Pathogenesis

Current views favor an autoimmune-mediated reaction against the myelin (immunologic attack against self-antigen) involving both cellular and humoral immunity. This autoimmune mechanism is supported by similarities between the pathology of MS and the experimental allergic encephalomyelitis (EAE) induced by immunization with brain and spinal cord myelin extracts.

The cellular immune reaction is mediated by T lymphocytes. Simplistically, activated CD4+ T lymphocytes possessing antigen-specific receptors cross the blood-brain barrier and react with myelin and/or oligoden-droglia antigen. Cytokines released by T lymphocytes activate macrophages expressing MHC class II antigen. These macrophages present the myelin antigens to the T cells and, in time, remove the products of myelin disintegration. MBP, proteolipid protein, and myelin oligodendrocyte glycoprotein are major target antigens. The humoral immune reaction is mediated by activated B lymphocytes that secrete myelin-specific antibodies. Several pathogens have been postulated to trigger the immune reaction: measles virus, Epstein-Barr virus, human herpes virus 6, retroviruses, canine distemper virus, and Chlamydia pneumoniae. None has yet been confirmed.

An alternative view regarding the pathogenesis of MS implicates apoptotic oligodendroglial deaths and subsequent microglial activation as early events in plaque formation.

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