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
how come immunologic/tolerance status of an individual reflects the T-cell population?
even if B-tolerance is gone, individual is still tolerant because most Ag are T-dependent
Antigens that are sequestered in hidden spots that are only exposed with trauma
- lens protein of eye
- spermatozoal Ags
- cartilage Ags
(weak/strong) immunogens are rendered tolerant more easily
weak
injection of Ag in —– form often results in tolerance
soluble, monomeric form
(less likely to be taken up by APCs)
tolerance is easy to induce in newborns because…
low APC population
destroying/blocking functions of ———— cells can result in tolerance
APC
effect of metabolism of ag on tolerance
nonmetabolizable substances cannot be presented, and thus result in tolerance
how can Ab regulate the immune response?
- feedback inhibition; when Ag is bound by a lot of Ab, only the highest affinity Abs can bind to the remaining Ag
- FCR regulation
drugs/therapies used to suppress the immune system
- cytotoxic agents (methotrexate)
- corticosteroids
- immunosuppressants (FK506, cyclosporine, rapamycin)
- radiation
how do cytotoxic agents work?
kill rapidly dividing cells, including lymphs
how do immunosuppressants work?
prevent T-cell activation
how does radiation work?
affects hematopoietic system
at proper dose, lymphs may be restored in weeks
