Immunology 10 - Immunology 10- Major Histocompatability...

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Immunology 10- Major Histocompatability Complex System MHC is polygenic= contains several different MHC I and MHC II genes, so every individual possesses a set of MHC molecules with different ranges of peptide bonding specificities MHC is polymorphic= there are multiple alleles of each gene within the population as a whole Organ Transplantation Scientific understanding of immunological tolerance started with the field of clinical organ transplantation 1930’s/40’s: dogma of scientists was that human organ transplantation was impossible, because “the basis of individuality lay deep within every cell in the body” (Joseph E Murray) These beliefs were based on the pioneering work of Peter Medawar Sir Peter Medawar—Nobel Prize in Physiology If cells from on experimental animal are injected into a second, they will be recognized and destroyed by the immune system; the second time they are injected they will be recognized and destroyed more rapidly; immunological rejection; same occurs with skin grafts However, if cells from an experimental animal are injected into a newborn recipient, not only are they not destroyed, but for the rest of its life that animal will not recognize or destroy cells from the donor animal= immunological tolerance; has something to do with recipient not being developed Kidney Transplantation 1940’s: large number of young persons dying of terminal renal disease, whose only barrier to health was the fact that their kidneys were diseased; doctor’s started performing kidney transplants in the 40’s because the procedure had clinical benefit to the recipients Kidney grafts never lasted more than 3 months as a consequence of immunological rejection Organ Transplant 1954: Joseph Murray identified a patient with kidney failure who had an identical twin brother; realized that it should result in immunological tolerance to the transplanted kidney; patient survived long term; became the most famous transplant in history Also performed first successful long term allograft between fraternal twins, and first successful long-term cadaveric (deceased donor) transplant; nobel prize in 1990 Clinical procedures preceded any knowledge of the molecular basis of rejection The HLA Antigens Injection of blood cells from one individual to another caused an immune response to the injected cells, including generation of specific antibodies; without knowing what they were, the antigens were called human leukocyte antigens (HLA) ; cell surface proteins The Major Histocompatibility Complex Majority of genes encoding human leukocyte antigens were mapped to a region on chromosome 6 on humans and chromosome 17 in mice= major histocompatability complex (MHC); genes within this complex are called the human leukocyte antigen (HLA genes) in humans and the H-2 genes in mice MHC in both mice and humans extends over 4000000 base pairs of DNA and encodes over 200 genes; diverse Functions of the proteins are highly related
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Immunology 10 - Immunology 10- Major Histocompatability...

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