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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]] | + | {{OpenPagesTop}} |
− | [[Image:T Cell diagram 2.jpg|thumb|right|150px|T Cell - Copyright Prof Dirk Werling DrMedVet PhD MRCVS]]
| + | [[Image:TCR2.jpg|thumb|right|300px|T-cell receptor binds antigen fragments presented by MHC on the cell surface - B. Catchpole, RVC 2008]] |
− | ''Also called T lymphocytes'' | + | Also known as '''T lymphocytes'''<br /> |
− | <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+=== | + | ''See also: [[T cell differentiation|T cell differentiation]]'' |
− | <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. | + | ==Introduction== |
− | *Th1 cells produce Il-2, IFN-γ and TNF-α
| + | <p>T cells are 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 major histocompatability complex (MHC) II.</p><p>Functionally they are divided into three subsets that are distinguished by the 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> |
− | *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> | |
− | <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#TH1 Cells|here]]
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− | ===Cytotoxic CD8<sup>+</sup>=== | + | ==T-cell receptors== |
− | <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: | + | [[Image:T Cell diagram 2.jpg|thumb|right|305px|T Cell - Copyright Prof Dirk Werling DrMedVet PhD MRCVS]] |
| + | T-cell receptors are the antigen-specific receptors for T-lymphocytes, and are a combination of either α/β chains or γ/δ chains; one T-cell will express either α/β or γ/δ TCRs. The antigen-binding site of the TCR is produced by a combination of the V domains of the relevant chain. Like antibody, the specificity of the TCR is determined by the '''amino acid composition of the variable domains'''. |
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| + | TCRs are linked to the cell membrane; structurally, they look like a single arm of an antibody molecule consisting of a distal domain and a membrane proximal constant domain |
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| + | ==Helper CD4<sup>+</sup>== |
| + | <p>These T cells express the marker CD4 and are categorised into three groups, T<sub>H</sub>1 and T<sub>H</sub>2, with a third lineage, T<sub>H</sub>17 being recently described. These lineages are distinguished by the cytokines they produce. T helper cells recognise antigens bound to MHC II complexes. |
| + | *T<sub>H</sub>1 cells produce IL-2, IFN-γ and TNF-α |
| + | *T<sub>H</sub>2 cells produce IL-4, IL-5, IL-10 and IL-13 |
| + | *T<sub>H</sub>17 cells produce IL-17, IL-17F, IL-21 |
| + | T<sub>H</sub>1 cells interact with CD8<sup>+</sup>, NK and dendritic cells and T<sub>H</sub>2 cells interact with B cells. T<sub>H</sub>1 cells are involved with the control of intracellular pathogens and T<sub>H</sub>2 cells extracellular pathogens. IL-2 produced by T<sub>H</sub>1 cells stimulates further proliferation of CD4<sup>+</sup> cells. T<sub>H</sub>17 cells are produced to enhance innate immunity, with the cytokines produced increasing the extravasation of neutrophils.</p> |
| + | <p>T<sub>H</sub>0 populations are CD4<sup>+</sup> cells that have yet to differentiate into T<sub>H</sub>1, T<sub>H</sub>2 or T<sub>H</sub>17 cells and they secrete IL-2, IL-4, IL-5, IFN-γ. In the presence of IL-4 they develop into T<sub>H</sub>2 cells while in the presence of IL-2 they develop into T<sub>H</sub>1 cells. In the abscence of IL-2 T<sub>H</sub>1 cells will change into T<sub>H</sub>2 cells. T<sub>H</sub>17 cells develop in the presence of TGF-β and IL-6 and can further develop into T<sub>H</sub>1 cells depending on various conditions. </p> |
| + | <p>T<sub>H</sub>1 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 cells that do not secrete IFN-γ are termed '''memory T cells'''</p> |
| + | <p> T cell differentiation is a field of continual change, with discoveries made on a regular basis. </p> |
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| + | ==Cytotoxic CD8<sup>+</sup>== |
| + | <p>These T cells express the marker CD8 and once fully mature seek and destroy target cells (infected or neoplastic 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 -for example with a viral infection, viral peptides associate with MHC I and the CD8<sup>+</sup> T cell recognises this and binds to the infected cell. Only two pathways are used by cytotoxic T cells to kill cells: |
| *One pathway uses the CD95 (death receptor) which triggers apoptosis in the target cell (usually other T cells) | | *One pathway uses the CD95 (death receptor) which triggers apoptosis in the target cell (usually other T cells) |
| *The other pathway uses perforins and granzymes which form pores in the target cell membrane causing cell lysis | | *The other pathway uses perforins and granzymes which form pores in the target cell membrane causing cell lysis |
− | **Perforins are structurally related to complement factor C9 | + | **Perforins are structurally related to [[Complement#Membrane Attack Complex|complement factor C9]] |
| **Granzymes are proteolytic enzymes that target cell nucleases and cause apoptosis | | **Granzymes are proteolytic enzymes that target cell nucleases and cause apoptosis |
− | 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> | + | 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 T<sub>H</sub>1 cells i.e. IFN-γ but not IL-2. IFN-γ shifts the balance of the immune response in favour of TH<sub>1</sub> 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===
| + | ==γδ cells== |
| <p>''Information on these cells is varied.''</p> | | <p>''Information on these cells is varied.''</p> |
| <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> | | <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> |
| <p>The cells can be divided into two subsets: | | <p>The cells can be divided into two subsets: |
| *One with restricted antigen binding, that act as first line defence against invading organisms and recognises antigens bound to MHC I complex | | *One with restricted antigen binding, that act as first line defence against invading organisms and recognises antigens bound to MHC I complex |
− | *The other subset doesn’t require the MHC complex and this subset has a further two subsets | + | *The other subset doesn’t require the MHC complex and this subset has two further divisions |
− | ** One producing cytokines and chemokines (Th1 and Th2) | + | ** One producing cytokines and chemokines (T<sub>H</sub>1 and T<sub>H</sub>2) |
| **The other having cytotoxic effects.</p> | | **The other having cytotoxic effects.</p> |
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| + | {{Jim Bee 2007}} |
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− | [[Category:Lymphocytes|B]] | + | {{OpenPages}} |
| + | [[Category:Lymphocytes|D]] |