Early in the last century, paul ehrlich realized that the immune system could go awry and, instead of reacting against foreign antigens, could focus its attack on self-antigens. He termed this condition "horror autotoxicus." We now understand that, while mechanisms of self-tolerance normally protect an individual from potentially self-reactive lymphocytes, there are failures. They result in an inappropriate response of the immune system against self-components termed autoimmunity. In the 1960s, it was believed that all self-reactive lymphocytes were eliminated during their development in the bone marrow and thymus and that a failure to eliminate these lymphocytes led to autoimmune consequences. Since the late 1970s, a broad body of experimental evidence has countered that belief, revealing that not all self-reactive lymphocytes are deleted during T-cell and B-cell maturation. Instead, normal healthy individuals have been shown to possess mature, recirculating, self-reactive lymphocytes. Since the presence of these self-reactive lymphocytes in the periphery does not inevitably result in autoimmune reactions, their activity must be regulated in normal individuals through clonal anergy or clonal suppression. A breakdown in this regulation can lead to activation of self-reactive clones of T or B cells, generating humoral or cell-mediated responses against self-antigens. These reactions can cause serious damage to cells and organs, sometimes with fatal consequences.
Sometimes the damage to self-cells or organs is caused by antibodies; in other cases, T cells are the culprit. For example, a common form of autoimmunity is tissue injury by mechanisms similar to type II hypersensitivity reactions. As Chapter 16 showed, type II hypersensitivity reactions involve antibody-mediated destruction of cells. Autoimmune hemolytic anemia is an excellent example of such an autoimmune disease. In this disease, antigens on red blood cells are recognized by auto-antibodies, which results in the destruction of the blood cells, which in turn results in anemia. Auto-antibodies are also the major offender in Hashimoto's thy-roiditis, in which antibodies reactive with tissue-specific antigens such as thyroid peroxidase and thyroglobulin cause severe tissue destruction. Other autoimmune diseases that involve auto-antibodies are listed in Table 20-1.
Many autoimmune diseases are characterized by tissue destruction mediated directly by T cells. A well-known example is rheumatoid arthritis, in which self-reactive T cells attack the tissue in joints, causing an inflammatory response that results in swelling and tissue destruction. Other examples include insulin-dependent diabetes mellitus and multiple sclerosis (see Table 20-1).
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