Autoimmunity and hypothyroidism

Primary myxedema and hypothyroid Hashimoto's disease provide a well-documented example of organ-specific autoimmunity in man. Very slight modifications or increased release of thyroglobulin or thyroid antigens in the circulation may cause the rupture of autotolerance for the normal thyroid components, at least when individuals have a genetic predisposition to autoimmune thyroiditis (possibly associated with a predisposition to other autoimmune diseases). The demonstration of an association between HLA and thyroiditis, however, requires additional studies. The basic immunological abnormality responsible for autoimmunization against thyroid components is a defect in suppressor T cells, shown in experimental animals but not firmly established in man. The result of autoimmunization will be the appearance of cytotoxic mechanisms that lead to destruction of the thyroid follicle with progressive fibrosis, antibody-dependent cell-mediated cytotoxicity apparently being of major importance. A recent report shows, in addition, that thyroid atrophy in primary hypothyroidism is associated with the production of antibodies that block the thyroid-growth-promoting activity of TSH. The recent progress made in our understanding of autoimmune thyroiditis will certainly contribute to improving our knowledge of how and when autoimmunization might develop in man.     

Tolerance and Autoimmunity

Long-lasting tolerance can be produced by prenatal or perinatal exposure to foreign antigens. Self-tolerance results from embryonic exposure to antigens of the host itself. Several mechanisms that contribute to self-tolerance have been described. They include clonal deletion, anergy, and active suppression. A failure in these mechanisms may lead to autoimmune disease. Some important human diseases are associated with autoimmunity, and immunomethods are regularly employed for their diagnosis. In the future immunomethods will prove to be valuable for the identification of subjects at risk of developing autoimmune disease, thereby permitting preventive interventions.     

Microbial Adjuvant and Autoimmunity

Definite lesions in the exocrine pancreas were produced when SMA mice were immunized eight times at intervals of 30 days with a mixture of extract of pooled pancreas from syngeneic mice and the capsular polysaccharide of Klebsiella pneumoniae type 1 Kasuya strain (CPS-K), whereas no pancreatic lesions were produced in mice given CPS-K alone or pancreatic extract alone. The typical histological changes were characterized by infiltration with lymphocytes, plasma cells, and other mononuclear cells, degeneration and lysis of the acinar cells, destruction of the lobular architecture, and replacement by fatty tissue and fibrous connective tissue. The endocrine islets were well preserved. No specific histological changes were produced in the organs other than the pancreas in these mice. Most of mice immunized with pancreatic extract mixed with CPS-K produced serum precipitins to syngeneic pancreatic antigens. However, severe pancreatic lesions were also produced in mice showing no definite precipitin production.     

Microbial Adjuvant and Autoimmunity

With the use of the capsular polysaccharide of Klebsiella pneumoniae (CPS-K) as a powerful adjuvant, high precipitin responses could be induced in mice to syngeneic eyeball extracts and thyroid gland extracts which were normally nonimmunogenic. Only very weak responses were induced to eyeball extracts by Freund's complete adjuvant. Repeated administrations of the antigens mixed with CPS-K at time intervals of 30 days (more than twice for the eyeballs or more than three times for the thyroid glands) were required for induction of high precipitin responses. Antibody responses detectable by the immunofluorescent technique could be induced to syngeneic lymphoid tissue extracts by injecting the mixture of antigen and CPS-K more than five times at time intervals of 30 days. These findings suggest that repeated stimulation by autoantigens together with such a strong adjuvant as CPS-K can terminate natural tolerance against autoantigens.