Block 2 Lecture 1 -- Tolerance Flashcards
What is immunologic tolerance by definition?
unresponsiveness to an antigen
What characteristics stimulate in immunogenic response?
1) short-lived Ag
2) SubQ or ID
3) presence of adjuvants
4) stimulation of costimulatory molecules on APCs
What characteristics stimulate a tolerogenic immune response?
1) prolonged Ag
2) IV, mucosal, or generative presences
3) no adjuvants
4) low level costimulator and cytokine expression
Where does central tolerance occur?
thymus and bone marrow
What happens to the adult thymus over time in terms of anatomy?
1) cortex/medullary areas become smaller
2) perivascular space increases
3) incorporation of adipose
What is the result of thymic atrophy?
decreased T cell eduction and lower effector T cell output
– more infection and self-reactive T cells
Where does peripheral tolerance occur?
outside of primary lymphoid organs
What are the mechanisms of peripheral tolerance for T cells?
1) anergy
2) suppression
3) deletion
Define anergy.
lack of response to an antigen
What causes T-cell anergy?
1) lack of costimulation
- - no B7 to interact with CD28 resulting in signaling blockade
2) lack of innate immunity
- - no cyotkines to express co-stimulatory molecules
How do Tregs block T activation?
1) CTLA4 binds B7 of APC
2) secrete IL-10 and TGF-beta
3) bind/take-up IL-2
What is the function of IL-2
proinflammatory, activates T cells
How is peripheral T cell deletion/apoptosis accomplished?
1) hi-affinity deletion (same as central tolerance)
2) FasL/Fas
How does FasL-mediated deletion occur?
FasL (T-cell) binds to Fas (tumor/infected cell)
– hi-frequency CD8-killers upregulate Fas and themselves become killed
How do cancer cells take advantage of Fas/FasL?
upregulate FasL to kill hi-frequency-killing CTLs
