Myelin immune-mediated

Griffin JW, George R, Lobato C, Tyor WR, Yan LC, Glass ID (1992) Macrophage responses and myelin clear ance dining Wallerian degeneration Relevance to immune-mediated demyelination. J Neuroimminiol 40 153—165. 

ADEM acute disseminated encephalomyelitis is an immune mediated disease of brain. It is brief but significant and results in direct myelin damage. It usually occurs following a viral infection or vaccination (commonly for measles, mumps or rubella), but it may also appear spontaneously. 

The net physiological consequences of immune-mediated myelin disruption are partial or total conduction block, slowing of conduction, and ephaptic cross-activation due to disruption of salutatory conduction mediated by the nodes of... 

In brief, EAE can be induced by immunization with several encephalitogenic proteins from myelin, most notably MBP, PLP and myelin-oligodendrocyte glycoprotein (MOG). MBP was the first protein shown to cause EAE, and this classical form of the disease is mediated primarily by CD4+, MHC class II restricted T cells, because it can be transferred from an immunized animal to a naive animal using these cells. These data document the importance of CD4+ lymphocytes for EAE induction, but additional pathogenic roles for other T cell populations are possible, especially in later stages of the disease. Also, there is... 

The molecular mechanism by which IFN-/1 induces its therapeutic effect is complex and not fully understood. It is believed that the pathology of multiple sclerosis is linked to the activation and proliferation of T lymphocytes specific for epitopes found on specific myelin antigens. Upon migration to the brain, these lymphocytes trigger an inflammatory response mediated by the production of pro-inflammatory cytokines, most notably IFN-y, IL-1, IL-2 and TNF-a. The inflammatory response, in addition to other elements of immunity (e.g. antibodies and... 

Lider, O., Santos., L. M., Lee, C. S., Higgins, P. J., and Weiner, H. L. 1989. Suppression of experimental autoimmune encephalomyelitis by oral administration of myelin basic protein, II. Suppression of disease and in vitro immune responses is mediated by antigen-specific CD8+ T lymphocytes. J. Immunol 142 748-752. 

In addition to the effect of increased VLCFA on membrane and possibly cellular function, the rapid cerebral form of X-ALD is characterized by an inflammatory response that is believed to contribute to the demyelination that characterizes this phenotype and which is similar to that seen in multiple sclerosis. These cerebral lesions are characterized by breakdown in myelin with sparing of the axons accompanied by the accumulation of cholesterol ester in the neurons. A perivascular inflammatory response with infiltration of T cells, B cells, and macrophages also is present. Therefore, it is believed that the rapid cerebral disease has an im-munologically-mediated component. It has been suggested that the inflammatory response occurs in response to the elevated levels of VLCFA in lipids, which elicits an inflammatory cascade that may be mediated in part by cytokines. Once this cascade begins, it may be more difficult to intervene in the disease process, and in general therapeutic interventions studied to date have been most effective when initiated early. Therefore, prevention of the initiation of the immune response is important for improving outcome. 

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