Immuno T Cell Maturatino In The Thymus

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The thymus also possesses a dendritic like cell population known

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nurse cells

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Also have macrophages and variety of epithelial cells. These support cells express These cells also provide the thymocytes with a variety of

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-high levels of both class I and II chains for peptide presentation to the maturing T cell’s TCR complex.
-T cell promoting compounds that help these cells proliferate (growth factors, etc).

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1.The most immature cells of thymus do not possess CD3 (and thus TCR) but do express other markers including

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Thy-1.

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The first observed change is that these cells begin their TCR rearrangement pathway.

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Gamma/delta chains re-arrange first. In a second lineage of T cells, alpha/beta next. Most available data suggests that there are two distinct lineages of T cells: one that express alpha/beta, the second with gamma/delta

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Once the TCR genes start rearranging,

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the transcription of the CD3 components is stimulated such that all of the primary components of the CD3/TCR complex are made together.

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what lets a t cell survive?

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So correct engagement of the TCR actually induces the cells to survive

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Instructional model.

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Epithelial cells that are part of the thymus framework express both class I and II.
Concept is that the double positive cells will bind to either I or II MHC with TCR.
If get close enough match with TCR, the CD4 or 8 chains engage as well.
This leads to the loss of the un-utilized chain (either CD4 or CD8) and enrichment of the TCR that binds self.

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Stochastic model

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Utilizes concept that the double positive cells randomly lose the expression of either the CD4 or CD8 chain. This loss then leaves the cell as TCR/CD8 or TCR/CD4. Must engage a class I or class II bearing cell correctly or the T cell dies.

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a) if the naïve T cell is activated in the presence of IL-4

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will commit to a TH2 lineage

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b) if the naïve T cell is activated in the presence of IL-12,

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will commit to a TH1 lineage

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TH1 cells primarily produce which drives

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IFN-gamma
-the antibacterial, inflammatory response: production of opsonizing isotypes of antibody (bound by Fc receptor and efficient at complement activation), activation of macrophages, enhanced CTL, NK and neutrophil killing.

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TH2 cells primarily product IL-5 leads to

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IL-4, with IL-5 and IL-10. Isotypes are neutralizing and part of the allergic response,
-eosinophil proliferation and activation, and macrophages are pushed into an anti-inflammatory status.

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, TH1/TH2 phenotypes can also be ascribed to

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CTL, dendritic cells, mast cells, e