Immunological Tolerance and Autoimmunity Flashcards
What is the difference between central tolerance and peripheral tolerance?
Central: induced in immature self-reactive lymphocytes in the primary lymphoid organs. Ensures that lymphocytes are not reactive to self-Ags.
Peripheral: induced in mature self-reactive lymphocytes in the lymph nodes or peripheral sites. Needed to prevent activation of potentially dangerous lymphocyte clones in the periphery.
What surface molecules do Tregs typically express?
CD4, CD25, and CTLA-4
What is the Treg transcription factor?
FOXP3
What cytokine is critical for the survival and functional competence of Treg cells?
IL-2
What are induced Treg cells (iTreg cells)?
Mature Th0 cells (naive CD4 cells) outside the thymus (lymph nodes and GI tract) that acquire the Treg phenotype and function.
How is the development of iTregs and Th17 cells related?
If there is antigen recognition in the presence of TGF-β and without the presence of IL-6, then FOXP3 is expressed, leading to iTreg differentiation. If there is antigen recognition in the presence of both TGF-β and IL-6, then RORγt is expressed, leading to Th17 cell differentiation.
How do T cells become anergic and suppressed?
Antigen recognition without adequate CD80:CD28 costimulation induces anergy. T cells may also engage inhibitory receptors CTLA-4 or PD-1 that suppresses T cell response. Occurs in the periphery.
What typically happens to B cells when they weakly recognize self antigens in the bone marrow?
They become anergic
What do all B cells that underwent BCR editing contain?
A λ light chain instead of a κ light chain.
What happens to mature B cells that recognize self Ag in peripheral tissues in the absence of specific Th cells?
They become unresponsive or die by apoptosis via phosphorylation of CD22 inhibitory receptor by Lyn and recruitment of SHP-1 tyrosine phosphatase. Defects in these molecules can lead to autoimmunity.
Where do Tregs regulate B cells?
In central and peripheral tissues
How to GI and skin microflora suppress pathobionts?
Though induction of regulatory immune responses involving Treg cells and IL-10.
What is autoimmune regulator (AIRE)?
A transcription factor that plays a key role in the presentation of peripheral tissue-restricted self antigens to T cells in the thymus. Mutations in AIRE causes breakdown of central tolerance and failure of negative selection.
What is the role of CTLA-4?
To provide signals that terminate immune responses and maintain self-tolerance. Expression is low in resting cells until activated by Ag. Once expressed, it terminates continuing activation of these cells.
Describe the difference between the cell-intrinsic vs cell-extrinsic functions of CTLA-4.
Intrinsic: CTLA-4 on T cell delivers inhibitory signals that terminate further activation of that cell.
Extrinsic: CTLA-4 on Treg cells or responding T cells bind to B7 (CD80) molecules on APCs, blocking costimulation via B7 on nearby T cells.
