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<big><center>[[Leukopoiesis - WikiBlood|'''BACK TO LEUKOPOIESIS''']]</center></big>
<big><center>[[Leukopoiesis - WikiBlood|'''BACK TO LEUKOPOIESIS''']]</center></big>
<big><center>[[Immunology - WikiBlood|'''BACK TO IMMUNOLOGY''']]</center></big>
===Development of CD4+ T-Cell Subpopulations===
* 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.
* Naive T-cells have yet to encounter antigen.
** can only be activated by antigen presented by dendritic cells.
* After initial antigenic activation, naïve T-cells develop into an intermediate stage cell.
** The TH<sub>0</sub> cell.
** Can then be activated by any antigen-presenting cell.
*** Dendritic cell, macrophage or 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.
*** For any one cell the cytokine-secreting activation state is short-lived.
**** 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.
===TH<sub>1</sub> Cells===
* TH<sub>1</sub> cells secrete a range of cytokines.
* Cytokines secreted include:
** '''IL-2'''.
*** Gives proliferation of both CD4+ and CD8+ T-cells.
*** This stimulation of proliferation of T-cells is the main function of the TH<sub>1</sub> cell.
** '''Interferon gamma''' ('''IFNγ''').
*** Activates tissue macrophages
*** Is the principal effector mechanism in the defence against intracellular bacteria and parasites.
**** E.g. Mycobacteria, Brucella, Rickettsia (bacteria) and Leishmania, Coccidia, Babesia (parasites).
**** Activates macrophages and stimulates them to produce enzymes triggering the intracellular killing mechanisms, e.g.
***** Superoxide dismutase and myeloperoxidase.
****** Produce H<sub>2</sub>O<sub>2</sub> and trigger the "superoxide burst".
***** Nitric oxide synthase.
****** Produces nitric oxide.
**** This is another example of the immune system working through the innate immune response.
*** Can act to suppress antibody synthesis.
===TH<sub>2</sub> Cells===
* The TH2 population influences B-cell activation, proliferation and immunoglobulin production.
* The TH2 T cell population secrete a range of cytokines.
** '''IL-4'''
*** Stimulates B cell growth.
*** Gives heavy chain switch from IgM to IgG , IgA and IgE.
*** Proliferation of basophils/ mast cells.
*** Can inhibit some T-cell responses.
** '''IL-5'''
*** Activates B-cells.
*** Stimulates high rate B-cell proliferation.
*** Promotes immunoglobulin synthesis.
*** Proliferation and differentiation of eosinophils.
** '''IL-6'''
*** Activates B-cells.
*** Stimulates high rate B-cell proliferation.
*** Promotes immunoglobulin synthesis.
===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).
** These act to activate and induce proliferation of neutrophils and also macrophages.
*** 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.
** Therefore, one of the major biological functions of the activation of either TH subset is cytokine-controlled reactive haematopoiesis.
==T-Cell Activation==
* T-cells function only after recent activation by antigen.
* CD4 binds MHC class II.
** CD4+ T-cells therefore recognise antigen only in association with MHC class II
* CD8 binds MHC class I.
** CD8+ T-cells recognise antigen only in association with MHC class I.
* Activation of T cells requires two distinct signals.
** '''Signal 1'''
*** The interaction of the TcR with the antigenic peptide/MHC complex on the antigen presenting cell.
** '''Signal 2'''
*** The interaction of CD28 on the T-cell with its ligand, CD80, on the antigen-presenting cell.
**** APC expression of CD80 only occurs after:
***** The engagement of pattern recognition or Fc receptors.
***** Activation with cytokines.
****** Interferons, IL-1β or TNFα.
**** Therefore '''signal 2 only occurs after the recognition of <font color=red>danger</font>'''.
===Scenarios===
* '''No signal 1'''
** T-cell is not activated as there is no antigen.
* '''Both signal 1 and signal 2'''
** T-cell is activated into clonal expansion.
*** Produces cytokines or becomes cytotoxic.
** This is the response to a dangerous antigen.
* '''Signal 1 but no signal 2'''
** T-cell is triggered into apoptosis and dies.
** This is the basis of "clonal deletion".
*** A major mechanism of tolerance.
*** Ensures that T-cells do not react with self (non-dangerous) antigens.
===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).
** In 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 IL-2 can come from any activated CD4+ T-cell.
** IL-2 produced by a CD4+ cell may also stimulate clonal expansion of that cell.
==T-Helper Cell Function==
* 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 secrete different sets of cytokines.
*** Th<sub>1</sub> and TH<sub>2</sub> cells.
==Links==
[[B Cell Differentiation - WikiBlood|B Cell Development]]
<big><center>[[Leukopoiesis - WikiBlood|'''BACK TO LEUKOPOIESIS''']]</center></big>
<big><center>[[Immunology - WikiBlood|'''BACK TO IMMUNOLOGY''']]</center></big>