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16 Cards in this Set
- Front
- Back
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Blood and Lymph- Transplantation Immunology by Jackson
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Blood and Lymph- Transplantation Immunology by Jackson
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Highlighted Objective:
role of HLA molecules in graft recognition and rejection |
generally, the the MHC (HLA) presents to T-cells. Peptides on them are recognized by T-cells to kick off the immune response.
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Highlighted Objective:
methods for preventing graft rejection |
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Highlighted Objective:
availability of donor organs |
big problem. there's a shortage of organs for transplantation.
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Why does rejection occur? What is it due to?
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Rejection occurs due to immune recognition and response to foreign histocompatibility antigens
MHC are most important antigens of rejection Activated T-helper cells are important Cytokines increase graft HLA and CAM Graft rejection reduced by matching HLA types Non-specific immunosuppressive agents used *MHC is the most important, but there can still be a rejection if the other histocompatability antigens don't match |
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Describe Class I HLA antigens. Where are they found?
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Class I. There are three different class I antigens...HLA-A,B and C are on chromosome 6.
These genes are polymorphic (variants in the human population) and each variants are an allele of each other. Class I is found on all nucleated cells. The MHC Class I molecule is on the surface of the cell, and has a peptide binding groove and a B2 microglobulin for structural stability. |
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What about Class II?
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There is HLA-DR, DQ, DP, and an alpha and beta for each.
They encode 2 separate proteins (alpha and beta, as opposed to class I which only encode 1) Class II are found on Antigen Presenting Cells (macrophages, dendritic cells, B cells) |
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How many different HLA molecules are on the B cell surface?
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All of them. Different types of peptides...gives the immune response a better chance of having a peptide displayed for the immune response to see (recognize infection). All the HLA genes are conominantly expressed on the cell surface (multiple copies of each one).
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Haplotype. How many does each person get?
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One complete set of these genes on a chromosome. Each individual will receive two complete MHC haplotypes
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Hyperacute, Acute, and Chronic Rejection... how long for each, what is the mechanism?
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Hyperacute- minutes to hours; preformed anti-donor Ab and complement
Acute- days to weeks; cell-mediated or humoral Chronic- months to years; unclear mechanism |
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An example of a hyperacute rejection is
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kidney transplant when the donor and recipient are not matched for the ABO antigens. Type A has naturally anti-B antibodies in the serum (mostly IgM, which fix complement well)
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What is an example of an acute rejection?
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cyclosporin and steroids. Primary recognition by T-cells of the foreign MHC molecules or minor histocompatability antigens if they still match for HLA. This triggers rejection by inflammatory cytokines involving complement and antibody activation, detected by C4d.
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What do immunosuppresive drugs try to suppress?
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T-cell activation and proliferation. T-cells is at the heart of recognition and acute rejection.
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How do we get more organs for transplantation? Is the pig the answer?
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humans create a natural antibody that reacts against a glycoprotein on pig cells. so there will be an acute or hyperacute rejection.
another answer is living donors. better than cadavers. |
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Hematopoietic Cell Transplantation (HCT)
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-Used to treat malignancy, immunodeficiency, bone marrow defects, autoimmunity
-GVHD problem -Stem cells obtained from bone marrow, peripheral blood, and cord blood -CD34 marker -Mobilization of CD34+ cells (marker for early hematopoetic stem cell) |
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Acute vs Chronic Graft-versus-Host Disease
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Acute GVHD
Maculopapular rash, scaling Diarrhea, hepatosplenomegaly, jaundice Cardiac irregularity, CNS irritability, pulmonary infiltrates Chronic GVHD Chronic skin desquamation Hepatosplenomegaly, lymphadenopathy Chronic diarrhea and failure to thrive Severe immunodeficiency *there are still mature T-cells in the bone marrow, peripheral blood, cord blood, which recognize the foreign MHC in the recipient and start a reaction. *try to eliminate mature T-cells from the graft as much as possible. |
