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38 terms

L13 Regulation of Immunity

IL-2 stimulates
T cell diff
IL-12 drives T cell diff toward
(prod by macros)
IL-4 drives T cell diff toward
Ig of 1º response?
Ig of 2º response?
Treg cells are CD___+
T cell release ____ that drives B cell prolif
What is immunologic tolerance?
"unresponsiveness to self antigens"
What percentage of cells dev't from hematopoetic precursors never make it to maturity?
Central tolerance
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
CTLA-4 is found on _, and binds _
• T cells
• B7 on APCs (↑ p microbe encounter)
• inhibitory fn
CD28 is found on _, and binds _
• T cells
• B7 on APCs (↑ p microbe encounter)
• stim fn
CD40L is found on _, and binds _
• activated T cells
• CD40 on B cells
LFA-1 is found on _, and binds _
• T cells
• ICAM-1 on APCs
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
in vivo anergy
an adaptation to persistent Ag
Clonal anergy
growth arrest state that maintain cell in G1, even p full TCR stim
High [IL-2] → ↑ sensitivity of ____ T cells to Fas mediated _____
• Ag-stim
• apoptosis
Possible that Ag-binding causes T cells to produce _____, while costim produces _____, so lack of costimulation causes apoptosis.
• pro-apoptotic proteins
• anti-apoptotic proteins
CD25+ is
• expressed in high levels by Treg
• the α chain of IL-2 receptor
Tregs produce
• IL-10 and TGF-β
• which block activation of T cells and macros
IL-2 first binds ____ of the IL-2 receptor with low affinity, then ___ contributes to binding and engages Jak3-STAT5-dependent signal transduction pathway
• IL-2Rα
• IL2/15Rβ
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
common γ
IL2Rα is newly induced by...
• naive T cell activation
• also causes upregulation of IL-2Rβ
Chronic T cell stim results in shedding of ___, which can be used as a marker of strong antigenic stim (e.g. acute graft rejection)
What are the roles of CTLA-4 and Treg inhibition in CD8+ cells?
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
• 2:1
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
T-independent antigens always yield Ig_ and form memory B cells with what frequency?
• M
• never