Reconceiving autoimmunity: An overview

Three interconnected positions are advocated: (1) although serving as a useful model, the immune self does not exist as such; (2) instead of a self/nonself demarcation, the immune system 'sees' itself, i.e., it does not ignore the 'self' or attack the 'other;' but exhibits a spectrum of responses, which when viewed from outside the system appear as discrimination of 'self' and 'nonself' based on certain criteria of reactivity. When immune reactions are conceived in terms of normal physiology and open exchange with the environment, where borders dividing host and foreign are elusive and changing, host defense is only part of the immune system's functions, which actually comprise two basic tasks: protection, i.e., to preserve host integrity, and maintenance of organismic identity. And thus (3) if the spectrum of immunity is enlarged, differentiating low reactive 'autoimmune' reactions from activated immune responses against the 'other' is only a matter of degree. Simply, all immunity is 'autoimmunity,' and the pathologic state of immunity directed at normal constituents of the organism is a particular case of dis-regulation, which appropriately is designated, autoimmune. Other uses of 'autoimmunity' and its congeners function as the semantic remnants of Burnet's original self/nonself theory and should be replaced. A new nomenclature is proposed, concinnity, which more accurately designates the physiology of the animal's ordinary housekeeping economy mediated by the immune system than 'autoimmunity' when used to describe such normal functions.