Term
| Understand the immunological basis for graft rejection following tissue transplantation |
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Definition
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Term
| Describe the different mechanisms that promote graft rejection |
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Definition
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Term
| Understand the principles of immunosuppressive therapy and the associated risks |
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Definition
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Term
| Identify risk factors that can negatively impact successful tissue transplantation |
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Definition
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Term
| is the graft accepted or rejected in a transplant between non-identical siblings? |
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Definition
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Term
| differences in which genes are the major cause of transplant rejection? |
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Definition
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Term
| is blood considered a tissue transplant? |
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Definition
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Term
| since RBCs dont express MHCs on their surface, why do we worry about them? |
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Definition
| because they express other antigens (ABO, Rh+/-) |
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Term
| How do MHC allelic differences promote such strong immune responses? |
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Definition
| Typical response to transplant: 1/3 T cells. Compared to typical response to a pathogen at <1/10,000. |
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Term
| do you get a stronger reaction with more HLA differences? Why or why not? |
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Definition
| Yes, its stronger in proportion with # of allelic differences between recipient and donor. |
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Term
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Definition
| “Same” = HLA match at all alleles |
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Term
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Definition
| Same species = HLA mismatch (alloantigens) |
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Term
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Definition
| Same species = HLA mismatch (alloantigens) |
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Term
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Definition
| Different species = HLA mismatch (xenoantigens) |
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Term
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Definition
| Human Leukocyte Antigens. The major antigen compatibility complex in humans that is genetically determined and is involved in cell self-identification and histocompatibility. |
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Term
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Definition
| essentially Cross-reactivity of the T cell receptor on the MHC molecules. |
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Term
| Why is the T cell response to alloantigens so large? Two factors: |
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Definition
| 1) T cells that respond strongly to allogeneic MHC molecules were not deleted during T cell development. 2) All allogeneic MHC molecules on the cell surface of the transplant represent targets for the T cells. |
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Term
| Can dendritic cells from a donor present allogeneic MHC molecules to recipient's T cells? |
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Definition
| yes. it works to activate the T cells. Called Direct Recognition |
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Term
| what is Indirect Recognition? |
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Definition
| when a recipient's Dendritic cells pick up and present the donor's allogeneic MHC molecule to a T cell. |
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Term
| Do B cells respond to the allogeneic MHCs? |
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Definition
| yes, when they presented by dendritic cells they will release antibodies to bind to cells in the graft |
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Term
| what are 3 mechanisms of Graft rejection? |
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Definition
| 1) Hyperacute, 2) Acute, 3) Chronic |
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Term
| When does Hyperacute graft rejection occur? |
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Definition
| most commonly with blood transfusion. Responds to alloantigens due to previous transfusions, pregnancy or transplants. |
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Term
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Definition
| an antigen present in allelic forms encoded at the same gene locus in different individuals of the same species. |
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Term
| how and why can a pregnant mother develop alloreactive antibodies during birth? |
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Definition
| During the trauma of birth, fetal cells enter the mothers blood stream, exposing her to the paternally-derived HLA antigens of the baby. |
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Term
| What takes place in Acute graft rejection? |
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Definition
| T cells activated and build up in #s, then destroys the donor's tissue. Immunosuppressive drugs are used to block T cell activation. |
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Term
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Definition
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Term
| what takes place in a chronic graft rejection? |
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Definition
| likely due to indirect recognition of alloantigen (the allogeneic MHCs) by T cells. The T cells activating lead to a cytokine production which promotes proliferation of fibroblasts and vascular smooth muscle cells --> cutting off blood supply |
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Term
| what do these drugs do?: Cyclosporine A and FK506 (tacrolimus) |
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Definition
| Bind calcineurin, inhibiting activation of NFAT |
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Term
| which drug inhibits IL-2 signaling, blocking T cell proliferation? |
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Definition
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Term
| what do corticosteroids do to promote graft acceptance? |
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Definition
| Decrease cytokine production by macrohages |
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Term
| how does Anti-CD3 work to promote graft acceptance? |
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Definition
| T cell depletion through phagocytosis |
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Term
| the drug, CTLA4-Ig, blocks binding of _____ to CD28 to inhibit T cell activation. |
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Definition
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Term
| what is Xenotransplantation? |
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Definition
| tissues come from animals (like pigs) |
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Term
| what disorders can you treat with Hematopoietic Stem Cell Transplantation? |
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Definition
| many genetic disorders in which blood cells or cells of the immune system are defective. Cancers including leukemias, multiple myeloma, non-Hodgkin’s lymphoma and some solid tumors. |
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Term
| how does Hematopoietic Stem Cell Transplantation work? |
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Definition
| 1)Donor hematopoietic stem cells seed the host’s bone marrow. 2) Immune cells of donor origin reconstitute the bone marrow and lymphoid organs. 3) T cell precursors of donor origin learn to recognize antigen on both host (parenchymal cells) and donor (Dendritic cells) MHC molecules in the thymus. 4) This promotes T cell tolerance to host HLA molecules. 5) The closer the HLA match, the better this chimeric immune system will work. |
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Term
| what is Graft Versus Host Disease (GVHD)? |
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Definition
| T cells present in the donor bone marrow can respond to host APCs expressing alloantigens, leading to activation and then recognition of host parenchymal cells |
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Term
| The MHC is the main roadblock to successful tissue transplantation |
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Definition
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Term
| The closer the HLA match, the more likely the long-term success of the transplant |
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Definition
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Term
| Current immunosuppression approaches are not alloantigen-specific and increase the risk for infections and cancer development |
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Definition
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