A model of MS pathogenesis. T cells become activated in the periphery by processed peptides expressed by antigen-presenting cells in the context of MHC molecules (see inset). In MS, these peptides are thought to mimic the molecular shape of some CNS antigens. Activated T cells undergo transcriptional changes resulting in the expression of adhesion molecules and proteolytic enzymes that favor their adhesion to the basal lamina of the capillary vessels of the blood-brain barrier. The T cells then pass out of the blood vessels (extravasation) to the brain parenchyma where they are reactivated by astrocytes or microglial cells now presenting CNS antigens. This second activation step triggers a new wave of inflammation in which numerous cytokines, chemokines, and other molecules such as NO, glutamate, and free radicals are produced. This process is maintained by positive feedback loops acting on effector cells, and eventually results in damage to myelin, oligodendrocytes, and neurons.
Baranzini and Hauser Genome Biology 2002 3:reviews1027.1 doi:10.1186/gb-2002-3-10-reviews1027