Autoimmunity refers to immune reactions against self (“auto”) antigens. Autoimmune diseases are estimated to affect at least 1% to 2% of the U.S. population. The evidence that these diseases are indeed the result of autoimmune reactions is more persuasive for some than for others. For instance, in many of these disorders, high-affinity autoantibodies have been identified, and in some cases these antibodies are known to cause pathologic abnormalities. There is also growing evidence for the activation of pathogenic self-reactive T cells in some of these diseases. In addition, experimental models have proved very informative, providing circumstantial evidence supporting an autoimmune etiology. Nevertheless, it is fair to say that for many
Table 5.7 Autoimmune Diseases
Inflammatoryboweldiseases(Crohndisease,ulcerativecolitis) *AroleforTcellshasbeendemonstratedinthesedisorders,butantibodiesmayalsobeinvolvedintissueinjury.
†Anautoimmunebasisofthesedisordersissuspected,butthesupportingevidenceisnotstrong.
‡Thesedisordersmayresultfromexcessiveimmuneresponsestocommensalentericmicrobes,autoimmunity,oracombinationofthetwo.
disorders traditionally classified as autoimmune, this etiology is suspected but not proved.
Autoimmune diseases may be organ-specific, in which the immune responses are directed against one particular organ or cell type and result in localized tissue damage, or systemic, characterized by lesions in many organs ( 5.7 ). In systemic diseases that are caused by immune complexes and autoantibodies, the lesions principally affect the connective tissues and blood vessels of involved organs. Therefore, these diseases are often referred to as collagen vascular diseases or connective tissue diseases, even though the immunologic reactions are not specifically directed against constituents of connective tissue or blood vessels.
Normal persons are unresponsive (tolerant) to their own (self) antigens, and autoimmunity results from a failure of self-tolerance. Therefore, understanding the pathogenesis of autoimmunity requires familiarity with the mechanisms of normal immunologic tolerance.
Immunologic tolerance is a state of unresponsiveness to an antigen that is induced by exposure of specific lymphocytes to that antigen. Self-tolerance refers to lack of immune responsiveness to one’s own tissue antigens. Billions of different antigen receptors are randomly generated in developing T lymphocytes and B lymphocytes, and it is not surprising that during this process, receptors are produced that can recognize self antigens. Since these antigens cannot all be concealed from the immune system, there must be a means of eliminating or controlling self-recognizing lymphocytes. Several mechanisms work in http://ebooksmedicine.net
Thymus Development Treg of regulatory T cells
Anergy (failure to Anergy respond) BB (failure to
Fig. 5.19 Mechanisms of immunologic tolerance to self antigens. The principal mechanisms of central and peripheral self-tolerance in T cells and B cells are illustrated. APC, Antigen-presenting cell; Treg cells, regulatory T cells.
concert to select against self-reactivity and to thus prevent immune reactions against the body’s own antigens. Two broad mechanisms are recognized: central tolerance and peripheral tolerance (
Fig. 5.19