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==Introduction==
==Introduction==
Within the blood and lymphoid organs the majority of CD4+ T cells are antigen-naive T-cells. There is only a small proportion of memory T-cells.
Within the blood and lymphoid organs the majority of [[Lymphocytes - WikiBlood#Helper CD4+|CD4+ T cells]] are antigen-naive T-cells. There is only a small proportion of memory T-cells.
Naive T-cells have yet to encounter antigen and can only be activated by antigen presented by dendritic cells. After initial antigenic activation, naïve T-cells develop into an intermediate stage cell called the TH<sub>0</sub> cell which can then be activated by any antigen-presenting cell, e.g. Dendritic cell, macrophage or B-cell.
Naive T-cells have yet to encounter antigen and can only be activated by antigen presented by dendritic cells. After initial antigenic activation, naïve T-cells develop into an intermediate stage cell called the TH<sub>0</sub> cell which can then be activated by any antigen-presenting cell, e.g. Dendritic cell, [[Macrophages - WikiBlood|macrophage]] or [[Lymphocytes - WikiBlood#B cells|B-cell]].
The TH<sub>0</sub> cells have the capacity to differentiate into TH<sub>1</sub> and TH<sub>2</sub> cells. The type of cell that develops depends on the antigen presenting cell. Macrophages cause the TH<sub>0</sub> cell to develop into TH<sub>1</sub> cells caused by IL-12 production following macrophage-antigen interaction. B-cells cause the TH<sub>0</sub> cell to develop into TH<sub>2</sub> cells caused by IL-10 production following B-cell-antigen interaction. On antigenic stimulation the TH<sub>1</sub> or TH<sub>2</sub> cells become activated, undergo clonal expansion and secrete a range of different cytokines.
The TH<sub>0</sub> cells have the capacity to differentiate into TH<sub>1</sub> and TH<sub>2</sub> cells. The type of cell that develops depends on the antigen presenting cell. [[Macrophages - WikiBlood|Macrophages]] cause the TH<sub>0</sub> cell to develop into TH<sub>1</sub> cells caused by IL-12 production following [[Macrophages - WikiBlood|macrophage]]-antigen interaction. [[Lymphocytes - WikiBlood#B cells|B-cells]] cause the TH<sub>0</sub> cell to develop into TH<sub>2</sub> cells caused by IL-10 production following B-cell-antigen interaction. On antigenic stimulation the TH<sub>1</sub> or TH<sub>2</sub> cells become activated, undergo clonal expansion and secrete a range of different cytokines.
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 antigen disappears.
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 [[Lymphocytes - WikiBlood#T cells|T cells]] continues until antigen disappears.
==Dendritic Cells==
==Dendritic Cells==
* Cytokines secreted include:
* Cytokines secreted include:
** '''IL-2'''.
** '''IL-2'''.
*** Gives proliferation of both CD4+ and CD8+ T-cells.
*** Gives proliferation of both [[Lymphocytes - WikiBlood#Helper CD4+|CD4+]] and [[Lymphocytes - WikiBlood#Cytotoxic CD8+|CD8+ T-cells]].
*** This stimulation of proliferation of T-cells is the main function of the TH<sub>1</sub> cell.
*** This stimulation of proliferation of [[Lymphocytes - WikiBlood#T cells|T cells]] is the main function of the TH<sub>1</sub> cell.
** '''Interferon gamma''' ('''IFNγ''').
** '''Interferon gamma''' ('''IFNγ''').
*** Activates tissue macrophages
*** Activates tissue macrophages
==TH<sub>2</sub> Cells==
==TH<sub>2</sub> Cells==
* The TH2 population influences B-cell activation, proliferation and immunoglobulin production.
* The TH2 population influences [[Lymphocytes - WikiBlood#B cells|B cell]] activation, proliferation and immunoglobulin production.
* The TH2 T cell population secrete a range of cytokines.
* The TH2 [[Lymphocytes - WikiBlood#T cells|T cell]] population secrete a range of cytokines.
** '''IL-4'''
** '''IL-4'''
*** Stimulates B cell growth.
*** Stimulates [[Lymphocytes - WikiBlood#B cells|B cell]] growth.
*** Gives heavy chain switch from IgM to IgG , IgA and IgE.
*** Gives heavy chain switch from [[Immunoglobulin M - WikiBlood|IgM]] to [[Immunoglobulin G - WikiBlood|IgG]] , [[Immunoglobulin A - WikiBlood|IgA]] and [[Immunoglobulin E - WikiBlood|IgE]].
*** Proliferation of basophils/ mast cells.
*** Proliferation of basophils/ mast cells.
*** Can inhibit some T-cell responses.
*** Can inhibit some [[Lymphocytes - WikiBlood#T cells|T cell]] responses.
** '''IL-5'''
** '''IL-5'''
*** Activates B-cells.
*** Activates [[Lymphocytes - WikiBlood#B cells|B cells]].
*** Stimulates high rate B-cell proliferation.
*** Stimulates high rate [[Lymphocytes - WikiBlood#B cells|B cells]] proliferation.
*** Promotes immunoglobulin synthesis.
*** Promotes immunoglobulin synthesis.
*** Proliferation and differentiation of eosinophils.
*** Proliferation and differentiation of eosinophils.
** '''IL-6'''
** '''IL-6'''
*** Activates B-cells.
*** Activates [[Lymphocytes - WikiBlood#B cells|B cells]].
*** Stimulates high rate B-cell proliferation.
*** Stimulates high rate [[Lymphocytes - WikiBlood#B cells|B cell]] proliferation.
*** Promotes immunoglobulin synthesis.
*** Promotes immunoglobulin synthesis.
==Common Functions of Th<sub>1</sub> and TH<sub>2</sub> Cells==
==Common Functions of Th<sub>1</sub> and TH<sub>2</sub> Cells==
* Both TH1 and TH2 cells produce IL-3 and granulocyte-macrophage colony stimulating factor (GM-CSF).
* Both TH1 and TH2 cells produce IL-3 and granulocyte-[[Macrophages - WikiBlood|macrophage]] colony stimulating factor (GM-CSF).
** These act to activate and induce proliferation of neutrophils and also macrophages.
** These act to activate and induce proliferation of [[Neutrophils - WikiBlood|neutrophils]] and also [[Macrophages - WikiBlood|macrophages]].
*** Neutrophils are the major phagocytic cells in the blood and the principal cells in acute inflammatory lesions.
*** [[Neutrophils - WikiBlood|Neutrophils]] are the major phagocytic cells in the blood and the principal cells in acute inflammatory lesions.
**** Function chiefly in the defence against extracellular bacteria.
**** Function chiefly in the defence against extracellular bacteria.
** Therefore, one of the major biological functions of the activation of either TH subset is cytokine-controlled reactive haematopoiesis.
** Therefore, one of the major biological functions of the activation of either TH subset is cytokine-controlled reactive [[Overview of Haematopoiesis - WikiBlood|haematopoiesis]].
==Cytotoxic T-Cells==
==Cytotoxic T-Cells==
* Viruses are intracellular pathogens that use the host cell machinery for pathogen protein synthesis.
* Viruses are 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.
** Viral peptides associate with MHC class I and are expressed on the cell surface.
*** CD8+ cytotoxic T-lymphocytes (CTL) recognise the antigen-MHC complex.
*** [[Lymphocytes - WikiBlood#Cytotoxic CD8+|CD8+ cytotoxic T-lymphocytes (CTL)]] recognise the antigen-MHC complex.
* Cytotoxic T-cells secrete a pattern of cytokines similar to that of TH<sub>1</sub> cells.
* Cytotoxic T-cells secrete a pattern of cytokines similar to that of TH<sub>1</sub> cells.
** I.e. IFNγ but not IL-2.
** I.e. IFNγ but not IL-2.
*** The IFNγ shifts the balance of the immune response in favour of TH<sub>1</sub> cells.
*** The IFNγ shifts the balance of the immune response in favour of TH<sub>1</sub> cells.
**** There is therefore an increased level of T-cell proliferation.
**** There is therefore an increased level of [[Lymphocytes - WikiBlood#T cells|T-cell]] proliferation.
***** The initiation of the immune response via CTL leads to the selective proliferation of CTL - enhances the main mechanism of killing of virally-infected cells.
***** The initiation of the immune response via CTL leads to the selective proliferation of CTL - enhances the main mechanism of killing of virally-infected cells.
==T-Cell Activation==
==T-Cell Activation==
* T-cells function only after recent activation by antigen.
* [[Lymphocytes - WikiBlood#T cells|T cells]] function only after recent activation by antigen.
* CD4 binds MHC class II.
* CD4 binds MHC class II.
** CD4+ T-cells therefore recognise antigen only in association with MHC class II
** [[Lymphocytes - WikiBlood#Helper CD4+|CD4+ T-cells]] therefore recognise antigen only in association with MHC class II
* CD8 binds MHC class I.
* CD8 binds MHC class I.
** CD8+ T-cells recognise antigen only in association with MHC class I.
** [[Lymphocytes - WikiBlood#Cytotoxic CD8+|CD8+ T-cells]] recognise antigen only in association with MHC class I.
* Activation of T cells requires two distinct signals.
* Activation of [[Lymphocytes - WikiBlood#T cells|T cells]] requires two distinct signals.
** '''Signal 1'''
** '''Signal 1'''
*** The interaction of the TcR with the antigenic peptide/MHC complex on the antigen presenting cell.
*** The interaction of the TcR with the antigenic peptide/MHC complex on the antigen presenting cell.
** '''Signal 2'''
** '''Signal 2'''
*** The interaction of CD28 on the T-cell with its ligand, CD80, on the antigen-presenting cell.
*** The interaction of CD28 on the [[Lymphocytes - WikiBlood#T cells|T cells]] with its ligand, CD80, on the antigen-presenting cell.
**** APC expression of CD80 only occurs after:
**** APC expression of CD80 only occurs after:
***** The engagement of pattern recognition or Fc receptors.
***** The engagement of pattern recognition or Fc receptors.
* '''No signal 1'''
* '''No signal 1'''
** T-cell is not activated as there is no antigen.
** [[Lymphocytes - WikiBlood#T cells|T cells]] is not activated as there is no antigen.
* '''Both signal 1 and signal 2'''
* '''Both signal 1 and signal 2'''
** T-cell is activated into clonal expansion.
** [[Lymphocytes - WikiBlood#T cells|T cells]] is activated into clonal expansion.
*** Produces cytokines or becomes cytotoxic.
*** Produces cytokines or becomes cytotoxic.
** This is the response to a dangerous antigen.
** This is the response to a dangerous antigen.
===Response to Activation===
===Response to Activation===
* The response of the T cells to obtaining Signals 1 and 2 is:
* The response of the [[Lymphocytes - WikiBlood#T cells|T cells]] to obtaining Signals 1 and 2 is:
** To express the receptor for the cytokine interleukin-2 (IL-2).
** To express the receptor for the cytokine interleukin-2 (IL-2).
** In CD4+ T-cells only, the secretion of IL-2.
** In [[Lymphocytes - WikiBlood#Helper CD4+|CD4+ T-cells]] only, the secretion of IL-2.
* The final trigger for clonal expansion is the engagement of IL-2R with IL-2.
* The final trigger for clonal expansion is the engagement of IL-2R with IL-2.
** The IL-2 can come from any activated CD4+ T-cell.
** The IL-2 can come from any activated CD4+ T-cell.