The Nobel Prize in Physiology or Medicine 1996
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Clinical Implications |
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There are many different variants of major
histocompatibility complex (MHC) molecules. We all
carry different combinations. Such variation is
caused by the MHC genes that we have inherited. Many
chronic inflammatory diseases have been shown to
occur preferentially in individuals carrying certain
variants of MHC genes.
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The understanding of how T lymphocytes recognize
antigens in association with a specific variant of an
MHC molecule has led to better understanding of how
the immune cells destroy brain tissue or joints in
"autoimmune diseases". This provides a basis to
specifically change or avoid reactions causing
autoimmune disease, while not disturbing immune
reactions against microorganisms.
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The understanding of how T lymphocytes recognize
antigens in association with a specific variant of an
MHC molecule has led to better understanding of how
the immune cells destroy brain tissue or joints in
"autoimmune diseases". This provides a basis to
specifically change or avoid reactions causing
autoimmune disease, while not disturbing immune
reactions against microorganisms.
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| Multiple sclerosis (MS) is an autoimmune disease in which destructive immune reactions occur within the brain, causing loss of the myelin sheath surrounding neurons. Such loss may cause paresis and affect both vision and psychic functions. Individuals with the DR2 variant of MHC genes are most susceptible to the disease. |  |
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| Rheumatoid arthritis (RA) affects peripheral joints and may cause destruction of both cartilage and bone. The disease affects mainly individuals carrying the DR4 variant of MHC genes. This feature can now be used both to make better prognoses and in aiding efforts to change immune reactions that involve the DR4 variant while leaving other reactions intact. |
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Towards Novel Vaccines. Vaccination is the most important way to make use of the immune system in medicine. By vaccination we prepare the immune system to respond earlier and more efficiently against the antigen in question. The discovery of Doherty and Zinkernagel has taught us important things to consider in the design of future vaccines. It has led to the search for the critical components of viruses and bacteria as well as cancer cells that are recognized together with MHC molecules. We also understand that the MHC molecules of the vaccinated individuals can influence the result.
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| Attempts are now being made to vaccinate against recurrence and spread of certain forms of cancer within the body, metastasis. After surgical removal of a tumor, patients may still have small colonies of residual tumor cells in their bodies. Critical parts of proteins in the cancer cells are identified and used for vaccination in the hope of stimulating T killer cells that can attack the residual cancer cells. It is then essential to type for the MHC molecules of the patient. Only the "correct combinations" of antigen and MHC molecule are expected to work, just as in the original discovery of Doherty and Zinkernagel. | |
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