XXXX as a by-product of the failure to sustain protective autoimmunity: a paradigm shift.

@entity1 @entity149 @entity179 @entity15 @entity792 @entity130
@entity792 are traditionally viewed as an outcome of a chaotic situation in which an individual's immune system reacts against the body's own proteins. In @entity15 , a @entity149 (CNS), the immune attack is directed against myelin proteins. In this article, the authors propose a paradigm shift in the perception of @entity792 . They suggest that an @entity792 may be viewed as a by-product of the malfunctioning of a physiological autoimmune response whose purpose is protective. The proposed view is based on observations by their group suggesting that an autoimmune response is the body's own mechanism for coping with CNS damage. According to this view, all individuals are endowed with the potential ability to evoke an autoimmune response to CNS @entity130 . However, the inherent ability to control this response so that its beneficial effect will be expressed is limited and is correlated with the individual's inherent ability to resist @entity792 induction. The same @entity792 cells are responsible for neuroprotection and for disease development. In @entity1 with CNS @entity130 or @entity179 , it might be possible to gain maximal autoimmune protection and avoid @entity792 induction by boosting the immune response, using myelin-associated peptides that are nonpathogenic or antigens that simulate the activities of such peptides. In @entity1 with @entity15 and other @entity179 , where the aim is to block the @entity792 while deriving the potential benefit of the autoimmune response, the effect of treatment should be immunomodulatory rather than immunosuppressive. In this article, the authors present a novel concept of protective autoimmunity and propose that @entity792 is a by-product of failure to sustain it. They summarize the basic findings that led them to formulate the new concept and offer an explanation for the commonly observed presence of cells and antibodies directed against self-components in healthy individuals. The therapeutic implications of the new concept and their experimental findings are discussed.
