T Cell tolerance Flashcards
What is tolerance and where can it occur?
- lack of responsiveness to self
- occurs in thymus (central tolerance) and in the tissues (peripheral tolerance)
What is a tolerogenic antigen?
-one that a T cell binds and drives it towards unresponsiveness (anergy) or even death
3 general outcomes of T cell encounters with antigens
- activation
- tolerance
- ignorance
Usually placing skin graft from breed Y into Z is rejected, but what if the Z recipient was newborn?
-it would accept it because the IS is still developing and learning what is self and nonself
Negative selection occurs in the thymus to eliminate overactive T cells, but what about antigens that never make their way into the thymus? What process accounts for this and what are the 3 different categories of it?
- peripheral tolerance
1. lack of co-stimulation
2. regulatory (suppressive) T cells
3. Activation-induced cell death
What happens if a resting APC binds with peptide to a T cell?
-tolerogenic response because resting APC won’t have B7 that is needed to activate a naive T cell
Explain how CTLA4 can be used to make transplants across major MHC differences succeed.
-soluble CTLA4 will bind all of the available B7 and thus block T cell activation and transplant rejection
2 actions of Tregs
- production of inhibitory cytokines that block T cell effector functions
- interfering directly in T cell activation
Compare immunogenic vs. tolerogenic antigens on their presence in generative organs, presentation with second signals, and persistance
- T:present in generative organs for central tolerance; not presented with second signals (anergy or apoptosis); long-lived
- I: not in generative organs (peripheral); present with second signal to promote lymphocyte survival and activation; usually short lived
T/F: Central tolerance typically results in anergic T cells.
- false; results in clonal deletion
- remember, negative selection occurs in thymus which ends in apoptosis!!!
Why does it make sense that tolerogenic antigens are NOT presented with co-stimulatory signals?
-tolerance is the end result of only receiving signal 1!!! if you received both signals, you would activate a T cell population against that antigen which is the opposite of tolerance
Define central tolerance and peripheral tolerance.
- central tolerance refers to elimination of self-reactive lymphocytes during their development; clonal deletion
- peripheral tolerance refers to suppression of immune responses by cells that, although self-reactive, have escaped deletion during development
Activation-induced cell death: what is it? what signals it?
- stimulated T cells are eliminated by apoptosis after immunogenic challenge has been met
- apoptosis occurs following engagement of a cell surface receptor (Fas/CD95) expressed on ACTIVATED T cells
- can also occur due to unbalanced pro and anti-apoptotic proteins
How does Fas signalling work?
- activated a protease cascade resulting in DNA fragmentation and cell death
- death receptor!!!
- when activated, T cells upregulate Fas and FasL and once challenge is met, these link together and induce apoptosis in eachother
Describe T cell levels before and after antigen exposure to naive T cell
-have more after the fact and these are due to creation of memory cells
