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Lecture

BIOL 2005 Lecture Notes - Leishmania, Natural Killer Cell, Gata3

3 pages54 viewsFall 2012

Department
Biology
Course Code
BIOL 2005
Professor
Elizabeth Nisbet

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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 producedictate 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
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