Immunology of Multiple Sclerosis

Multiple sclerosis (MS) is clearly linked to the immune system. This has been demonstrated by the beneficial responses to treatments that dampen the immune system. This chapter summarizes the numerous changes in the immune system that are associated with the development of MS. The human immune system has two major divisions, the innate and the adaptive arms, and each is implicated in the pathogenesis of MS. Herein, we discuss mechanisms by which both arms contribute to lesion formation in MS. The adaptive immune system, which responds to specific antigenic targets, provides immune “memory” for subsequent exposures and thereby protecting against future exposures to the same or similar targets. This arm of the immune system is implicated in MS because its major cells, lymphocytes, are found in active central nervous system (CNS) MS lesions and also in the cerebrospinal fluid during MS activity. T lymphocytes can be divided into CD4+ and CD8+ T cells, and each is present in active MS lesions. In addition, the main animal model of MS, experimental autoimmune encephalomyelitis (EAE), can be transferred by myelin-specific T cells. B lymphocytes are also critical to MS, as deleting them in the blood can greatly reduce MS clinical and radiological activity. Innate immune cells process and present antigens to T cells in order to initiate and propagate tissue-specific damage. In addition, effector mechanisms employed by a variety of different innate cells, including macrophages and microglia, directly lead to myelin and neuronal injury during the genesis of MS lesions. Divisions between various innate cells impart features that contribute to inflammatory destruction as well as recovery from injury in MS. Overall, a complex interplay between immune cells serves to coordinate a complex cascade of inflammatory events that contribute to development of disease in MS.