Lecture 24: Tolerance and Autoimmunity Flashcards
state of specific unresponsiveness to an antigen induced by prior exposure to that antigen
immune tolerance
tolerance is an active process
How does the immune system address inevitable reactivity to self
Elimination of self-reactive T cells in the thymus: Central tolerance
Failure to provide the signals to induce a T cell response: Peripheral tolerance
what is AIRE (autoimmune regulator)
transcription factor that facilitates expression of non-thymic proteins in the thymus to test reactivity
_____ anergy is initiated when T-cells are exposed to antigen in the absence of costimulation
Clonal
what is the mechanism of clonal anergy
suppression of NFKB and decreased production of cytokines (IL-2)
lasts for several weeks
what is immune paralysis
high doses of antigen that bypass APCs, bind TCR directly, lack costimulation and induce paralysis
antigen dose affects ____ of tolerance
induction
Very low doses of antigen fail to send a sufficient signal, inadequate co-stimulation occurs
very high doses can overstimulate the cells and initiate peripheral tolerance
where and when does central tolerance of B-cells occur
occurs in bone marrow once B-cell can express IgM (immature B cell)
random somatic mutations of B-cells occur in __________ organs, and must be controlled peripherally
secondary lymphoid
what things cause mature B cells to undergo peripheral tolerance
chronic antigen recognition
absence of costimulation
excessive suppressor cell activity
excessive T-independent antigen
once an antigen is eliminated, tolerance….
subsides
bone marrow activity (production of new cells) ______tolerance
reduces
immunosuppressive drugs _______ tolerance
prolong
______drive the immune response, _______turn it off
antigens, antibodies
antibodies have a feedback loop on _____cells to ______further production of antibodies
Bcells, inhibit
______antibodies inhibit antibody production in the newborn
maternal
Adaptive immune responses are _______Driven
antigen
adaptive immune response is initiated only when…? when does it cease?
initiated only on exposure to antigen
ceases when antigen eliminated
what happens when self or other antigens don’t reach lymphoid tissue
fail to induce immunity to tolerance
self antigens form immune privledged sites
the effect of antigen can be modulated by…?
adjuvants
antibodies suppress _____cell responses
B
IgM suppresses only..?
IgM