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9 Cards in this Set
- Front
- Back
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What are the 5 general principles of organ transplant therapy?
What cells primarily mediate graft rejection? |
1. ABO & HLA match
2. Multi-drug immune suppression - diff drugs w/ diff toxicities - lower doses of each possible i/combo 3. immunosupp. needs to be more robust early on 4. pts are monitored for transplant rejection using various assays. 5. if drug toxicity is detected, then the therapy should be stopped/modified. T-cells |
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What does formation of the TCR/CD3/antigen/MHC complex result in?
What does this molecule do? What does IL-2 do? (2) |
calcineurin activation in the T-cell cytoplasm.
dephos transcription factor NF-AT --> enters nucleus --> ramps up IL-2 production.` - stim clonal expansion of T-cells & other immune cells - sim 'target of rapamycin' (TOR) which regulates mRNA translation. |
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What are the three (general) different regimens for employing immunosuppressant drugs?
Drug classes involved? |
induction:
- steroids - antibodies to IL-2 maintenance - calcineurin inhib - steroids - antimetabolite rescue/rejection - steroids |
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Daclizumab, Basiliximab
- what are they? |
- monoclonal antibodies targeted against IL-2 receptor on the surface of activated T-cells
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What are the two calcineurin inhibitors commonly used?
- mech? - side effects? Antimetabolites in Maintenance therapy? (2) - how do they work? - side effects? |
Tacrolimus, cyclosporin
- b/ immunophilins and then inhib calcineurin - impaired kidney function mycophenolate - compet inhib enzyme that lymphocytes require for DNA synth that other cells don't need azathiprine - incorporated into DNA, inhibiting it's proper function. There are some signif side effects, but they're less problematic than the steroids and calcineurin inhibitors. |
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Why are TOR inhibitors being actively sought?
What are two examples? - mech? |
the calcineurin inhibitors are pretty nephrotoxic and steroids are a pain in the ass.
sirolimus, everolimus - b/ FKBP-12 just like tacrolimus, but they inhibit TOR not calcineurin. --> blocks G1->S, and suppressess growth of smooth muscle and endothelial cells --> \graft atherosclerosis. |
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What are the four principal categories of rejection?
Characterize them. |
hyperacute, acute cellular, acute humoral, chronic.
hyperacute: - preformed antibodies - v.fast (ABO, HLA, endothelial) acute cellular: - T-cell mediated - 3-6 months post-txp - lesions at txp site filled w/ macroP and lymphocytes acute humoral: - antibodies - days to weeks post-txp chronic: - unclear mechanism |
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Define rejection rescue therapy (and the preferred agents (3))
What is cytokine release syndrome? |
tx w/ antilymphocytic antibodies to reduce their lvls.
**Thymoglobulin causes complement dependent oposonization and lysis of lymphocytes OKT3 (muromonab-CD3) --> renders the T-cells unable to respond to an antigen challenge. - intial binding results in activation of the T-cell --> cytokine release syndrome ATGAM; works similiarly to thymoglobulin. |
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The four types of rejection are hyperacute, acute cellular, acute humoral, and chronic. How are they tx'ed?
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Acute Cellular
- IV methylprednisolone or rescue therapy Acute humoral: - IV methylprednisolone w/ oral prednisone. - Plasmapheresis - consider rituximab if all else fails; capable of killing B-cells. Chronic (aka CAV): - angioplasty if there is focal ischemia - TOR inhibitors have been found to reduce/reverse CAV |
