THEORI AUTOIMUN (PATOGENITAS DAN FAKTOR) CENNIKON PAKPAHAN (110100299)

Beberapa teori yang diyakini menjadi penyebab autoimun adalah: Inaccessible Self-Antigens Teori simpel ini menjelaskan hilangnya toleransi di dalam penyakit autoimun The simplest hypothesis to explain the loss of tolerance in autoimmune disease states that an immune reaction develops to a self-antigen not normally accessible to the immune system. Intracellular antigens are not exposed or released until some type of tissue injury releases them. At that time, an immune response develops. Examples of this type of response are antibody formation against spermatozoa, lens tissue, and myelin. Whether these autoantibodies can induce injury directly is another matter. In the case of antisperm antibodies, aside from a localized orchitis, there is no evidence that they induce generalized injury. Thus, although autoantibodies may form against normally sequestered antigens, there is only infrequent evidence that they are pathogenic. - Abnormal T Cell Function Autoimmune reactions have been suggested to develop as a result of abnormalities in the T lymphocyte system. Most immune responses require T cell participation to activate antigenspecific . B cells. Thus, alterations in the number or functional activities of helper or suppressor T cells would be expected to influence one's ability to mount an immune response. In fact, defects in T cells, particularly suppressor T cells, have been described in many autoimmune diseases. For example, there are reports of defective suppressor cell activity in human and experimental SLE. Lymphocytotropic antibodies have also been described in patients with lupus. Abnormalities in suppressor cell function characterize other autoimmune diseases, including primary biliary cirrhosis, thyroiditis, multiple sclerosis, myasthenia gravis, rheumatoid arthritis, and scleroderma. However, the critical question is whether these alterations in suppressor cell function cause these diseases or whether they merely represent an epiphenomenon. Defects in suppressor cell function have also been described in persons with no evidence of autoimmune disease. There has also been interest in abnormalities in helper T cell function in autoimmune disease. Helper T cells are defined by their role in antigen-specific B cell activation. It is believed that these cells maintain the helper T cell tolerance induced by low doses of antigen. Recent evidence indicates that these cells become autoreactive in many autoimmune diseases. One key mechanism in autoimmunity is DNA hypomethylation caused by drugs and other agents. This effect leads to upregulation of leukocyte function antigen 1 (LFA-1) and B cell activation independent of antigen. An example of this T cell autoreactivity and loss of antigen specificity is drug-induced lupus. Experimentally, it is also possible to break this type of tolerance by altering an antigen so that the helper cell is activated and triggers the B cells. An example is when an antigen is modified by partial degradation or complexing with a carrier protein. Some rheumatic diseases are marked by autoantibodies to partially degraded connective tissue proteins, such as collagen or elastin. In some drug-induced hemolytic anemias, antibody against a drug causes hemolysis when the drug binds to erythrocyte membranes. - Molecular Mimicry Another mechanism by which the helper T cell tolerance is overcome involves antibodies against foreign antigens that cross-react with self-antigens. Here helper T cells function correctly and do not induce autoantibody formation. Rather, the efferent limb of the immune response is abnormal. Thus, in rheumatic heart disease, antibodies against -

streptococcal bacterial antigens cross-react with antigens from cardiac muscle phenomenon known as molecular mimicry. - Polyclonal B-Cell Activation Loss of tolerance may also involve polyclonal B cell activation, in which B lymphocytes are directly activated by complex substances that contain many antigenic sites (e.g., bacterial cell walls and viruses). Development of rheumatoid factor in rheumatoid arthritis, anti-DNA antibodies in lupus erythematosus, and other autoantibodies has been described after bacterial, viral, and parasitic infections. -