title: The pathogenesis of multiple sclerosis: reconsideration of the role of viral agents and defence mechanisms.
abstract: Numerous ubiquitous ribonucleic acid and deoxyribonucleic acid viruses, inducing acute, monophasic infections (mostly childhood diseases) have been considered as potential causes of multiple sclerosis. The present hypothesis reconsiders the role of the viral agent: not the virus, but the reaction of the defense system to the viral persistence, appearing after the acute phase, is postulated as a key factor. A prerequisite of multiple sclerosis is polygenetically determined or acquired immunodeficiency; the defense system is not able to stop repeated viral reactivations induced by a set of exogenous and/or endogenous factors. Thus, an aberrant virus production can appear repeatedly. If the virus spreads from primary target--the lymphoreticular system--into the central nervous system, the multiple sclerosis process can be initiated. Activated T cells and endothelial cells serve as first-host cells. Their infection triggers a set of reactive events: multiple microthrombosis and inflammation play a key role, both of which can result in nonspecific degradation of the myelin. An increased release of myelin antigens induces a homeostatic autoimmunity. Long-term repetition of the shifts and the infection of inflammatory cells can lead to disturbances in self-tolerance. A dysregulated pathological autoimmunity can develop, which acts as a main effector of the specific demyelination.
authors.affiliation: Max Planck Institute for Psychiatry, Martinsried, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Simon
authors.forename: W J
authors.initials: WJ
authors.lastname: Neubert
mesh_terms: D000163:Acquired Immunodeficiency Syndrome; D002648:Child; D004267:DNA Viruses / Q000472:pathogenicity; D003711:Demyelinating Diseases / Q000276:immunology / Q000821:virology; D004727:Endothelium / Q000502:physiology; D006801:Humans; D007249:Inflammation; D008213:Lymphocyte Activation; D008954:Models, Biological; D009103:Multiple Sclerosis / Q000276:immunology* / Q000821:virology*; D013601:T-Lymphocytes / Q000276:immunology; D013927:Thrombosis