Lecture 24: Tolerance and Autoimmunity I Flashcards
(62 cards)
Immune tolerance
State of specific unresponsiveness to an antigen induced by prior exposure to that antigen
Why is tolerance important
Immune cells don’t attack self cells
How does immune system address reactivity to self
2 ways:
1. Central tolerance-elimination of self reactive T cells in thymus
2. Peripheral tolerance- failure to provide signals to induce T cell response
What is central tolerance
Elimination of self reactive T cells in the thymus
What is peripheral tolerance
Failure to provide signals to induce a T cell response
Anergy
Programmed nonresponsiveness
Negative selection
Elimination of T cells that bind strongly with self in thymus
Positive selection
Elimination of T cells that don’t bind or weakly bind to self-MHC
What is AIRE- autoimmune regulator
A transcription factor that facilitates expression of non-thymus proteins in thymus to test reactivity
What is clonal anergy
Initiated when T cells are exposed to antigen in absence of co-stimulation
What is the mechanism of suppression in peripheral tolerance
Suppress NFKB, decreased production of IL-2, decreased T cell production
What is immune paralysis
High dose of antigen that bypass APC’s bind TCR’s directly, lack of co-stimulation, induce paralysis
How does antigen dose affect induction of tolerance
Very low doses of antigen fail to send sufficient signal, inadequate co-stimulation (tolerance)
Moderate doses=immune response (antibody production)
High doses can overstimulate the cells and initiate peripheral tolerance (immune paralysis)
Where does B cell central tolerance occur
Bone marrow once B cells express IgM
Where does B cell peripheral tolerance occur
Secondary lymphoid organs
What is central tolerance of B cells
Immature B cell exposed to low doses of antigen will cause clonal abortion
What is peripheral tolerance in B cells
Mature B cell undergoes one of the following: exhaustive antigen challenge, absence of co-stimulation, excessive suppressor cell, excessive T-independent
Results in functional deletion and receptor blockade
If an antigen is eliminated tolerance ___
Subsides
If an antigen persists, tolerance ___
Persists
Bone marrow activity (production of new cells) ___ tolerance
Reduces
Immunosuppressive drugs ___ tolerance
Prolong
In general, ___ drive immune response and ___ turn it off
Antigens, antibodies
Antibodies have a feedback loop on B cells to inhibit
Further production of antibodies
____ antibodies inhibit antibody production in newborn
Maternal antibodies (clinical relevant for timing vaccines)
