The Immunobiology of Multiple Sclerosis

Multiple sclerosis (MS) is the most common nontraumatic cause of neurological deficits among young adults in the Western World. MS likely results from an organ-specific inflammatory attack of autoimmune nature against components of the central nervous system (CNS), with ensuing neurological deficits, and with time, development into a progressive disease course. More than 100 genetic variants connected to immune function predispose for the disease, as well as lifestyle/environmental factors. HLA class II genes provide the strongest impact, controlling CD4 + T cells, though, in addition there are associations to class I genes as well with a potential role of CD8 + T cells. Pathogenesis involves focal invasion of T cells into the CNS that upon recognition of so far undefined antigens are reactivated and secrete proinflammatory cytokines and chemokines recruiting additional cell types. These include macrophages that are important effector cells damaging not only myelin, but also nerve fibers. Current knowledge of key mechanisms in neuroinflammation has led to a series of modestly or highly effective treatments, though some of them, due to their broad action in the immune system, can lead to serious adverse events. Further detailed knowledge on MS-specific mechanisms is needed to develop more selective treatments with improved effect/risk profiles.