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17 Cards in this Set
- Front
- Back
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What is an autograft?
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A structure from the same individual that is inserted back in, like a parathyroid gland.
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What is a xenograft?
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A tissue transplant between members of the same species (not identical twins), known as allogeneic.
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What molecule is the greatest barrier to successful organ transplantation?
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MHC because foreign organs will be pathogenic, causing the immune system to attack the graft.
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What is the direct mechanism of rejection?
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Heresy. Activation of the immune system by the foreign MHC itself, without any MHC processing or presentation.
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What is the indirect mechanism of rejection?
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Standard processing of alloantigens and presentation by MHC II molecules. Cross-priming will also activate the CD8 response.
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Describe the sequence of classic, indirect mechanism of transplant rejection.
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1) CD4 T-cells are mandatory participants.
2) Cross-priming may include CD8 T-cells also. 3) NK cells may participate, but are not mandatory. 4) Graft destruction by macrophages, CD8 cytotoxicity, and the complement/FcR activation pathway. |
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How is rejection defined clinically?
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By its temporal relationship to the actual transplant.
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What is hyperacute rejection?
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Near immediate rejection of the graft due to an antigen mismatch (RBC) present PRIOR to the transplant. An immediate complement response destroys the epithelial lining - DISASTER.
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What is acute rejection?
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Within the first 3 weeks of transplantation, the host immune response reacts to the alloantigens, causing a Th1 and Th2 response against the graft. Typically due to a degree of MHC D locus mismatch.
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What is chronic rejection?
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A slow rejection of the graft of unkown mechanism that results in arteriolar narrowing. This is irreversible.
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What are 4 strategies to prevent transplant rejection?
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1) Optimize the MHC matches, especially in the D loci.
2) Block the T-cell response by immunosuppression. 3) Suppress the Th1/CD8 response with IL-10 and TGF-beta, or CTLA-4. 4) Induce tolerance by manipulating CD4,25 T-reg cells. |
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What is Graft vs. Host (GvH) disease?
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The DONOR T-cells begin to attack the host, sensing foreign alloantigens. Unique to bone marrow transplants or any situation where the recipient is immunodeficient.
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What is the α-1,3-GT gene, and how is it significant in transplants?
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A gene that was deleted long ago in higher primates, and currently we produce huge amounts of anti-α-gal Ab's after being exposed to the epitope in GI bacteria. This makes pig xenografts difficult because immediate hyperacute rejection will ensue, due to the presence of this protein on all lower species.
Human DAF gene may be inserted into pigs to dull the hyperacute rejection, but even if successful, acute and chronic rejection still need to be dealt with. |
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What are the 5 maternal strategies for preventing fetal allogeneic rejection?
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1) Maternal NK cells display CD56-bright, which can't lyse cells marked with HLA-G (trophocytoblastic fetal tissue).
2) Maternal γδ T cells and CD4,25 T-reg cells can suppress activated maternal αβ T cells. 3) Placental trophoblastic tissue can induce FAS-mediated death of maternal T-cells that may attack fetal tissue. 4) Uterine cytokine milieu of IL-4,5,10 and TGF-β, and fetal contribution of IL-10 and TGF-β will create a bias to Th2 response. 5) Maternal progesterone and other placenta-derived factors will suppress Th- 1 response. |
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What is the primary strategy of the fetus to prevent its own rejection?
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Fetal tissues that come in contact with the maternal interface do not display classic HLA-A,B,C molecules because MHC is downregulated. Instead, HLA-G is displayed, which is an inhibitor of maternal NK cells.
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How might dominance of the INF-gamma cytokine affect pregnancy?
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This will create a Th1 bias, which will prevent successful implantation or fetal resorption, which is death of the fetus anytime after the 9th week of gestation.
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What kind of effects will pregnancy have on maternal illness?
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The maternal immune response is Th2 biased. Any illnesses requiring a heavy Th1 response will be exacerbated - TB, leprosy, influenza, etc.
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