Surgery 2
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Describe the interaction btw cells with MHC and T-cell receptors | Interact with T cells and stimulate them to either coordinate immune response (CD4 T cell) or directly attack microbes/ infected cell/ tumor cell (CD8 T cell)
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MHC Class I: | on surface of all nucleated cells (interact with CD8)
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MHC Class II: | on surface of APCs (interact with CD4)
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Direct Pathway | T-cells and their receptors identify foreign MHC molecules on donor cells. This stimulates CD8 T Cells to attack an organ and cause rejection
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Indirect Pathway | CD4 T cells recognize foreign proteins after presentation by APC’s (APC’s pick up peptides shed from transplanted organs)
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Key component on T cell: | TCR = Cell surface protein
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Cytokine responsible for the majority of immune cell activation | IL-2
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Differences in survival between the various solid organs | Kidney: 85%; Kidney/Pancreas: 85%; Liver: 74%; Heart: 72%; Lung: 47%; Intestine: 47%
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Panel Reactive Antibodies (PRA): | Recipient’s blood is tested for Abs that react vs panel of foreign cells; higher % indicates presence of more Abs, greater chance for rejection
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Tolerance: | state of immune acceptance without immunosuppression; the overall goal of TP (rarely achieved)
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Hyperacute rejection | immediate destruction (as soon as blood flows through vessels) of a transplanted organ
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Acute Rejection | Rejection of transplanted organ that most often occurs between 5-90 days after receiving a TP (caused by T-cells).
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Chronic Rejection | graft vasculopathy
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Induction Immunosuppression | Antilymphocyte Abs used to prevent rejection until maintenance suppression is therapeutic
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Induction Immunosuppression: given when: | Given before or at time of TP
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Mainstay of LT immunosuppression tx: | steroid tx (prednisone)
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OKT3 MOA | Directed against CD3 antigen on T cells, TCR is removed from lymphocyte surface membrane, lymph cannot fn
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Zenapax & Simulect MOA | Antibodies directed against IL-2 receptor
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Inhibit DNA synthesis in quickly dividing cells | antimetabolites
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Cyclosporine / Tacrolimus MOA | Binds to calcineurin / impairs intracellular cascades which results in the decreased expression of IL-2 and the IL-2 receptor
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Sirolimus MOA | prevents T cells from entering the cell cycle
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Renal TP: 3 things to be sewn in: | renal a., renal v., ureter
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Used to assess renal TP post-op | US
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Renal TP complications | ATN; lymphoceles; renal a/v thrombosis; urine leak
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Why prefer the left kidney? | left renal vein is longer
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TP: CI include: | lack of psychosocial support
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Liver TP: candidate only if demonstrate: | low risk for EtOH relapse
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Liver TP: 5-yr survival: | 85%
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Liver TP: complications | Primary non-function of graft; vanishing bile duct syndrome; Biliary Leak; Thrombosis of hepatic artery
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Primary indication for panc TP | T1DM (not T2DM)
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Genl indication for TP | end stage dz of the organ being transplanted
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Heart TP: survival (1 & 5 yrs) | 1 year survival is 80%, 5 year survival is 70%
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Heart TP complications: | right heart dysfunction, brady arrhythmias
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Heart TP: Tachycardia is associated with: | acute rejection
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Lung TP: indicated for lung dz w/ life expectancy of: | < 2 years
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Lung TP survival (1 & 5 yr) | 1 yr survival is 70%, 5 yr survival is 50%
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Lung TP complications | infxn (pneumonia); chronic rejection
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