Autoimmune Pathological Process

Autoimmune Pathological Process

The autoimmune pathological process may be initiated and maintained by (a) autoantibodies, (b) immune complexes con-taining autoantigens, and (c) autoreactive T lymphocytes. Each of these immune processes plays a major role in certain diseases or may be synergistically associated, particularly in multiorgan, systemic autoimmune diseases.

1. Autoantibodies: Autoantibody associated diseases arecharacterized by the presence of autoantibodies in the individ-ual’s serum and by the deposition of autoantibodies in tissues. Autoantibodies may be directly involved in the pathogenesis of certain diseases, while in others they may serve simply as dis-ease markers without a known pathogenic role. They may also be instrumental in triggering various pathogenic mechanisms leading to tissue injury and cell death. Autoantibodies play a key role in the pathogenesis of (a) myasthenia gravis, (b) pem-phigus vulgaris, and (c) various autoimmune cytopenias.

2. Immune complexes containing autoantigens: The forma-tion of immune complexes between self-antigens and autoan-tibodies, leading to end organ damage, is another pathogenic mechanism seen in autoimmune disorders. Only those immune complexes that are of adequate size manage to activate the com-plement system and are involved in the pathogenesis of autoim-mune diseases. Systemic lupus erythematosus and polyarteritis nodosa are two classic examples of autoimmune diseases in which immune complexes play a major pathogenic role.

3. Autoreactive T lymphocytes: Antigens that are seques-tered from the circulation, and are therefore not seen by the developing T cells in the thymus, do not induce self-tolerance. Exposure of mature T cells to such normally sequestered anti-gens at a later time might result in their activation. Induction of autoantibodies to sperms after vasectomy, sympathetic oph-thalmitis, and the presence of antibodies to myocardial cells after myocardial infarction are the examples.

Inappropriate expression of class II MHC molecules can also sensitize self-reactive T cells in certain other situations. This is sup-ported by the clinical observations showing increased frequency of autoimmune diseases in families and by increased rates of clini-cal concordance in monozygotic twins. Polyclonal B-cell activa-tion may also lead to initiation of autoimmune disease process.