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58 Cards in this Set
- Front
- Back
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Is there an advantage to having an identical MHC locus between donor and recipient?
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Yes, but it's very very small.
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What is the major difference between hyperacute and first-set graft rejection?
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First-set can be treated, hyperacute cannot.
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How do we avoid hyperacute rejection?
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1. Absolute match of ABO locus
2. No recipient antibodies to cell-surface antigens of donor white cells |
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How long for first-set rejection symptoms to appear?
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7-15 days after transplantation
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General characteristic of first set rejection?
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CD8 infiltration and general inflammation
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Common immunosuppressive drugs used to treat first-set?
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Azathioprine, Prednisone, Cyclosporin A, Tacrolimus
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Christopher's creatinine?
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Very very elevated, suggesting imminent renal failure/kidney damage.
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Supportive treatment in cases of near-imminent renal failure/kidney insufficiency?
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Hemodialysis.
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Immunosuppressive treatment for lymphocyte infiltration into a transplant?
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Among other things, CD3+ antibodies
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What kind of disease is type I diabetes?
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A T-cell mediated autoimmune disorder in which lymphocytes get into the pancreas and kill beta cells.
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HLA genotypes expressed in diabetic patients?
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DR3 or DR4.
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HLA genotype that confers protection against IDDM?
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DR2, which will not be detected in a majority of diabetic patients?
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Is IDDM transferrable?
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In theory, yes. So it should also be stoppable by wiping out the resident T cell population.
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Long term sequelae of IDDM?
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Diabetic glomerulosclerosis.
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How does Cyclosporin A work?
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Suppressing the dephosphorylation activity of NFAT, in turn suppressing cytokine (IL-2) production.
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Define second-set rejection?
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After mounting an immune response to a donor kidney, for example, there are memory cells against that donor. Insert another organ with identical HLA-markers and the body will kill it much quicker.
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Problems with genetic determinism.
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It is not accurate to say: "Because a patient expresses alleles common to other patients with that disease, the alleles definitively cause the disease." Because the disease cause may be nearby or unknown but commonly transferred with the alleles. So, tough.
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Is the protective effect of HLA-DR2 allelles dominant or recessive to the susceptibility effects of HLA-DR3/DR4?
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Dominant. Weirdly. We don't know why.
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What's the relationship of infection to IDDM?
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In mice, higher rates of infection actually appear to offset development of IDDM.
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Why was vaccinia inoculation relatively successful against variola?
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Antigenic similarity between the two virii
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What is a killed vaccine?
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A virus whose ability to replicate (nucleic acid) has been destroyed
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What is an attenuated vaccine?
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A virus whose ability to replicate has been lessened, or its pathogenicity has been diminished.
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Why does the subunit vaccine for hepatitis B fail in 15% of the population?
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Those people do not have the capacity to present the antigen on their MHC II
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Examples of live-attenuated bacterial vaccines?
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BCG, salmonella typhi
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Define a conjugate vaccine
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The coupling of a polysaccharide, for example, to a T-cell dependent antigen
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Freund's complete adjuvant
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An emulsion of killed mycobacteria and mineral oil filled with antigens
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2 human approved adjuvant
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Alum
MF59: squalene, oil, and water |
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What would be the ideal method of inoculation with vaccines?
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Oral or nasal mucosa
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What is the risk of a live vaccine?
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Back mutation to pathogenicity
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Which polio vaccine is commonly used in the US?
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IVP, which is killed
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ISCOMS can stimulate what?
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CD 8 via presentation on MHC I complexes
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Why aren't there vaccines against chronic infections?
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Chronic infectious diseases usually misdirect or subvert the immune system, so its not good enough to stimulate the system with the disease in an attenuated form.
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How does recombinant attentuation work?
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If a virus contains genes specific for virulence and no other factors, those genes coul be severely mutated or deleted, leading to intact but innocuous vaccines.
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What was the result of the trial-gp120 HIV vaccine
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Total failure.
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Has anyone ever successfully cleared an HIV infection?
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No.
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What's the remaining problem with transplantation?
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The immunosuppression of the host reaction to the grafted tissue is systemic, not specific . . . and therefore carries a host of related problems
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The most important trigger of an immune response by the host to a transplant?
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HLA majorhistocompatability complex.
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Immunogenetics
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A subfield of immunology devoted to alloantigenics
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Are HLA distinctions important in blood transfusions?
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No, because erthyrocytes do not express MHC. But they do express A, B, O.
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The hemolytic reaction caused by a blood antigen mismatch in transfusion is analagous to . . .
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Type II hypersensitivity rxns
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Hyperacute graft rejection is analagous to . . .
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Type III hypersensitivity rxns. Complement is fixed to immune complexes throughout the graft
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Can HLA class I differences on a graft cause hyperacute rejections?
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Yes, if the recipient has antibodies to that polymorphism. To a lesser extent, so do class II
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What is the source of antibodies to different HLA allotypes?
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Pregnancy, previous transfusions, previous transplants.
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How is a recipient's transplant viability to potential donors tested?
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Their sera is tested against a panel of individuas and the positive reactions are expressed as a percentage of Panel Reactive Antibody
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The high a PRA . . .
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. . . the less likely a patient is to be matched to a viable donor.
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Problematic procedures that "inflame" the immune response of a patient before transplant
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1. Dialysis
2. Use of ischemic, cadaveric donors |
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First-set or acute rejection
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Occurs via host effect T cells slowly mounting a normal immune response against different HLA allotypes on the transplant
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How is acute rejection prevented?
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Immunosuppression
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Acute rejection is analagous to . . .
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a Type IV hypersensitivity rxn
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Direct pathway of allorecognition
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When recipient T cells are directly contacted by donor dendritic cells carrying donor HLA molecules and antigens
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Indirect pathway of allorecognition
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The donor dendritic cells move to the recipient lymph tissues and die. They are endocytosed by recipient dendritic cells and then their peptides are presented to CD4 cells via MHC II. There is an immune response, but it is less than the direct
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Chronic rejection
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Antibodies to the HLA I molecules of the graft are continuously stimulated, and react in the vasculature of the graft. The continual damage causes ischemia, and organ death.
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How is chronic rejection avoided?
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Unsuccessfully. Even minimizing the chances that a recipient will have memory B cells (antibodies) to the donor HLA I, the indirect pathway will still generate a new antibody response.
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The transfusion effect
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The rare occurence that a recipient will have a blood transfusion with HLAs similar to the later transplant, and will therefore autoregulate the immune rejection after transplantation. Kind of cool.
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What three HLA types are most critical for a successful transplant match?
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HLA-A, HLA-B, HLA-DR
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3 kinds of immunosuppressive drugs
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1. Corticosteroids: anti-inflammatory
2. Cytotoxic: kill proliferation and interfere with DNA 3. Microbial products: interfere with T-cell signaling |
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The incidence of cancer in immunosuppressed transplant patients?
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3 times that of their peer
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Prednisone
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A synthetic derivative of hydrocortisone, 4 times more effective.
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