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|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 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 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]]

T_H1 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".

''Still under investigation''

''Still under investigation''

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The T_H17 cells which form when T_H0 cells are challenged with IL-6 and TGF-β produce a number of cytokines that enhance the innate immune response. 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:

The T_H17 cells form when T_H0 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-17

*IL-17F

*IL-17F

*IL-6

*IL-6

*TNF-

*TNFα

*IL-21

*IL-21

*IL-22

*IL-22

*IL-23

*IL-23

Importantly they do not produce:

Importantly they do not produce:

IFN normally associated with T_H1 cells

*IFNγ normally associated with T_H1 cells

IL-4 normally associated with T_H2 cells

*IL-4 normally associated with T_H2 cells

==Cytotoxic T-Cells==

==Cytotoxic T-Cells==

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.

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]]