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38 terms

L13 Regulation of Immunity

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IL-2 stimulates
T cell diff
IL-12 drives T cell diff toward
Th1
(prod by macros)
IL-4 drives T cell diff toward
Th2
Ig of 1º response?
IgM
Ig of 2º response?
IgG
Treg cells are CD___+
CD4+/CD25+
T cell release ____ that drives B cell prolif
IL-4
What is immunologic tolerance?
"unresponsiveness to self antigens"
What percentage of cells dev't from hematopoetic precursors never make it to maturity?
95%
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...
apoptosis
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)
IL-2Rα
What are the roles of CTLA-4 and Treg inhibition in CD8+ cells?
UNCLEAR
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?
unknown
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