Immune regulation of multiple sclerosis

Abstract

Multiple sclerosis (MS) is considered a prototype inflammatory autoimmune disorder of the central nervous system (CNS). The etiology of this disease remains unknown, but an interplay between as yet unidentified environmental factors and susceptibility genes appears most likely. In consequence, these factors trigger a cascade, involving an inflammatory response within the CNS that results in demyelination, oligodendrocyte death, axonal damage, gliosis, and neurodegeneration. How these complex traits translate into the clinical presentation of the disease is a focus of ongoing research. The central hypothesis is that T lymphocytes with receptors for CNS myelin components are driving the disease. The initial activation of autoreactive lymphocytes is thought to take place in the systemic lymphoid organs, most likely through molecular mimickry or nonspecifically through bystander activation. These autoreactive lymphocytes can migrate to the CNS where they become reactivated upon encountering their target antigen, initiating an autoimmune inflammatory attack. This ultimately leads to demyelination and axonal damage. This chapter focuses on the role of T and B lymphocytes in the immunopathogenesis of MS.

Keywords: B-cells; Innate immunity; T-cells; adaptive immunity; blood-brain barrier; chemokines; cytokines; macrophages; matrix metalloproteinases.