Immunosupressants Flashcards
(44 cards)
what are 3 applications of immunosuppressants?
- suppress rejection of donor organs/tissues
- suppress ‘Graft-vs-Host’ disease (GVHD)
- auto-immune diseases
what is the ‘Graft-vs-host’ disease?
donor lymphocytes (on graft) begin to attack host (opp rxn to transplant rejection: host->donor)
what causes the transplant rejection rxn?
antigens on donor organ are recognized as ‘non-self’ and host initiates immune response to attack it
what are 4 ex of autoimmune diseases?
rheumatoid arthritis, lupus, ulcerative colitis, psoriasis
t/f: cancer chemotherapeutic drugs and immunosuppressants are very different
false, there is great overlap btwn immunosuppressants and cancer chemotherapeutic drugs (stop rapidly dividing cells)
what are the 2 main phases of the adaptive immune response?
induction and effector
what are the 2 parts of the induction phase of the adaptive immune response?
antigen presentation and clonal expansion/maturation
what is the antigen presentation phase?
an antigen-presenting cell absorbs, processes, and expresses an antigen to a T-helper precursor cell which activates that clonal expansion and differentiation phase
what is the clonal expansion and maturation phase? (3)
T-helper precursor cells release IL-2 which has + feedback causing incr division and differentiation into T-helper 0 cells, Th0 cells secrete IL-4 (same + feedback as IL-2) and cause differentiation into Th1 and Th2 cells, Th1 cells become mature Th1 cells or cytotoxic t-cells and Th2 cells become B-cells (both by clonal expansion)
what is the effector phase? (3)
B-cells produce antibody-mediated response (Abs against Ags), T-cells produce cell-mediated response (Th1 cells secrete cytokines, cytotoxic t-cells kill infected cells)
what is the adaptive immune response aka?
specific immune response
what phase of the adaptive/specific immune response do most immunosuppressant drugs exhibit their effects?
induction phase
what 5 steps/mechanisms do immunosuppressant drugs target/utilize?
- inhibit IL-2 (+ feedback)
- inhibit cytokine gene expression (glucocorticoids)
- cytotoxicity (kill immune cells/prevent maturation/expansion)
- inhibit nucleic acid synthesis (rapid repl’n during clonal expansion)
- block t-cell surface receptors (Abs block Ag-presentation/immune response activation)
what does activation of Th0 cells require?
activation of calcineurin-NFAT (nuclear factor of activated t-cells) signalling pathway
what is that calcineurin-NFAT pathway?
t-cell receptor (interacts w/ APC) activation generates Ca signal (via PLC) that activates calcineurin (phosphatase) which dephosphorylates NFAT
what can dephosphorylated NFAT do? (3)
migrate to t-cell nucleus, act as a transcription factor and express IL-2 gene (for t-cell maturation/proliferation)
what are 2 ex of calcineurin inhibitors?
cyclosporine and tacrolimus
what are the targets of cyclosporine and tacrolimus resp.?
cyclophilin and FKBP
what do drug-bound cyclophilin and FKBP do?
suppress calcineurin, decr NFAT transcription of IL-2 and suppress t-cell maturation/proliferation
what do proliferation signal inhibitors do?
interfere w/ signals of IL-2 receptor activation
what is a major pathway responsible for cell growth and proliferation? (affected by proliferation signal inhibitors)
mTOR
what is an ex of a proliferation signal inhibitor?
rapamycin (aka sirolimus)
what is the target and effect of rapamycin/sirolimus?
FKBP (same as tacrolimus)
t/f: rapamycin/sirolimus has the same effects as tacrolimus when bound to FKBP
false, rapamycin-FKBP doesn’t inhibit calcineurin
