15: Tolerance Flashcards
How does central tolerance work?
deletion and editing
Where does central tolerance occur?
thymus and bone marrow
How does antigen segregation work?
physical barrier to self-antigen access to lymphoid system
Where does antigen segregation occur?
peripheral organs (ex. thyroid, pancreas)
How does peripheral anergy work?
cellular inactivation by weak signaling without co-stimulus
Where does peripheral anergy occur?
secondary lymphoid tissue
How do regulatory T cells work?
suppression by cytokines, intercellular signals
Where does regulatory T cell self tolerance occur?
secondary lymphoid tissue and sites of inflammation
How does functional deviation work?
differentiation of regulatory T cells that limit inflammatory cytokine secretion
Where does functional deviation occur?
secondary lymphoid tissue and sites of inflammation
How does activation-induced cell death work?
apoptosis
Where does activation-induced cell death occur?
secondary lymphoid tissue and sites of inflammation
Positive selection
low affinity for self antigen in the thymus, thymocyte becomes a T cell
Negative selection
high affinity for self antigen in the thymus, thymocyte undergoes apoptosis
Agonist selection
intermediate affinity for self antigen in the thymus, thymocyte undergoes up-regulation of FoxP3 and becomes a Treg cell
Where in the thymus does negative selection occur?
cortex or medulla
AIRE
autoimmune regulator; transcriptional regulator expressed in mTECs that enables central tolerance to tissue-restricted antigens
3 major mechanisms of Treg suppression
- immuno-suppressive cytokines (IL-10, TGF-B)
- out-compete T effector cells for growth factors
- interfere with APCs’ ability to provide activating signals
Where do naive immune cells mostly circulate between?
blood and lymph
How is anergic tolerance induced?
APCs present self-antigen to T cell in the absence of inflammation
Receptor editing
self-reactive developing B cell continues light chain rearrangement, producing a new BCR
Absence of T cell help ____ B cell tolerance
facilitates
