11) Control mechanisms Flashcards
major aspects of immune response that need regulation
- development of pathways of immunocompetence
- response of mature lymphs to Ag
draw the tolerance kinetics graph
tolerance
state of unresponsiveness to an epitope
Ag-specific
tolerance occurs when interaction with Ag + lymph results in….
- inactivation
- deletion
- apoptosis
- become anergic
anergic lymph
unresponsive
only cells with ——– can be tolerized
Ag-specific receptors
(t/f) tolerance can only be achieved at certain stages of development
false; any stage
how are immature lymphs tolerized?
which cells are tolerized?
negative selection
T-cells —thymus, when cells express TCR, 𝛼β, CD4 and CD8
B-cells —in BM
result if immature T and B cells are exposed to foreign antigen
inactivation
(not normal)
causes of autoimmune disease in relation to lymph development
- self-reactive lymphs escape negative selection (just below critical affinity threshold)
- self-antigens hidden during development
- B-cell negative selection not as stringent as T-cell (not a problem because most Ag are T-dependent)
how can tolerance be induced in mature T-cells?
examples
presentation of Ag in incomplete or ineffective way
- B7-CD28 interaction missing
- Ag presented by pancreas, liver, kidney cells induced to express MHC II (no costimulatory signal)
anergized T-cells do not make…
IL-2
tolerance can reverse if induced by…
Ag presented by pancreas, liver, kidney cells induced to express MHC II (no costimulatory signal)
how can tolerance be induced in mature B-cells?
absence of T-cell signals
T-suppressors usually CD– +
4
possible mechanisms of T-suppressor action
- produce inhibitory cytokines (IFN-𝛾, TGF-β)
- CD8+ cells may have cytotoxic effects on other T-cells
general factors that ↑ tolerance
- fetus only response with IgM
- elderly, general decrease in immune function
- malnutrition
- Bare lymphocyte syndrome
how does malnutrition contribute to tolerance?
- ↓ T-cells
- impaired complement system
- impaired phagocytosis
no MHC expression on any cells
no T-cell response
B-cells produce only IgM
bare lymphocyte syndrome
doses of Ag that induce tolerance vs immunity
low and high doses: tolerance
intermediate doses: immunity
duration of tolerance is shorter in —– lymphs
B
(maintained 49 days, while T-cells live 100 days)
why do T-cells need to last longer than B-cells?
thymus atrophies with age
BM replaces B-cells more rapidly
reasons to induce tolerance
- prevent transplant rejection
- control autoimmune disorders
- control allergic diseases
- create drug therapies
when does tolerance occur in both lymph lines?
- T: within 24 hours of exposure
- B: within 10-11 days of exposure
