T Cell Tolerance (Exam 3) Flashcards
Term for unresponsiveness to antigen induced by previous exposure to that antigen.
tolerance
________ is an antigen that results in tolerance while _______ is an antigen that results in immunity.
tolerogen
immunogen
How can the same antigen be both tolerogenic and immunogenic?
dependent on how naive cell first encounters antigen
When a lymphocyte recognizes _______, it leads to proliferation and differentiation. When a lymphocyte recognizes _______, it leads to anergy or deletion.
microbes
self-antigen
________ is the first layer of removing self-reactive naive lymphocytes before entering circulation. ________ rids of mature T cells in the periphery that have escaped previous answer.
central tolerance
periphery tolerance
Where does central tolerance occur? Peripheral tolerance?
central: primary lymphoid organs
peripheral: generative organs
In central tolerance, if naive T cells are self-reactive, what are the possible outcomes?
- negative selection –> anergy or deletion
- made into regulatory T cells
What is the function of regulatory T cells?
leave thymus and inhibit self-reactive responses in periphery
What 3 fates can occur with self-reactive T cells in peripheral tolerance?
- anergy
- suppression (activation blocked by regulatory T cells)
- deletion (apoptosis)
When self-reactive T cells receive an inactivating signal and become functionally unresponsive it is called ________.
anergy
What are the two inhibitory receptors which inhibit T cell responses?
CTLA-4
PD-1
What 2 mechanisms does CTLA-4 use to inhibit T cell response?
- signaling block
- reduce B7 availability
How is a T cell response inhibited by CTLA-4 acting as a signaling block?
CTLA-4 activates B7 phosphatase –> phosphate removed from TCR = T cell response inhibited
How does CTLA-4 inhibit T cell response by reducing B7 availability?
binds to B7 on APCs so CD28 on T cells cannot bind it
______ is upregulated on T cells after chronic exposure to antigen.
PD-1
AIRE protein stands for __________.
autoimmune regulator
What is the function of AIRE protein?
part of central tolerance so self-proteins from tissues can be brought to thymus to test T cell self-reactiveness
(T/F) AIRE is a transcription factor expressed by thymic medullary epithelial cells.
True
What transcription factor is critical for development and function of T cells?
FoxP3
Function of FoxP3
transcription factor which can inhibit T cell responses
FoxP3 requires _____ and ____ cytokines which induce regulatory T cell development and FoxP3 expression.
TGF-B
IL-2
______ is a death receptor on T cells which is upregulated with repeated antigen stimulation. ______ is a ligand of the receptor.
Fas
FasL
What is the “signal for death”?
Fas ligand
How do Fas receptor and Fas ligand lead to cell death?
proteins assemble and cleave caspase-8 –> cleavage of other caspases = apoptosis
“Death by neglect” when activated T cells don’t get the signal to survive which leads to apoptosis is considered __________ cell death.
passive cell death
When activated T cells receive too much stimulation, they undergo apoptosis which is called ________ cell death.
activation-induced cell death
Passive cell death is ______ mediated while activation-induced cell death is ______ mediated.
Bim-mediated
Fas-mediated
What activates Bim in passive cell death? How does it cause apoptosis?
-activated by lack of costimulatory molecule
-activated Bim –> mitochondria cytochrome C + caspase-9 activated = apoptosis
