tolerance, autoimmunity, and transplantation Flashcards
T cells are activated when ____ interacts with ___
MHC and antigen
for a naive T cell to be activated, you need 2 signals:
2 signal model
1) TCR + CD3
2) costimulation of CD28 (on the Tcell) + B7 costimulatory molecule (on the antigen presenting cell)
**must be a professional antigen presenting cell!
4 mechanisms that contribute to immunological self tolerance
1) negative selection of self reactive B cells in the bone marrow
2) central thymic tolerance = positive + negative selection
3) exclusion of lymphocytes from certain tissues (eyes, brain, testis)
4) peripheral tolerance of self antigens (for the self reactive T cells that escape the thymus)
central tolerance
thymus expresses tissue specific proteins that
1) select for TCR with affinity to MHC (others die)
2) negative selection of cells with high reactivity against self
end up with Tcells with MHC affinity without high self-reactivity
lymphocytes are excluded from what tissues
eyes brain and testis (immunologically priivileged = no T cells allowed)
peripheral tolerance to self-antigens
since some T cells with reactivity against self do get out of the thymus, there are two peripheral ways to prevent autoreactions
1) anergy = permanently inactivates auto-reactive T cells by preventing 2nd costimulatory signals (only signal 1 occurs)
2) suppression of autoimmune responses by Tregs (regulatory T cells)
Tregs suppress the activation of all the other self reactive CD4 T cells using
–TGFbeta
–IL-10
and
–direct cell-cell contact by reacting with the same APC (antigen presenting cell)
development of autoimmune disease
3 mechanisms
• Failure or reversal in T cell tolerance = auto reactive T cells must be present in the development of autoimmune disease
- release of antigens that are normally sequestered
- failure of central tolerance
- failure of peripheral tolerance (failed anergy or Tregs)
autoimmunity due to eye trauma
eye specific proteins are released into periphery, resulting in T cell activation and immune response against both eyes
(t cells normally cant get into the eye -havent been exposed to eye specific antigen before)
causes immune mediated blindness in BOTH eyes
AIRE mutation
= APECED (autoimmune polyendocrinopathy)
defective negative selection of self-reactive T cells
group A strep infection is associated with what autoimmune condition?
rheumatic fever (carditis and polyarthritis)
d/t molecular mimicry
o Regardless of the trigger, a major mechanism underlying most autoimmune diseases is …
activation of T cells by self-antigen presented by specific MHC alleles
they are basically type 2,3, or 4 hypersensitivity reactions directed against self-antigens
hypersensitivity type 1
name?
associated diseases?
mediator?
immediate
atopy, anaphylaxis, and asthma
IgE
hypersensitivity type 2
name?
associated diseases?
mediator?
antibody mediated
hemolytic anemia, goodpastures, and erythroblastosis fetalis
IgG or IgM and complement
hypersensitivity type 3
name?
associated diseases?
mediator?
immune complex-mediated
serum sickness, arthus reaction, lupus nephritis
IgG and complement
