Term
What are the different types of transplants? |
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Definition
- Orthotopic - in a normal location - Heterotopic - Different location - Autologous - graft comes from yourself - Syngeneic - graft comes from a genetically identical individual - Allogeneic - Different individuals of the same species - Xenogeneic - Different species **Last 2 need rejection drugs. |
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Term
Where does antigen recognition and T cell differentiation take place? |
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Definition
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Term
What is the function of B cells in humoral immunity |
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Definition
Recognition of an antigen and secretion of antibodies Antibodies then label for opsonization, activate complement, or attract NK cells. |
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Term
What are the 3 signals for T cell activation? |
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Definition
1) Antigen + MHC - CD4 binds to MHC, CD3 is a drug target 2) Adhesion molecules - B7 + CD28. CTLA4 will block. LFA1/ICAM are also for adhesion 3) Release of IL-2 |
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Term
What pathways for T cell activation have drug targets? |
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Definition
- IP3/Calcineurin pathway - NF-AT - NFkB signalling pathway **Both lead to formation of IL-2 |
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Term
What reactions are involved in rejection? |
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Definition
- Hyperacute - Humoral - antibodies - Acute cellular - Chronic |
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Term
How do glucocorticoids help prevent rejection of transplants? |
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Definition
Inhibition of the NFkB pathway by either upregulating the IkB inhibitor or preventing transcription directly on the DNA |
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Term
What drugs are immunophilin-binding agents and how do they work? |
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Definition
- Tacrolimus/Prograf - inhibits Calcineurin - Sirolimus/Rapamune - inhibits mTOR --> in IL-2 step. IL-2 cannot stimulate mTOR, a necessary step. - Cyclosporin/Sandimmune or Neoral - also inhibits calcineurin --> NF-AT |
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Term
What drugs are purine antagonists and how do they work for transplant rejection? |
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Definition
- Azathioprine/Imuran - Mycophenolate/Cellcept Inhibit the synthesis of purines and thus DNA and RNA |
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Term
What polyclonal antibodies are used for transplant rejection, and how do they work?a |
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Definition
- ATGAM - LFA1, CD3, CD4, CD2 - Thymglobulin - IL2-R, CD44, MHC, CD2, CD45 **Bind to MULTIPLE surface antigens, depleting lymphocytes and blocking replications. TCR NOT INVOLVED! |
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Term
What monoclonal antibodies are used for transplant rejection, and how do they work?a |
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Definition
- OKT3/Orthoclone - binds to CD3 during first step. T cells redistributed to bone marrow - Daclizumab/Zenapax - binds to IL-2 receptors. Humanized - Basiliximab/Simulect - binds to IL-2 receptors. Chimeric. Binds only to ALPHA subunit of ACTIVATED t-cells |
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Term
How does Alemtuzumab/Campath work for transplant rejection? |
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Definition
Binds to CD52 on B cells, Tcells neutralize B cells. |
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Term
What drug for transplantation has affinity for B7? |
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Definition
-Belatacept/Nulojix Soluble CTLA4 binds to B7, preventing 2nd signal |
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Term
How does Bortezomid/Velcade work for transplant rejection? |
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Definition
NOT an antibody!! Proteosome inhibitor - buildup of proteins induces apoptosis. Degrades ubiquinated proteins, preventing protein destruction |
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