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THEORI AUTOIMUN (PATOGENITAS DAN FAKTOR)

CENNIKON PAKPAHAN (110100299)

Beberapa teori yang diyakini menjadi penyebab autoimun adalah:

- Inaccessible Self-AntigensTeori 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 FunctionAutoimmune 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 antigen-

specific . 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, myastheniagravis, 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 MimicryAnother 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

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streptococcal bacterial antigens cross-react with antigens from cardiac muscle phenomenon

known as molecular mimicry.

- Polyclonal B-Cell ActivationLoss 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-DNAantibodies in lupus erythematosus, and other autoantibodies has been described after

bacterial, viral, and parasitic infections.

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