The underlying basic mechanisms of autoimmune reactivity have been puzzling immunologists for decades. What makes the immune system, which has evolved over the millennia to combat the assaults of invading microorganisms, turn against the organism itself? It now seems clear that avoiding autoreactivity while maintaining immunocompetence is a complex assignment that can sometimes go wrong. Although the innate and adaptive branches of the immune system have been involved in the induction and evolution of autoimmunity, it is well accepted that adaptive (T and B cells) responses are the main initiators and regulators of autoimmunity.