Immunopathogenesis

Although the precise etiology of multiple sclerosis (MS) remains unknown, three factors are involved. The first is genetic vulnerability. Over 230 risk/susceptibility genes, along with occasional protection and disease severity genes, are being identified at an increasing pace. They are typically linked to immune/inflammatory rather than central nervous system (CNS) factors. Linked genes are not universal and can vary based on patient racial, ethnic, and geographic background. The second factor involves environmental exposures, which probably occur at critical time points especially earlier in life. These include vitamin D deficiency, Epstein-Barr virus (EBV) infection, adolescent obesity, smoking, and ultraviolet light exposure. The final factor is the host immune system, which damages the CNS. MS is clearly an immune-mediated disease. It appears to be heterogeneous, however, with different pathways leading to disease expression (Barnett et al., Int MS J 16:57–65, 2009). Studies focused on pathology and immunology allow important insights into MS pathogenesis and pathophysiology. This chapter will begin with a review of the neuropathology of MS and then cover current concepts on major immunologic disease factors involved. Distinctions between relapsing and progressive MS will be highlighted.