On genetic components in autoimmunity: a critical review based on evolutionarily oriented rationality

The immune system furnishes the organism with the utmost effective defence mechanisms against "foreign" and changes in "self" without doing self-harm. However, optimized efficacy in the defence against the immense variety of "foreign" antigens generates a higher risk for inadvertent self challenge. Such inherent short-comings are the inevitable burden traded for the benefits of an optimally organized defence system. The central molecules involved in specific immune reactions include antigen receptors of B and T lymphocytes, and antigen-presenting proteins encoded by the major histocompatibility complex (MHC; in man HLA). The genetics and evolution of these multigene families is discussed here with respect to their potential contributions to disturbances of "self" recognition. Simple molecular biological tools and procedures for efficiently screening the immunologically relevant genes are described.