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BLG 307 (38)
Clare Chua (38)


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BLG 307
Clare Chua

IMMUNOLOGY T CELL EFFECTOR I: CD4 + T CELLS AND CYTOKINES -antigen recognition of MHC/Ag on APC does not occur at site of entry, but usually in lymph nodes/spleen -activated T cells then migrate to target tissues -T cells then engage cells expressing appropriate Ag/MHC to exert functions (release INTERLEUKINS) -T cell subsets distinguished by MHC recognized and cytokines producedictate effector functions T-CELL PROLIFERATION IL2R – complex of αβγ that associate non-covalently to cell surface essential for immune function, as γ chains are involved in MANY ILR’s Note: Activation upregulates α to make high affinity complex Βγ already exists but is slow on slow off α is fast on/fast off Βγ α is fast on/slow off IL2 is not absolutely necessary b/c other cytokines can replace function BUT γ chain is b/c it is shared by the other cytokines XSCID-mutation in IL2-Rγ of jak 3 ag:MHC complex binding to TCR triggers IL2R assembly/synthesis ensures that IL2 only activates clonal expansion of ag-specific cells ag:MHC complex binding to TCR can also stimulate IL2 SYNTHESIS some cells can make IL2  autocrine/endogenous can be used can’t make IL2  paracrine/exogenous IL2 necessary other IL’s IL4 – growth factor, similar to IL2 IL7 – growth factor for immature T cells (CD4-, CD8-) in thymus produced by thymus stromal cells ILR’s are coupled to tyrosine kinases to initiate signaling cascade -ligand binding initiates receptor clustering to activate intracellular cytoplasmic tyrosine kinase IL-2Rβ chain associates with tyrosine kinases jak1 and Shc IL-2Rγ chain associates with jak 3 (CRITICAL for many ILs) -jak phosporylates STAT -STAT translocates to the nucleus to activate gene transcription CD4 CELL SUBCLASSES TH1 – synthesize IL2/3, TNFα, γ-INTERFERON -activates Mφ and enhances their ability to kill ingested microbes (bacteria, fungi, protozoa) 1) γ-inteferon is released in response to macrophage MHC II antigen presentation -needed to fight intracellular parasites that resist destruction and Ab response 2) CD40L(T cell) binds CD40 (macrophage) and/or TNF (T cell) interacts with TNF-R (macrophage) -these combined enhance macrophage lysosome-phagosome fusion and production of toxic O radicals and NO -enhanced macrophage ability is now INDEPENDENT of antigen PROOF- can transfer Ag specific activated T cells to fight Listeria and another pathogen simultaneously -Thus release of cytokines that mediate Mφ activation is Ag specific, but activated
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