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DiGeorge Syndrome
- deletion chromosome22
- absent thymus, parathyroids, cardiac and facial abnormalities
- opportunistic infections
- tetany due to hypocalcemia
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First signal of T cell activation
Binding of TCR + Cd4 or Cd8 to MHC + antigen
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Second signal of T cell activation
binding of B7 on APC with CD28 on T cell
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Activation of T-cells leads to the production of what 3 transcription factors
NFAT, NF-KB, AP-1
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NFAT, NF-KB, and AP-1 lead to what expression
- IL-2 and high affinity IL-2R in the T-cell
- IL-2 binding activates JAK/STAT resulting in synthesis of cyclins which leads to T-cell proliferation
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CTLA-4 is what
receptor on activated T cells binds B7 on APC, inhibits proliferation
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Cyclosporin and Tacrolimus
inhibit calcineurin, prevent NFAT generation, prevent IL-2 expression, suppress immune system
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Th1
1. target
2. activating cytokines
- 1. bacteria, fungus, virus
- 2. IL-12 and IFN-y
- activated macrophages secrete IL-12 activate NK cells, they secrete IFN-y activate Th to Th1 cells they secrete IFN-y
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Th2
1. target
2. activating cytokines
- 1. Parsites and allergens
- 2. IL-4
- IL-4 is secreted by Th cells in the absense of another IL, it is also secreted by mast cells when parasites are around
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Th17
1. target
2. activating cytokines
- 1. unknown
- 2. IL-6 and TGF-B
- IL-6 is a proinflammatory and TGF-B is secreted at mucosal surfaces, they lead t cells to secrete IL-21 which leads to Th17 conversion
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effector Th1 cells
1. secrete
2. function
- 1. IL-2, IFN-y, TNF, CD40L
- 2. intracellular infections, CMI response
- -activate macrophages (IFN-y and CD40L)
- -stimulate Bcells to produce IgG opsinizing antibodies (IFN-y)
- -activate CTL's (IL-2 and IFN-y)
- -increase CAM and chemokine expression on vascular endothelium (TNF)
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effector Th2 cells
1. secrete
2. function
- 1. IL-4, IL-13 (same fcn) IL-5, IL-10
- 2. stimulate Bcells to produce non-opsonizing ab IgE, protect against helminthic infections, inhibit macrophages
- -if Th2 response dominates when Th1 should problems occur (leprosy)
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effector Th17 cells
1. secrete
2. function
- 1. IL-17, IL-21, IL-22
- 2. aid in inflamation response
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effetor Tc cells (CTL's)
function and 2 methods
- kill infected cells or cancer cells
- 1. degranulation
- 2. Fas-FasL
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explain degranulation from CTL's
- perforin monomers form channel on cell
- granzymes (serine esterases) enter cell and activate apoptotic patway
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Explain Fas-FasL
Fas on all nucleated cells interacts with FasL on CTL to activate the apoptotic caspase pathway
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2 types of memory T cells and function
- 1. Central memory Tcells, home in secondary lymphoid, proliferate quickly on exposure and generate more T cells
- 2. Effector memory Tcells, home in peripheral tissues, secrete cytokines on activation but don't proliferate
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