This chapter discusses the underlying causes of autoimmunity, focusing on infection and genetic predisposition. It seeks to understand how autoimmunity is normally avoided, and why do some B and T lymphocytes do not recognize and respond to 'self' antigens, considering that their receptors are produced by a random recombination of genes and should be able to recognize virtually everything, instead of being unresponsive, or tolerant, to self. The chapter begins by analyzing the polyclonal activation of anti-self B or T lymphocytes. It then looks into the activation of T lymphocytes by antigens closely similar to self: molecular mimicry. The chapter then shifts to detail the release of sequestered antigens, and displays one of the striking findings in organs affected by autoimmunity, the appearance of MHC class II antigens on cells where they are normally absent. Finally, the chapter reviews the anomalous cytokine production, autoimmune disease, and genetics.
