The mechanisms for achieving self/non-self distinction include clonal deletion, clonal anergy, and clonal balance. Clonal deletion results in the elimination of self-reactive T cells during their maturation in the thymus. T cells reactive with self-antigens not represented in the thymus, and probably some low-affinity T cells, escape clonal deletion and populate peripheral lymphoid tissues and blood. These self-reactive T cells are normally held in check by clonal anergy or clonal balance. Anergy occurs when a T cell receives its antigen-specific signal in the absence of required co-stimulatory signals. Clonal balance depends upon the ratio of stimulatory and inhibitory signals delivered to the T cells. Self-tolerance of B cells probably depends upon similar mechanisms, but is less effective. Autoantibodies, therefore, are more common than self-reactive T cells. Autoimmune disease results from an attack on the host's own tissues by self-reactive T cells or antibodies. Autoimmune thyroid disease is a well-characterized paradigm of disease caused by autoimmunity. Graves' disease results from an over-active thyroid gland produced by autoantibodies directed to the receptor for the thyroid-stimulating hormone. Hashimoto's thyroiditis is associated with thyroid damage produced by self-reactive T cells directed to thyroglobulin or, possibly, thyroperoxidase. The disease can be reproduced in experimental animals by immunization with autologous thyroglobulin, providing firm evidence that the thyroiditis is caused by autoimmunization. The etiology of autoimmune disease is multifactorial and includes both genetic and environmental factors. Several genes are involved, affecting both immune regulation and vulnerability of the target organ. Among the environmental factors are infectious agents, drugs, diet, and toxins. Hormones and even emotional status also play a role. Both T cells and antibodies are involved in the pathogenesis and the demonstration of autoantibodies is useful in diagnosis. Future treatment and prevention of autoimmune disease depends upon precise delineation of the pathogenic determinants of the antigens.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)