[Pathogenesis of multiple sclerosis: status of research].
Multiple sclerosis is considered an immune-mediated disease of the CNS white matter. Peripheral blood and CSF contain circulating autoreactive T lymphocytes recognizing a number of myelin antigens. When activated, e.g. through a viral infection, these cells can migrate across the blood-brain-barrier into the CNS. Upon encounter of microglial cells and local reactivation, they undergo clonal proliferation. Secreted Th1 cytokines (IFN-gamma and TNF-alpha) stimulate macrophages and microglia to heightened phagocytic activity and the release of proinflammatory mediators. This results in damage to the myelin sheath and oligodendrocytes. Autoantibodies directed to myelin antigens are of key importance in the demyelinative process by initiating the complement cascade. Early in the course of the disease, down-regulatory mechanisms can terminate an acute exacerbation and contain tissue damage. With repeated attacks, these mechanisms get overwhelmed and the reparative capacity of oligodendrocytes exhausted. This marks the transition to the chronic progressive phase of the disease characterized pathologically by demise of oligodendrocytes, secondary loss of axons and astroglial proliferation. A better understanding of the pathogenesis of MS allows to identify strategic targets for more specific and efficacious therapeutic immunointervention.
Hartung
H P
HP
Klinischen Forschungsgruppe für Multiple Sklerose und Neuroimmunologie, Bayerischen Julius-Maximilians-Universität Würzburg, Deutschland.
D001323:Autoantibodies / Q000134:cerebrospinal fluid; D001921:Brain / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology; D009103:Multiple Sclerosis / Q000276:immunology*; D009185:Myelin Proteins / Q000276:immunology; D009186:Myelin Sheath / Q000276:immunology; D009836:Oligodendroglia / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D001323:Autoantibodies; D009185:Myelin Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
Pathogenese der Multiplen Sklerose: Stand der Forschung.