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The immune system generally does an excellent job of differentiating between self and non-self. In so doing, it destroys mutant cells (cells, in essence, becoming non-self) and invaders. In certain circumstances, the immune system breaks down and no longer leaves self alone; this is auto-immunity-the defense system attacks self. In studying these exceptions, some aspects of the magnificent complexity of the immune system and of the molecular biology of life become apparent.Given that evolutionary processes build on prior experience and mechanisms, it is not surprising that human cells have much in common with yeast, and bacteria molecules found in lower organisms resemble, sometimes quite closely, homologous molecules in human cells. Microbes contain molecules resembling those used by mammalian cells, perhaps because some pathogens use or subvert mammalian systems. These similarities may be sufficient to interfere with the immune system’s ability to discern between self and non-self. Thus, the immune response to certain components of pathogens may recognize the host, a phenomenon called molecular mimicry. This mechanism may be involved in the pathogenesis of rheumatologic and other immune-mediated diseases.