Multiple sclerosis -- a coordinated immune attack across the blood brain barrier

Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS). The acquired immune system plays a central role in the pathogenesis of MS although target antigens and effector mechanisms are still poorly defined. Studies in animal models of infectious or autoimmune encephalomyelitis suggest that the acquired immune response targeting the CNS in MS originates from the periphery. Both T and B cells undergo activation and maturation in the lymphoid system allowing them to cross the blood brain barrier and infiltrate CNS tissue. Within the CNS, they require a local proinflammatory milieu contributed by macrophages and microglia to mediate their effector function which ultimately leads to damage of myelin sheath, oligodendrocytes, and neurons. In the current review, we elucidate the role of the immune system in MS with particular emphasis on activation and migration of immune cells to the CNS, the role of CNS cells in the inflammatory process and the contribution of the immune system to damage and repair. Based on these considerations we discuss new strategies to investigate pathogenetic pathways in multiple sclerosis.