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| | + | ==[[T cells]]== |
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| − | ==T cells==
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| − | [[Image:TCR2.jpg|thumb|right|150px|T-cell receptor binds antigen fragments presented by MHC on the cell surface - B. Catchpole, RVC 2008]]
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| − | [[Image:T Cell diagram 2.jpg|thumb|right|150px|T Cell - Copyright Prof Dirk Werling DrMedVet PhD MRCVS]]
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| − | ''Also called T lymphocytes''
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| − | <p>So named as they differentiate in the [[Thymus - Anatomy & Physiology|thymus]]. They are long lived and are involved in cell mediated immunity. They represent 60-80% of the circulating lymphocytes and all express the markers CD2, CD3 and CD7 as well as having T cell receptors (TCR). Each T cell has 30,000 TCRs each of which is identical and recognises antigens and MHC II.</p><p>Functionally they are divided into three subsets that are distinguished by presence or absence of CD4 or CD8 markers. CD4 and CD8 cells have α/β antigen receptors while the γδ cells have the γ/δ antigens receptors.</p>
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| − | * T-cell receptors are the antigen-specific receptors for T-lymphocytes
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| − | * T-cell receptors are a combination of either αβ chains or γδ chains
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| − | ** One T-cell will express either αβ OR γδ TCR
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| − | * The antigen-binding site of the TCR is produced by a combination of the V domains of either 1α and 1β chain or 1γ and 1δchain
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| − | ** Like antibody, the specificity of TCR is determined by the '''amino acid composition of the variable domains'''
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| − | * TCR are '''always''' linked to the cell membrane
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| − | * Like antibody, TCR consist of a distal domain and a membrane proximal constant domain
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| − | ** Structurally, they look like a single arm of an antibody molecule
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| − | ===Helper CD4+===
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| − | <p>These T cells express the marker CD4 and are categorised into two groups, Th1 and Th2, which are distinguished by the cytokines they produce. T helper cells recognise antigens bound to MHC II complex.
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| − | *Th1 cells produce Il-2, IFN-γ and TNF-α
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| − | *Th2 cells produce Il-4, Il-5, Il-10 and Il-13
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| − | Th1 cells interact with CD8<sup>+</sup>, NK and dendritic cells and Th2 cells interact with B cells. Th1 cells are involved with the control of intracellular pathogens and Th2 cells extracellular pathogens. Il-2 produced by Th1 cells stimulates further proliferation of CD4<sup>+</sup> cells.</p>
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| − | <p>Th0 populations are CD4<sup>+</sup> cells that have yet to differentiate into Th1 or Th2 cells and they secrete Il-2, IL-4, Il-5, IFN-γ. In the presence of Il-4 they develop into Th2 cells while in the presence of Il-12 they develop into Th1 cells. In the abscence of Il-12 Th1 cells will change into Th2 cells.</p>
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| − | <p>Th1 cells have two populations. One that secretes IFN-γ and is short lived, and the other that doesn’t secrete IFN-γ and is long lived. The IFN-γ<sup>-</sup> cells are termed memory T cells (This relationship is not the case for Il-4<sup>+</sup> and Il-4<sup>-</sup> Th2 cells).</p>
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| − | <p>For more information on T helper cells click [[T cell differentiation - WikiBlood#TH1 Cells|here]]
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| − | ===Cytotoxic CD8<sup>+</sup>===
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| − | <p>These T cells express the marker CD8 and once fully mature seek and destroy target cells (infected or cancer forming cells). When the cytotoxic T cell recognises the MHC I complex on the target cell (MHC I binds to TCR) the T cell kills that cell e.g. viral peptides associate with MHC I and the CD8<sup>+</sup> T cell recognises this and binds to the cell. Only two pathways are used by cytotoxic T cells to kill cells:
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| − | *One pathway uses the CD95 (death receptor) which triggers apoptosis in the target cell (usually other T cells)
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| − | *The other pathway uses perforins and granzymes which form pores in the target cell membrane causing cell lysis
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| − | **Perforins are structurally related to complement factor C9
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| − | **Granzymes are proteolytic enzymes that target cell nucleases and cause apoptosis
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| − | In both cases direct contact is required between the T cell and target cell, and cell killing can take several minutes.</p><p> Cytotoxic T cells secrete a pattern of cytokines similar to that of TH1 cells i.e. IFN-γ but not IL-2. IFN-γ shifts the balance of the immune response in favour of TH1 cells giving an increased level of T cell proliferation. The initiation of the immune response via cytotoxic T cells leads to the selective proliferation of cytotoxic T cells enhancing the main mechanism of killing infected cells.</p>
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| − | ===γδ cells===
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| − | <p>''Information on these cells is varied.''</p>
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| − | <p>They do not express CD4 or CD8 and have γδ antigen receptors rather than α/β like other T cells. They develop in the [[Thymus - Anatomy & Physiology|thymus]] and migrate to epithelial tissues where they remain. The number present in an individual varies greatly but is generally greatest in immature ruminants and pigs.</p>
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| − | <p>The cells can be divided into two subsets:
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| − | *One with restricted antigen binding, that act as first line defence against invading organisms and recognises antigens bound to MHC I complex
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| − | *The other subset doesn’t require the MHC complex and this subset has a further two subsets
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| − | ** One producing cytokines and chemokines (Th1 and Th2)
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| − | **The other having cytotoxic effects.</p>
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| | [[Image:LH B cells Peyers Patch Histology.jpg|right|thumb|150px|<p>'''B Cells in Lymph node'''</p><sup>©RVC 2008</sup>]] | | [[Image:LH B cells Peyers Patch Histology.jpg|right|thumb|150px|<p>'''B Cells in Lymph node'''</p><sup>©RVC 2008</sup>]] |