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50 Cards in this Set
- Front
- Back
What are the 2 types of transplants done?
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-HSCT (bone marrow)
-SOT (solid organ) |
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What are the 2 pathways of Tcell recognition for transplant rejection?
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1. Direct
2. Indirect |
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What is the direct pathway?
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The MHC molecules on APC's in the graft are recognized by the recipient's own Tcells and induce a cell-mediated reaction.
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What is the indirect pathway?
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APCs from the recipient present foreign peptides from the graft to the recipient's own Tcells which respond and react.
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What is acute humoral rejection?
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The development of antibodies to a graft
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What is hyperacute rejection caused by?
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Preformed antibodies to the graft
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Is hyperacute rejection very common or clinically significant? Why?
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No; because crossmatching is now done prior to transplant.
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What is the direct pathway of Tcell-mediated rejection associated with?
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Acute cellular rejection
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What is the indirect pathway of Tcell-mediated rejection associated with?
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Chronic cellular rejection
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What is the usual manifestation of acute humoral rejection? Why?
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Vasculitis - because the initial target of the antibodies is the graft vasculature.
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How do we describe the genetics of MHC?
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As polygenic and polymorphic
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What does polygenic mean?
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There are several MHC genes
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What does polymorphic mean?
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There are many alleles of each of the several genes!
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What are the odds of being a perfect HLA match with an unrelated person?
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1/5000
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Does being a perfect HLA match with a graft donor help much?
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No not a lot
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What is more important that being a complete HLA match?
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Crossmatching donor WBC's to the recipient's serum, to see if they are recognized as foreign and rejected.
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Why is crossmatching essential?
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To prevent hyperacute rejection and graft loss within hours.
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When the direct pathway of allorecognition occurs, what are the resulting effector mechanisms?
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-CD8 cell becomes a CTL which directly attacks the graft
-CD4 cell becomes a Th1 cell and stimulates inflammation |
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When the indirect pathway of allorecognition occurs, what are the resulting effector mechanisms?
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CD4 cells damage the graft by local delayed type hypersensitivity, but there is no direct lysis of the graft.
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What are the 3 forms of rejection?
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1. Hyperacute
2. Acute 3. Chronic |
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How soon does hyperacute rejection occur?
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Within minutes to hours after transplant
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What is the basis of hyperacute rejection?
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Preformed antibodies present in the recipient's circulation
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What is the main pathology of hyperacute rejection?
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Vascular thrombosis
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What is the timeframe for acute rejection?
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Days-months-years
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What is the main pathology of acute rejection?
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Interstitial inflammation and vasculitis
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How is acute rejection treated?
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With immunosuppressive medications
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What is the main pathology of chronic rejection? Timeframe?
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Vascular fibrosis
-occurs over months to years |
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What is the classic example of hyperacute graft rejection?
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ABO mismatch
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What is the principal cause of early graft failure?
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Acute rejection
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What is acute rejection mainly mediated by?
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Tcells reacting against alloantigens in the graft.
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What are 3 types of medications used to suppress immune reactions?
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-Cyclosporine/Tacrolimus
-Corticosteroids -Anti-CD3 monoclonal antibody |
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How do Cyclosporine and Tacrolimus work?
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By inhibiting calcineurin which blocks Tcell cytokine secretion
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How do the corticosteroids suppress the immune system?
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By inhibiting macrophage cytokine secretion to reduce inflammation
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How does Anti-CD3 monoclonal Ab work as an immunosuppressant?
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By binding CD3 and promoting phagocytosis and C'mediated lysis - depletes Tcells.
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What are the complications of taking immunosuppressants?
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-Increased susceptibility to infections
-Increase in certain malignancies |
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What does chronic graft rejection lead to?
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Loss of graft function
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What is the basic mechanism of chronic graft rejection?
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-Tcell secreted cytokines stimulating fibroblast proliferation and vascular smooth muscle proliferation in the graft
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What is the ultimate result of chronic graft rejection?
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Graft vessel occlusion
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What are 3 histologic findings in chronic kidney rejection?
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1. Graft arteriosclerosis
2. Tubular atrophy 3. Interstitial fibrosis |
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Why is the incidence of chronic rejection and graft arteriosclerosis rising?
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Because treatments for acute rejection have gotten much better.
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In what patients is GVHD mostly observed?
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HSCT recipients
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What is hematopoietic stem cell transplant usually given to treat?
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Hematologic malignancy
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What is the basis of GVHD?
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-DONOR Tcells mount immune response to RECIPIENT tissues
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Why is GVHD a reaction of donor against recipient?
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Because the recipient's own immune system has been depleted or even ablated.
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What are the 3 manifesting symptoms of GVHD?
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-Skin rashes
-Liver damage - increased bilirubinemia -Diarrhea |
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What is the skin reaction that is caused by GVHD called?
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Interface dermatitis
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What is the cause of the skin lesions in GVHD?
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Apoptosis of keratinocytes
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What are the causes of the increased bilirubin in GVHD?
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-Bile duct damage!!
also.. -Cholestasis -Lobular hepatitis |
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What is the cause of diarrhea in GVHD?
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Apoptotic bodies in crypts
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What are the microscopic findings in GVHD?
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-Skin keratinocytes are pink and pyknotic
-Apoptotic bodies on GI biopsy |