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21 Cards in this Set
- Front
- Back
Autograft, Isograft, Allograft, Xenograft
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Autograft- from same person
Isograft- from identical twin Allograft- w/i same species Xenograft- other species |
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Most important determinant for transplant rejection?
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HLA antigens that are recognized foreign by your T-cells. Once recognized as foreign, they make the cytokines, then you get a full blown immune response
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MHC-I found where? MHC-II found where?
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MHC-I found on all nucleated cells. A,B,C; encodes 1 protein
MHC-II found only on antigen presenting cells encodes 2 proteins (alpha and beta) Found on chromosome 6, and inherited as a whole block of genes *primary role in the immune response is to present antigen peptides to T-cells |
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Haplotype
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complete set of genes on one chromosome; we each have 2 complete HLA haplotypes which are codominantly expressed (all expressed)
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Hyperacute
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minutes to hours; preformed anti-donor antibodies and complement; may or may not recognize HLA differences.
example is ABO blood groups for donor and recipients |
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Acute
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Days to weeks; primary activation of T-cells and macrophages
T-cells in the recipient recognizing something foreign in the donors tissue, most likely HLA antigens |
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Chronic
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Months-years; unclear mechanism.
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Immunologic Rejection Mechanisms
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whats targeted in the grafted organ is the vasculature so organ dies.
APC from graft can enter recip. bloodstream, to the lymph, present MHC Ags to T-cells, stimulate activation. |
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How to prevent Graft rejection?
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1. Match donor and recipient for HLA
-via serological teissue typing -cross match (test for Abs against donor cells), coombs -genotyping 2. Immunosuppressive Drugs -cyclosporin |
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Cyclosporin and Tacrolimus
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Block T cell cytokine production
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Azathioprine
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blocks proliferation of lymphocyte precursors
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Mycophenolate Mofetil
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Blocks lymphocyte proliferation by inhibiting guanine nucleotide synthesis
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Rapamycin
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blocks lymphocyte proliferation by inhibiting IL-2 signaling
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Corticosteroids
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Reduce inflammation
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Anti-CD3 monoclonal Ab
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inhibit T cells
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Anti IL-2 receptor AB
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inihbits T cell proliferation
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CTLA-4-Ig
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inhibits T cell activation by blocking B7 co-stimulator binding to CD28
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Graft Versus Host Disease, where does it happen the most?
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HLA antigens aren't matched perfectly.
especially seen in BONE MARROW TRANSPLANTATION. The T-cells in the transplant attack the recipient's tissues. |
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prevent GVHD
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Removal of mature T cells from graft, immunosuppressive therapy, autologous transplantation, stem cell transplantation
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CD34
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used to purify hematopoetic stem cells. Found on early stem cells and can turn into many hematopoetic cells.
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Why is the fetus not rejected?
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-immunosuppression of the uterus
-Th2 dominant T-cell responses (th1 more likely to reject) -low level MHC class I expression (less cytotoxic t cell vulnerability) -High level of HLA-G expression on trophoblast (sends signals to turn off NK cells) |