T cell reactivity to MHC molecules: immunity versus tolerance

Article Abstract:

Molecules of the major histocompatibility complex (MHC) were first discovered in conjunction with, and derive their name from, their role in the rejection of grafted tissues by the host. Further research has demonstrated that these molecules play an important role in virtually all immune reactions, many of which stringently require the appropriate MHC molecules for a T-cell response. Under normal conditions, peptide fragments of foreign proteins are presented to antigen-specific T-cell receptors by the MHC molecules. However, the MHC molecules are equally good at binding and presenting self molecules. Although the study of how the immune system learns to ignore these self antigens, resulting in immunological tolerance to the body's own tissues, has been intense for years, the question is not resolved. Since it is experimentally quite difficult to study the normal induction of tolerance to self antigens, most researchers study the experimental induction of tolerance to foreign antigens, and hope that the results will provide insight into the natural process, as well. Among the best foreign antigen molecules for study are foreign MHC molecules themselves, because a disproportionately large number of T cells react with these antigens. In a review of the current state of research on the induction of tolerance to foreign antigens, the authors show how tolerance is more difficult to achieve in mature T cells than immature, but that it may be achieved with careful choices of foreign MHC molecules on atypical cells. Tolerance induced in this way, however, is not complete, and it is not known to what degree, and through what means, tolerance may be induced in mature T cells. (Consumer Summary produced by Reliance Medical Information, Inc.)

Immune response

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Autoimmune diseases: the failure of self tolerance

Article Abstract:

Insulin-dependent diabetes, multiple sclerosis, rheumatoid arthritis, myasthenia gravis, and psoriasis might seem to have little in common, but all are believed to result from a patient's misguided immune system erroneously attacking his own cells or tissues. All in all, over 40 disease are either known or suspected to be caused by autoimmune mechanisms. In a review of the current state of understanding autoimmune disease, the authors discuss how genetic factors, immunological factors, and environmental factors might interact to result in an autoimmune disease. Most autoimmune diseases are found to be more likely among people with some histocompatibility genes than with others. A few, like ankylosing spondylitis and psoriasis, are associated with particular Class I molecules of the major histocompatibility complex (MHC); the majority are associated with specific Class II molecules. In some cases, the disease is caused by autoantibodies, such as is true of myasthenia gravis, while in others the illness is the result of autoreactive T cells, as in insulin-dependent diabetes mellitus. The association with MHC molecules is far from absolute, however, and there is much evidence that environmental factors are at work. In particular, many common bacteria and some viruses seem to be capable of initiating autoimmune diseases in susceptible individuals. Some investigators believe that this can result from immunologic similarities, or cross reactions, between the infecting organism and some components of normal body tissues. However, details of how the normal mechanisms of self-tolerance fail in patients with autoimmune disease are far from clear. (Consumer Summary produced by Reliance Medical Information, Inc.)

Autoimmune diseases

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Clonal deletion versus clonal anergy: the role of the thymus in inducing self tolerance

Article Abstract:

One of the fundamental problems of immunology is discerning the mechanisms by which the immune system recognizes and responds to foreign antigens, sometimes called ''nonself'' antigens, while tolerating self antigens within the body. Over 30 years ago, Burnet suggested that one mechanism might be the elimination of self-reactive cells early in development. More recently, it has become clear that not all self-reactive T cells are completely eliminated; some are simply rendered inactive. This functional inactivation, called clonal anergy, is, like the elimination of self-reactive cells by clonal deletion, accomplished during the development of the thymus. In a review of the current understanding of this complex process, the authors describe the interaction of the T-cell receptors with molecules of the major histocompatibility complex, the intracellular signals, and the variety of different cell types which contribute to the development of clonal anergy and the immunological tolerance of self antigens. (Consumer Summary produced by Reliance Medical Information, Inc.)

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