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caused by anergy (functional unresponsiveness) or apoptosis of immature cells that are self-reactive
Foreign antigens are presented at the...
2º lymphoid organs: spleen, lymph nodes, Peyer's patches....
Peripheral tolerance: T cell that recognize self antigen in peripheral tissue...
1. apoptosis, or
2. anergy, or
3. Treg suppression
Anergy is caused by
• +1st signal: antigen recognition, but -2nd signal: costimulation (or suppressor costim, e.g. CTLA-4), or
• low affinity peptide ligand
Repeated activation of T cells by self-ag or recognition of self-ag s 2nd signal stimulates...
In CD4+ T cells, repeated activation results in co-expression of ___ and ___, which causes ____
• Fas (CD95) and FasL- death receptor
• apoptosis caused by caspase activation when Fas-FasL bind; can occur with itself or nearby cell
Possible that Ag-binding causes T cells to produce _____, while costim produces _____, so lack of costimulation causes apoptosis.
• pro-apoptotic proteins
• anti-apoptotic proteins
IL-2 first binds ____ of the IL-2 receptor with low affinity, then ___ contributes to binding and engages Jak3-STAT5-dependent signal transduction pathway
The ____ chain of the IL-2 receptor does not directly bind IL-2, but is required for high affinity binding and activation of signal transduction pathways
Chronic T cell stim results in shedding of ___, which can be used as a marker of strong antigenic stim (e.g. acute graft rejection)
Receptor editing is the process by which B cells in the marrow which interact with self- antigens change their...
• antigen specificity, by gene recombination of the light chain
• associates with OLD HEAVY CHAIN (no class ∆)
Ig light chain is made of either ___ or ___ chains, which in the mature human are in a ratio of ___.
• κ and λ
How is it determined that a B cell in the marrow that is highly self-binding is apoptosed or receptor edited?
Immature B cell first expresses light chain, resulting in sIgM with ____ still expressed.
• RAG-1, -2 (recombo activating genes)
If strong sIgM cross-linking does not occur, gene rearrangement ____ and RAG protein (↑/↓)
• gene rearrangement ceases
• RAG protein declines (but does not cease until maturity)
If there is strong sIgM cross-linking, development is ___ and RAG expression ____
• development is halted
• RAG expression continues @ level c/w light-gene chain rearrangement
• recombinase causes rearrangements
Receptor editing recombinase action
• fast, keeps going until not auto-reactive or VJ segments depleted
• If still auto-reactive cell apoptoses
• if κ exhausted, will try λ
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