Organ-specific autoimmunity: a 1986 overview

The normally functioning immune system is subject to intricate networks of regulatory mechanisms: it is therefore not surprising to find that autoimmune diseases present a complex pathogenic picture in which the relative contributions of various factors probably determine the precise nature and course of disease. This is particularly evident in the effector mechanisms of organ-specific autoimmunity which are described in this chapter. These ultimately give rise to the disease symptoms, and can be directly cytotoxic, or may either stimulate or block functional activity or growth of the target cells. Their various contributions to human diseases are becoming more firmly established, as in Type I diabetes, or are only now being described, as in the case of EC-Ab in protracted diarrhea of infancy and as evidenced by the growing lists of receptor-stimulating or -blocking antibodies. The nature and precise location of relevant autoantigens is also coming under closer scrutiny. The answers to the question of why these diseases arise in the first place remain more elusive. However, it is again likely that a variety of factors can contribute. The attractive possibility of a role for idiotypic interactions is gaining ground, particularly within the context of antibodies to hormones and their receptors. Another potential mechanism which we believe may be of central importance, particularly in the development of organ-specific destructive autoimmunity, and which we have discussed here in detail, is the aberrant expression of HLA Class II molecules by target cells. Whether this is actually an initiating factor is presently not known, but its potential for promoting pathogenesis both early and late in the process is clear. Furthermore, the complex nature of the regulation of epithelial Class II expression may help to explain the heterogeneity of features and course of disease in different patients with the same underlying pathology. All these advances in our basic understanding of the disease processes should ultimately lead to more effective and specific means of therapeutic intervention.