Autoimmune mechanism of MS. Naive, myelin reactive T cells are activated by microbes that: 1) induce the innate immune system to provide costimulatory signals necessary for clonal expansion of naive CD4⁺ T cells and, 2) contain epitopes that are cross-reactive with self antigens. Activated CD4⁺ T cells cross the blood-brain barrier and recognize self antigen presented by microglia, local antigen-presenting cells (APC) that sample self antigens. The reactivation of autoreactive CD4⁺ cells leads to a cascade of events including recruitment of macrophages, antibody secretion, and eventual destruction of myelin and axons.