Changes

[[Image:TH1-2.jpg|thumb|right|200px|TH1 and 2 selection is influenced by infection - B. Catchpole, RVC 2008]]

[[Image:TH1-2.jpg|thumb|right|200px|TH1 and 2 selection is influenced by infection - B. Catchpole, RVC 2008]]

==Introduction==

==Introduction==

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.  

[[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]].  

 

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 T_H0 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 cells, form in the presence of IL-6 and TGF-β which are produced in the prescence of infection.

 

The T_H0 cells have the capacity to differentiate into T_H1, T_H2 cells and a very recently described subtype T_H17 cells. The type of cell that develops depends on the antigen presenting cell type. [[Macrophages|Macrophages]] cause the T_H0 cell to develop into a T_H1 cell induced by IL-12 production following macrophage-antigen interaction. B cells cause the T_H0 cell to develop into a T_H2 cell induced by IL-10 production following B cell-antigen interaction. On antigenic stimulation the T_H1 or T_H2 cells become activated, undergo clonal expansion and secrete a range of different cytokines. The third most recently described subset, T_H17, 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⁺ T_H 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.

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.

**Helminths (SEA, ES 62)

**Helminths (SEA, ES 62)

*Endogenous

*Endogenous

**Inflammatory mediators (IL-1/TNF-a, hsp, FcR)  

**Inflammatory mediators (IL-1/TNFα, hsp, FcR)  

**Immune cells (CD40L, CD47, FasL)

**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]]

[[Image:Maturation of Dendritic Cells.jpg|thumb|right|300px|Maturation of Dendritic Cells - Copyright Prof Dirk Werling DrMedVet PhD MRCVS]]

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'''.

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==

==T_H1 Cells==

[[Image:TH1-macrophage.jpg|thumb|right|200px|TH-1 cells boost macrophage response - B. Catchpole, RVC 2008]]

[[Image:TH1-macrophage.jpg|thumb|right|200px|T_H1 cells boost macrophage response - B. Catchpole, RVC 2008]]

TH₁ cells help macrophages digest bacteria - the organisms are contained in cellular vesicles.

TH₁ cells help macrophages digest bacteria - the organisms are contained in cellular vesicles.

TH₁ cells secrete a range of cytokines, including:

T_H1 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.

* '''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 T_H1 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:

* '''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".

#Superoxide dismutase and myeloperoxidase that produce H₂O₂ and trigger the "superoxide burst".

#Nitric oxide synthase which produces nitric oxide.  

#Nitric oxide synthase which produces nitric oxide.  

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

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==

==T_H2 Cells==

[[Image:TH2-Bcell.jpg|thumb|right|200px|TH2 cells incite increased antibody production - B. Catchpole, RVC 2008]]

[[Image:TH2-Bcell.jpg|thumb|right|200px|T_H2 cells incite increased antibody production - B. Catchpole, RVC 2008]]

TH₂ cells help [[B cells]] produce antibody where the organism in present in tissue fluid. The TH₂ population influences B cell activation, proliferation and immunoglobulin production. TH₂ T cells also secrete a range of cytokines:

T_H2 cells help [[B cells]] produce antibody where the organism is present in tissue fluid. The T_H2 population influences B cell activation, proliferation and immunoglobulin production. T_H2 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-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-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.

#'''IL-6'''  also activates B cells, stimulates a high rate of proliferation and promotes immunoglobulin synthesis.

==Common Functions of TH₁ and TH₂ Cells==

==Common Functions of T_H1 and T_H2 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]]'''.

Both T_H1 and T_H2 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 T_H subset is '''cytokine-controlled reactive [[Haematopoiesis - Overview|haematopoiesis]]'''.

 

==Cytotoxic T-Cells==

==Cytotoxic T-Cells==

==T-Helper Cell Function==

==T-Helper Cell Function==

[[Image:TH1-2.jpg|thumb|right|200px|TH1 and 2 selection is influenced by infection - B. Catchpole, RVC 2008]]

[[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.

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 T_H 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 and TH₂ cells) secrete different sets of cytokines.

TH cells secrete cytokines for only a short period after they have been activated; the range of cytokines that T_H cells secrete after activation chiefly determines their function. Different T-helper cell subpopulations (T_H1, T_H2 and T_H17 cells) secrete different sets of cytokines.

 

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{{Jim Bee 2007}}

{{Jim Bee 2007}}

[[Category:Lymphocytes|E]]

[[Category:Lymphocytes|E]]

[[Category:Adaptive Immune System|C]]

[[Category:Adaptive Immune System|C]]