets include the larval stage of flukes, e.g. ''T. gondii'', ''T. cruzi'' and ''S. Mansoni''. Like other effector cells, platelets express Fc receptors, making them able to perform antibody-dependent cytotoxicity.

==Adaptive Immunity==
Although the innate immune system provides an effective first line of defence, '''[[T cells|T cells]]''' are fundamental in the development of immunity, demonstrated using T-cell deprived mice that fail to resolve otherwise non-lethal infections of, for example, ''T. cruzi''.
*Both CD4+ and CD8+ cells are required for protection, e.g CD4+ cells protect against the blood stage of a Plasmodium infection (erythrocytes do not express MHC class I), while CD8+ cells are required to mediate immunity against the liver stage (hepatocytes do not express MHC class II).
*TH1 cells are required to fight intracellular protozoa - the release of IFNγ activates macrophages to kill the protozoa residing within them
*Helminth infections require both TH1 and TH2 responses, e.g. during ''S. mansoni'' the secretion of IFNγ by TH1 cells activates mechanisms that destroy larvae in the lungs, although the TH2 subset, secreting IL-5, predominate. IL-5 is responsible for the eosinophilia associated with parasite infections.
*TH2 cells are required for the destruction of intestinal worms, where they induce mucosal mast cells and interact with [[Eosinophils|eosinophils]]
While cell-mediated immunity is important in tissue infections, such as Leishmania, specific antibodies are important in controlling parasites that live in the bloodstream, e.g. malaria. Mechanisms of antibody-mediated immunity include:
*Directly damaging protozoa
*Activating [[Complement|complement]], and the subsequent Membrane Attack Complex
*Blocking attachment to host cells
*Enhancing macrophage phagocytosis
*Involvement in antibody-dependent cell-mediated cytotoxicity

=='''Immunopathology'''==
The immunopathology is the damage resulting from an immune response to the parasites. Examples include:
*The increase in macrophages and lymphocytes in the liver and spleen can lead to swelling of these organs, e.g. visceral leishmaniasis
*T-cell dependent (TH1 and TH17) granulomas forming in organs, e.g. schistosomiasis in the liver
*The pathology of elephantiasis is thought to be due to changes in the adult filariae in the lymphatic system
*Formation of immune complexes, e.g. deposition in the kidney during malarial infection
*Anaphylactic shock caused by [[IgE]] production, e.g. after the rupture of hydatid cysts
*Cross-reaction of antibodies with host tissue, e.g. ''O. volvulus'', the cause of river blindness, expresses an antigen similar to a protein in the retina
*Excessive production of cytokines, such as TNFα, may contribute to pathology of diseases such as malaria

=='''Evading immune defences'''==

Parasites can evade an immune response from the host by changing the antigens presented to the host, produce antigens that mimic the host's antigens and can produce down-regulating factors which suppress or modify the host's immune responses. Having a rapid turnover of their surface coat when host cells bind and by being able to live in sites which are protected from the host's immune response allow parasites to establish themselves in a particular species.
*Selection of innapropriate defences - by exploiting the 'adjuvant' mechanism, some parasites are able to activate the inappropriate helper T cell subset, e.g Leishmania
*Antigenic variation avoids recognition by antibody and complement, e.g. ''T. brucei''
*Inhibiting fusion of lysosomes
*Escaping into the cytoplasm, e.g. ''T. cruzi''
*Inhibiting respiratory burst, e.g. Leishmania
*Forming cysts in muscle tissue, e.g. ''T. spiralis'' - also develops decay accelerating factor (DAF)
*Production of antioxidants, e.g. ''W. bancrofti''

<big>'''Also see [[Adaptive Immunity to Parasites]]'''</big>

[[Category:Parasites]]

[[Category:To_Do_-_Blood]]

Immunity to Parasites

2012-05-25T09:52:43Z

Rjfrancisrvc: /* Innate Immunity */

==Innate Immunity==
[[File:Helminth Killing.png|300px|right|thumb|Helminth Killing - R.J.Francis, RVC 2012]]
[[File:Helmith Killing by Granulocytes.png|250px|right|thumb|Electron Micrograph of Helminth Killing by Granulocytes (G). Adapted from [[http://eprints.adm.unipi.it/527/]] - R.J.Francis, RVC 2012]]
The first line of defence against parasitic infection are the effector mechanisms of the innate immune system. The '''[[Macrophages|macrophages]]''' are important players in the defence against extracellular parasites. This is because macrophages are able to secrete [[Cytokines|cytokines]] as well as perform [[Phagocytosis|phagocytosis]]. In this they can act as 'killer cells' through antibody-dependent cell-mediated cytotoxicity, for example specific [[Immunoglobulins|IgG]]/[[Immunoglobulins|IgE]] enhances the ability of macrophages to kill schistosomules through the interaction of Fc receptors on the surface of the macrophage. Of the secreted cytokines, the secretion of TNFα is of particular importance. This is because TNFα activates other macrophages and can have toxic effects in high amounts. TNFα also renders hepatocytes resistant to malarial infection when in conjunction with IL-1. Cytokine secretion (in particular IFNγ) can also enhance killing by mechanisms using free radicals and O2-independent toxins (e.g. nitric oxide).
 
 
As well as the macrophages, the granulocytes form the main effector response to parasitic infection. '''[[Eosinophils|Eosinophils]]''' are very important in the destruction of larger parasites even though they are less phagocytic than [[Neutrophils|neutrophils]]. Most activity from eosinophils is controlled by antigen-specific mechanisms, for example binding to worms coated with [[IgG]]/[[IgE]] increases '''degranulation'''. Degranulation, through the process known as '''exocytosis''', releases enzymes that degrade the parasite into smaller chunks so it can be cleared by phagocytosis. The eosinophils also form the end point of the adaptive immune response to larger parasites with the killing of some larvae being enhanced by the activity of mast cells, for example antigens released by ''S. mansoni'' cause IgE-dependent degranulation of mast cells, the products of which selectively attract eosinophils. Mast cells and eosinophils degranulation enhances the TH2 response through the release of [[Cytokines|cytokines]], for example IL-4 and IL-13, that is needed to clear a stubborn infection.
 
 
The other granulocytes present in parasite-infected inflammatory lesions and involved in the anti-parasitic response are the '''[[Neutrophils|neutrophils]]'''. In the parasitic response they have similar properties to macrophages with activation caused by cytokines such as TNFα, IFNγ and GM-CSF. Their mechanism for killing is by an intense respiratory burst, with extracellular killing being mediated by hydrogen peroxide (H2O2). In addition, they also express Fc and [[Complement|complement]] receptors so can participate in antibody-dependent cell-mediated cytotoxicity and [[Phagocytosis|phagocytosis]]. Due to innate inflammatory mechanisms neutrophils are early responders to parasite infection.
 
 
'''[[Platelets|Platelets]]''' also form part of the innate immune response to parasites. Their main mode of action is the binding and release of granular contents, in particular inflammatory peptides. The cytotoxic activity of plateltes is increased by cytokines such as TNFα and IFNγ. The potential targets include the larval stage of flukes, e.g. ''T. gondii'', ''T. cruzi'' and ''S. Mansoni''. Like other effector cells, platelets express Fc receptors, making them able to perform antibody-dependent cytotoxicity.

==Adaptive Immunity==
Although the innate immune system provides an effective first line of defence, '''[[T cells|T cells]]''' are fundamental in the development of immunity, demonstrated using T-cell deprived mice that fail to resolve otherwise non-lethal infections of, for example, ''T. cruzi''.
*Both CD4+ and CD8+ cells are required for protection, e.g CD4+ cells protect against the blood stage of a Plasmodium infection (erythrocytes do not express MHC class I), while CD8+ cells are required to mediate immunity against the liver stage (hepatocytes do not express MHC class II).
*TH1 cells are required to fight intracellular protozoa - the release of IFNγ activates macrophages to kill the protozoa residing within them
*Helminth infections require both TH1 and TH2 responses, e.g. during ''S. mansoni'' the secretion of IFNγ by TH1 cells activates mechanisms that destroy larvae in the lungs, although the TH2 subset, secreting IL-5, predominate. IL-5 is responsible for the eosinophilia associated with parasite infections.
*TH2 cells are required for the destruction of intestinal worms, where they induce mucosal mast cells and interact with [[Eosinophils|eosinophils]]
While cell-mediated immunity is important in tissue infections, such as Leishmania, specific antibodies are important in controlling parasites that live in the bloodstream, e.g. malaria. Mechanisms of antibody-mediated immunity include:
*Directly damaging protozoa
*Activating [[Complement|complement]], and the subsequent Membrane Attack Complex
*Blocking attachment to host cells
*Enhancing macrophage phagocytosis
*Involvement in antibody-dependent cell-mediated cytotoxicity

=='''Immunopathology'''==
The immunopathology is the damage resulting from an immune response to the parasites. Examples include:
*The increase in macrophages and lymphocytes in the liver and spleen can lead to swelling of these organs, e.g. visceral leishmaniasis
*T-cell dependent (TH1 and TH17) granulomas forming in organs, e.g. schistosomiasis in the liver
*The pathology of elephantiasis is thought to be due to changes in the adult filariae in the lymphatic system
*Formation of immune complexes, e.g. deposition in the kidney during malarial infection
*Anaphylactic shock caused by [[IgE]] production, e.g. after the rupture of hydatid cysts
*Cross-reaction of antibodies with host tissue, e.g. ''O. volvulus'', the cause of river blindness, expresses an antigen similar to a protein in the retina
*Excessive production of cytokines, such as TNFα, may contribute to pathology of diseases such as malaria

=='''Evading immune defences'''==

Parasites can evade an immune response from the host by changing the antigens presented to the host, produce antigens that mimic the host's antigens and can produce down-regulating factors which suppress or modify the host's immune responses. Having a rapid turnover of their surface coat when host cells bind and by being able to live in sites which are protected from the host's immune response allow parasites to establish themselves in a particular species.
*Selection of innapropriate defences - by exploiting the 'adjuvant' mechanism, some parasites are able to activate the inappropriate helper T cell subset, e.g Leishmania
*Antigenic variation avoids recognition by antibody and complement, e.g. ''T. brucei''
*Inhibiting fusion of lysosomes
*Escaping into the cytoplasm, e.g. ''T. cruzi''
*Inhibiting respiratory burst, e.g. Leishmania
*Forming cysts in muscle tissue, e.g. ''T. spiralis'' - also develops decay accelerating factor (DAF)
*Production of antioxidants, e.g. ''W. bancrofti''

<big>'''Also see [[Adaptive Immunity to Parasites]]'''</big>

[[Category:Parasites]]

[[Category:To_Do_-_Blood]]

Immunoglobulin E

2012-05-25T09:45:41Z

Rjfrancisrvc: /* Function */

==Overview==
[[Image:LH IgE.png|thumb|250px|right|'''IgE''']]
[[Image:IgE.jpg|thumb|right|250px|IgE - B. Catchpole, RVC 2008]]

Commonly referred to as ''IgE''.

Unlike [[IgM]], [[IgG]] and [[IgA]], IgE does not function as a soluble antibody, with binding to Fcε receptors before it can bind to the target, and is found in low levels in blood plasma. Like [[IgA]], it is produced by [[B cell differentiation|plasma cells]] and is mainly localised to mucosal surfaces.

==Structure==

IgE is Y-shaped with heavy chain type ε, and exists as a monomer.

''Note: Janeway <ref>{{citation|initiallast = Janeway|initialfirst = C.A|2last = Travers|2first = P|3last = Walport|3first = M|finallast = Shlomchik|finalfirst = M.J|year = 2005|title = Immunobiology: The immune system in health and disease|ed = 6th |city = New York|pub = Garland Science Publishing|range = 156-157}}</ref> states that IgE has no hinge region whereas Tizard <ref>{{citation|initiallast = Tizard|initialfirst = I.R|year = 2004|title = Veterinary Immunology: An Introduction|ed = 7th|city = Philadelphia|pub = Saunders|range = 148-149}}</ref> indicates that it does.''

==Production==

It is produced when TH2 cells stimulate CD40 and produce IL-4 and IL-13, which causes B cell differentiation to plasma cells and class switching to IgE production.

==Function==

IgE triggers acute inflammation by binding to the FCεRI receptors on mast cells in the lamina propria and [[Basophils|basophils]], causing degranulation when bound to target. It is involved in [[Type I Hypersensitivity|type I hypersensitivity reactions]]. Cross-linking of IgE molecules by antigens, triggers [[Mast Cells|mast cell]] and [[Eosinophil|eosinophil]] degranulation and an inflammatory response. IgE has considerable involvement in producing [[Immunity to Parasites|immunity to parasitic worms]], particularly [[:Category:Nematodes|nematode]] parasites. It may mediate their expulsion or killing via mast cell activity, cytotoxic [[Eosinophils|eosinophils]], [[Macrophages|macrophages]], and so on.

==References==
<references />
 

==Links==

[[Immunoglobulins|Immunoglobulins]]

[[Immunoglobulin A|Immunoglobulin A]]

[[Immunoglobulin D|Immunoglobulin D]]

[[Immunoglobulin G|Immunoglobulin G]]

[[Immunoglobulin M|Immunoglobulin M]]
 
{{Jim Bee 2007}}
[[Category:Immunoglobulins]]
[[Category:A&P Done]]

Immunoglobulin E

2012-05-25T09:45:29Z

Rjfrancisrvc: /* Function */

==Overview==
[[Image:LH IgE.png|thumb|250px|right|'''IgE''']]
[[Image:IgE.jpg|thumb|right|250px|IgE - B. Catchpole, RVC 2008]]

Commonly referred to as ''IgE''.

Unlike [[IgM]], [[IgG]] and [[IgA]], IgE does not function as a soluble antibody, with binding to Fcε receptors before it can bind to the target, and is found in low levels in blood plasma. Like [[IgA]], it is produced by [[B cell differentiation|plasma cells]] and is mainly localised to mucosal surfaces.

==Structure==

IgE is Y-shaped with heavy chain type ε, and exists as a monomer.

''Note: Janeway <ref>{{citation|initiallast = Janeway|initialfirst = C.A|2last = Travers|2first = P|3last = Walport|3first = M|finallast = Shlomchik|finalfirst = M.J|year = 2005|title = Immunobiology: The immune system in health and disease|ed = 6th |city = New York|pub = Garland Science Publishing|range = 156-157}}</ref> states that IgE has no hinge region whereas Tizard <ref>{{citation|initiallast = Tizard|initialfirst = I.R|year = 2004|title = Veterinary Immunology: An Introduction|ed = 7th|city = Philadelphia|pub = Saunders|range = 148-149}}</ref> indicates that it does.''

==Production==

It is produced when TH2 cells stimulate CD40 and produce IL-4 and IL-13, which causes B cell differentiation to plasma cells and class switching to IgE production.

==Function==

IgE triggers acute inflammation by binding to the FCεRI receptors on mast cells in the lamina propria and [[Basophils|basophils]], causing degranulation when bound to target. It is involved in [[Type I Hypersensitivity|type I hypersensitivity reactions]]. Cross-linking of IgE molecules by antigens, triggers [[Mast Cells|mast cell]] and Eosinophil|eosinophil]] degranulation and an inflammatory response. IgE has considerable involvement in producing [[Immunity to Parasites|immunity to parasitic worms]], particularly [[:Category:Nematodes|nematode]] parasites. It may mediate their expulsion or killing via mast cell activity, cytotoxic [[Eosinophils|eosinophils]], [[Macrophages|macrophages]], and so on.

==References==
<references />
 

==Links==

[[Immunoglobulins|Immunoglobulins]]

[[Immunoglobulin A|Immunoglobulin A]]

[[Immunoglobulin D|Immunoglobulin D]]

[[Immunoglobulin G|Immunoglobulin G]]

[[Immunoglobulin M|Immunoglobulin M]]
 
{{Jim Bee 2007}}
[[Category:Immunoglobulins]]
[[Category:A&P Done]]

Immunoglobulin E

2012-05-25T09:44:15Z

Rjfrancisrvc: /* Function */

==Overview==
[[Image:LH IgE.png|thumb|250px|right|'''IgE''']]
[[Image:IgE.jpg|thumb|right|250px|IgE - B. Catchpole, RVC 2008]]

Commonly referred to as ''IgE''.

Unlike [[IgM]], [[IgG]] and [[IgA]], IgE does not function as a soluble antibody, with binding to Fcε receptors before it can bind to the target, and is found in low levels in blood plasma. Like [[IgA]], it is produced by [[B cell differentiation|plasma cells]] and is mainly localised to mucosal surfaces.

==Structure==

IgE is Y-shaped with heavy chain type ε, and exists as a monomer.

''Note: Janeway <ref>{{citation|initiallast = Janeway|initialfirst = C.A|2last = Travers|2first = P|3last = Walport|3first = M|finallast = Shlomchik|finalfirst = M.J|year = 2005|title = Immunobiology: The immune system in health and disease|ed = 6th |city = New York|pub = Garland Science Publishing|range = 156-157}}</ref> states that IgE has no hinge region whereas Tizard <ref>{{citation|initiallast = Tizard|initialfirst = I.R|year = 2004|title = Veterinary Immunology: An Introduction|ed = 7th|city = Philadelphia|pub = Saunders|range = 148-149}}</ref> indicates that it does.''

==Production==

It is produced when TH2 cells stimulate CD40 and produce IL-4 and IL-13, which causes B cell differentiation to plasma cells and class switching to IgE production.

==Function==

IgE triggers acute inflammation by binding to the FCεRI receptors on mast cells in the lamina propria and [[Basophils|basophils]], causing degranulation. It is involved in [[Type I Hypersensitivity|type I hypersensitivity reactions]]. Cross-linking of IgE molecules by antigens, triggers [[Mast Cells|mast cell]] degranulation and an inflammatory response. IgE has considerable involvement in producing [[Immunity to Parasites|immunity to parasitic worms]], particularly [[:Category:Nematodes|nematode]] parasites. It may mediate their expulsion or killing via mast cell activity, cytotoxic [[Eosinophils|eosinophils]], [[Macrophages|macrophages]], and so on.

==References==
<references />
 

==Links==

[[Immunoglobulins|Immunoglobulins]]

[[Immunoglobulin A|Immunoglobulin A]]

[[Immunoglobulin D|Immunoglobulin D]]

[[Immunoglobulin G|Immunoglobulin G]]

[[Immunoglobulin M|Immunoglobulin M]]
 
{{Jim Bee 2007}}
[[Category:Immunoglobulins]]
[[Category:A&P Done]]

Immunoglobulin E

2012-05-25T09:41:51Z

Rjfrancisrvc: /* Overview */

==Overview==
[[Image:LH IgE.png|thumb|250px|right|'''IgE''']]
[[Image:IgE.jpg|thumb|right|250px|IgE - B. Catchpole, RVC 2008]]

Commonly referred to as ''IgE''.

Unlike [[IgM]], [[IgG]] and [[IgA]], IgE does not function as a soluble antibody, with binding to Fcε receptors before it can bind to the target, and is found in low levels in blood plasma. Like [[IgA]], it is produced by [[B cell differentiation|plasma cells]] and is mainly localised to mucosal surfaces.

==Structure==

IgE is Y-shaped with heavy chain type ε, and exists as a monomer.

''Note: Janeway <ref>{{citation|initiallast = Janeway|initialfirst = C.A|2last = Travers|2first = P|3last = Walport|3first = M|finallast = Shlomchik|finalfirst = M.J|year = 2005|title = Immunobiology: The immune system in health and disease|ed = 6th |city = New York|pub = Garland Science Publishing|range = 156-157}}</ref> states that IgE has no hinge region whereas Tizard <ref>{{citation|initiallast = Tizard|initialfirst = I.R|year = 2004|title = Veterinary Immunology: An Introduction|ed = 7th|city = Philadelphia|pub = Saunders|range = 148-149}}</ref> indicates that it does.''

==Production==

It is produced when TH2 cells stimulate CD40 and produce IL-4 and IL-13, which causes B cell differentiation to plasma cells and class switching to IgE production.

==Function==

IgE triggers acute inflammation by binding to the FCεRI receptors on mast cells in the lamina propria and [[Basophils|basophils]], causing degranulation. It is involved in [[Type I Hypersensitivity|type I hypersensitivity reactions]]. Cross-linking of IgE molecules by antigens, triggers [[Mast Cells|mast cell]] degranulation and an inflammatory response. IgE has considerable involvement in producing immunity to parasitic worms, particularly [[:Category:Nematodes|nematode]] parasites. It may mediate their expulsion or killing via mast cell activity, cytotoxic [[Eosinophils|eosinophils]], [[Macrophages|macrophages]], and so on.

==References==
<references />
 

==Links==

[[Immunoglobulins|Immunoglobulins]]

[[Immunoglobulin A|Immunoglobulin A]]

[[Immunoglobulin D|Immunoglobulin D]]

[[Immunoglobulin G|Immunoglobulin G]]

[[Immunoglobulin M|Immunoglobulin M]]
 
{{Jim Bee 2007}}
[[Category:Immunoglobulins]]
[[Category:A&P Done]]

Immunoglobulin E

2012-05-25T09:41:00Z

Rjfrancisrvc: /* Overview */

==Overview==
[[Image:LH IgE.png|thumb|250px|right|'''IgE''']]
[[Image:IgE.jpg|thumb|right|250px|IgE - B. Catchpole, RVC 2008]]

Commonly referred to as ''IgE''.

Unlike [[IgM]], [[IgG]] and [[IgA]], IgE does not function as a soluble antibody, with binding to Fcε receptors before it can bind to the target, and is found in low levels in blood plasma. Like [[IgA]], it is produced by [[B Cell Differentiation|plasma cells]] and is mainly localised to mucosal surfaces.

==Structure==

IgE is Y-shaped with heavy chain type ε, and exists as a monomer.

''Note: Janeway <ref>{{citation|initiallast = Janeway|initialfirst = C.A|2last = Travers|2first = P|3last = Walport|3first = M|finallast = Shlomchik|finalfirst = M.J|year = 2005|title = Immunobiology: The immune system in health and disease|ed = 6th |city = New York|pub = Garland Science Publishing|range = 156-157}}</ref> states that IgE has no hinge region whereas Tizard <ref>{{citation|initiallast = Tizard|initialfirst = I.R|year = 2004|title = Veterinary Immunology: An Introduction|ed = 7th|city = Philadelphia|pub = Saunders|range = 148-149}}</ref> indicates that it does.''

==Production==

It is produced when TH2 cells stimulate CD40 and produce IL-4 and IL-13, which causes B cell differentiation to plasma cells and class switching to IgE production.

==Function==

IgE triggers acute inflammation by binding to the FCεRI receptors on mast cells in the lamina propria and [[Basophils|basophils]], causing degranulation. It is involved in [[Type I Hypersensitivity|type I hypersensitivity reactions]]. Cross-linking of IgE molecules by antigens, triggers [[Mast Cells|mast cell]] degranulation and an inflammatory response. IgE has considerable involvement in producing immunity to parasitic worms, particularly [[:Category:Nematodes|nematode]] parasites. It may mediate their expulsion or killing via mast cell activity, cytotoxic [[Eosinophils|eosinophils]], [[Macrophages|macrophages]], and so on.

==References==
<references />
 

==Links==

[[Immunoglobulins|Immunoglobulins]]

[[Immunoglobulin A|Immunoglobulin A]]

[[Immunoglobulin D|Immunoglobulin D]]

[[Immunoglobulin G|Immunoglobulin G]]

[[Immunoglobulin M|Immunoglobulin M]]
 
{{Jim Bee 2007}}
[[Category:Immunoglobulins]]
[[Category:A&P Done]]

Immunoglobulin E

2012-05-25T09:40:49Z

Rjfrancisrvc: /* Overview */

==Overview==
[[Image:LH IgE.png|thumb|250px|right|'''IgE''']]
[[Image:IgE.jpg|thumb|right|250px|IgE - B. Catchpole, RVC 2008]]

Commonly referred to as ''IgE''.

Unlike [[IgM]], [[IgG]] and [[IgA]], IgE does not function as a soluble antibody, with binding to Fcε receptors before it can bind to the target, and is found in low levels in blood plasma. Like [[IgA]], it is produced by [[B cell Differentiation|plasma cells]] and is mainly localised to mucosal surfaces.

==Structure==

IgE is Y-shaped with heavy chain type ε, and exists as a monomer.

''Note: Janeway <ref>{{citation|initiallast = Janeway|initialfirst = C.A|2last = Travers|2first = P|3last = Walport|3first = M|finallast = Shlomchik|finalfirst = M.J|year = 2005|title = Immunobiology: The immune system in health and disease|ed = 6th |city = New York|pub = Garland Science Publishing|range = 156-157}}</ref> states that IgE has no hinge region whereas Tizard <ref>{{citation|initiallast = Tizard|initialfirst = I.R|year = 2004|title = Veterinary Immunology: An Introduction|ed = 7th|city = Philadelphia|pub = Saunders|range = 148-149}}</ref> indicates that it does.''

==Production==

It is produced when TH2 cells stimulate CD40 and produce IL-4 and IL-13, which causes B cell differentiation to plasma cells and class switching to IgE production.

==Function==

IgE triggers acute inflammation by binding to the FCεRI receptors on mast cells in the lamina propria and [[Basophils|basophils]], causing degranulation. It is involved in [[Type I Hypersensitivity|type I hypersensitivity reactions]]. Cross-linking of IgE molecules by antigens, triggers [[Mast Cells|mast cell]] degranulation and an inflammatory response. IgE has considerable involvement in producing immunity to parasitic worms, particularly [[:Category:Nematodes|nematode]] parasites. It may mediate their expulsion or killing via mast cell activity, cytotoxic [[Eosinophils|eosinophils]], [[Macrophages|macrophages]], and so on.

==References==
<references />
 

==Links==

[[Immunoglobulins|Immunoglobulins]]

[[Immunoglobulin A|Immunoglobulin A]]

[[Immunoglobulin D|Immunoglobulin D]]

[[Immunoglobulin G|Immunoglobulin G]]

[[Immunoglobulin M|Immunoglobulin M]]
 
{{Jim Bee 2007}}
[[Category:Immunoglobulins]]
[[Category:A&P Done]]

Immunoglobulin E

2012-05-25T09:40:14Z

Rjfrancisrvc: /* Overview */

==Overview==
[[Image:LH IgE.png|thumb|250px|right|'''IgE''']]
[[Image:IgE.jpg|thumb|right|250px|IgE - B. Catchpole, RVC 2008]]

Commonly referred to as ''IgE''.

Unlike [[IgM]], [[IgG]] and [[IgA]], IgE does not function as a soluble antibody, with binding to Fcε receptors before it can bind to the target, and is found in low levels in blood plasma. Like [[IgA]], it is produced by plasma cells and is mainly localised to mucosal surfaces.

==Structure==

IgE is Y-shaped with heavy chain type ε, and exists as a monomer.

''Note: Janeway <ref>{{citation|initiallast = Janeway|initialfirst = C.A|2last = Travers|2first = P|3last = Walport|3first = M|finallast = Shlomchik|finalfirst = M.J|year = 2005|title = Immunobiology: The immune system in health and disease|ed = 6th |city = New York|pub = Garland Science Publishing|range = 156-157}}</ref> states that IgE has no hinge region whereas Tizard <ref>{{citation|initiallast = Tizard|initialfirst = I.R|year = 2004|title = Veterinary Immunology: An Introduction|ed = 7th|city = Philadelphia|pub = Saunders|range = 148-149}}</ref> indicates that it does.''

==Production==

It is produced when TH2 cells stimulate CD40 and produce IL-4 and IL-13, which causes B cell differentiation to plasma cells and class switching to IgE production.

==Function==

IgE triggers acute inflammation by binding to the FCεRI receptors on mast cells in the lamina propria and [[Basophils|basophils]], causing degranulation. It is involved in [[Type I Hypersensitivity|type I hypersensitivity reactions]]. Cross-linking of IgE molecules by antigens, triggers [[Mast Cells|mast cell]] degranulation and an inflammatory response. IgE has considerable involvement in producing immunity to parasitic worms, particularly [[:Category:Nematodes|nematode]] parasites. It may mediate their expulsion or killing via mast cell activity, cytotoxic [[Eosinophils|eosinophils]], [[Macrophages|macrophages]], and so on.

==References==
<references />
 

==Links==

[[Immunoglobulins|Immunoglobulins]]

[[Immunoglobulin A|Immunoglobulin A]]

[[Immunoglobulin D|Immunoglobulin D]]

[[Immunoglobulin G|Immunoglobulin G]]

[[Immunoglobulin M|Immunoglobulin M]]
 
{{Jim Bee 2007}}
[[Category:Immunoglobulins]]
[[Category:A&P Done]]

Immunoglobulin E

2012-05-25T09:39:37Z

Rjfrancisrvc: /* Overview */

==Overview==
[[Image:LH IgE.png|thumb|250px|right|'''IgE''']]
[[Image:IgE.jpg|thumb|right|250px|IgE - B. Catchpole, RVC 2008]]

Commonly referred to as ''IgE''.

Unlike [[IgM]], [[IgG]] and [[IgA]], IgE does not function as a soluble antibody, with binding to Fcε receptors before it can bind to it's target, and is found in low levels in blood plasma. Like [[IgA]], it is produced by plasma cells and is mainly localised to mucosal surfaces.

==Structure==

IgE is Y-shaped with heavy chain type ε, and exists as a monomer.

''Note: Janeway <ref>{{citation|initiallast = Janeway|initialfirst = C.A|2last = Travers|2first = P|3last = Walport|3first = M|finallast = Shlomchik|finalfirst = M.J|year = 2005|title = Immunobiology: The immune system in health and disease|ed = 6th |city = New York|pub = Garland Science Publishing|range = 156-157}}</ref> states that IgE has no hinge region whereas Tizard <ref>{{citation|initiallast = Tizard|initialfirst = I.R|year = 2004|title = Veterinary Immunology: An Introduction|ed = 7th|city = Philadelphia|pub = Saunders|range = 148-149}}</ref> indicates that it does.''

==Production==

It is produced when TH2 cells stimulate CD40 and produce IL-4 and IL-13, which causes B cell differentiation to plasma cells and class switching to IgE production.

==Function==

IgE triggers acute inflammation by binding to the FCεRI receptors on mast cells in the lamina propria and [[Basophils|basophils]], causing degranulation. It is involved in [[Type I Hypersensitivity|type I hypersensitivity reactions]]. Cross-linking of IgE molecules by antigens, triggers [[Mast Cells|mast cell]] degranulation and an inflammatory response. IgE has considerable involvement in producing immunity to parasitic worms, particularly [[:Category:Nematodes|nematode]] parasites. It may mediate their expulsion or killing via mast cell activity, cytotoxic [[Eosinophils|eosinophils]], [[Macrophages|macrophages]], and so on.

==References==
<references />
 

==Links==

[[Immunoglobulins|Immunoglobulins]]

[[Immunoglobulin A|Immunoglobulin A]]

[[Immunoglobulin D|Immunoglobulin D]]

[[Immunoglobulin G|Immunoglobulin G]]

[[Immunoglobulin M|Immunoglobulin M]]
 
{{Jim Bee 2007}}
[[Category:Immunoglobulins]]
[[Category:A&P Done]]

Immunoglobulin D

2012-05-25T09:21:22Z

Rjfrancisrvc: /* Function */

[[Image:LH IgD.png|thumb|250px|right|'''IgD''']]
[[Image:IgD.jpg|thumb|right|250px|IgD - B. Catchpole, RVC 2008]]
==Overview==

''Shortened to IgD''.

IgD is present in ruminants, pigs, dogs and rodents but has not been identified in horses, cats, rabbits and chickens. It is mainly expressed on the surface of B-cells i.e. it is never secreted.

==Structure==

IgD is Y-shaped. In rodents, it has two δ heavy chain constant regions, whereas other mammals have three. IgD has a long hinge region and no disulfide bonds.

==Function==

IgD is only expressed in association with [[IgM]]. It is thought to be important in B-cell development, although it has been shown in δ chain knockout mice (so they have no functional IgD) do not have any noticeable defects in immune function.
 Interestingly IgD serum levels increase in allergic reactions, although it is not known why this is.

==Links==

[[Immunoglobulins|Immunoglobulins]]

[[Immunoglobulin A|Immunoglobulin A]]

[[Immunoglobulin E|Immunoglobulin E]]

[[Immunoglobulin G|Immunoglobulin G]]

[[Immunoglobulin M|Immunoglobulin M]]
 
{{Jim Bee 2007}}
[[Category:Immunoglobulins]]
[[Category:A&P Done]]

Immunoglobulin D

2012-05-25T09:16:55Z

Rjfrancisrvc:

[[Image:LH IgD.png|thumb|250px|right|'''IgD''']]
[[Image:IgD.jpg|thumb|right|250px|IgD - B. Catchpole, RVC 2008]]
==Overview==

''Shortened to IgD''.

IgD is present in ruminants, pigs, dogs and rodents but has not been identified in horses, cats, rabbits and chickens. It is mainly expressed on the surface of B-cells i.e. it is never secreted.

==Structure==

IgD is Y-shaped. In rodents, it has two δ heavy chain constant regions, whereas other mammals have three. IgD has a long hinge region and no disulfide bonds.

==Function==

IgD is only expressed in association with [[IgM]]. It is thought to be important in B-cell development, although it has been shown in δ chain knockout mice (so they have no functional IgD) do not have any noticeable defects in immune function.

==Links==

[[Immunoglobulins|Immunoglobulins]]

[[Immunoglobulin A|Immunoglobulin A]]

[[Immunoglobulin E|Immunoglobulin E]]

[[Immunoglobulin G|Immunoglobulin G]]

[[Immunoglobulin M|Immunoglobulin M]]
 
{{Jim Bee 2007}}
[[Category:Immunoglobulins]]
[[Category:A&P Done]]