Immune responses in the central nervous system

Abstract

Immune responses occurring within the central nervous system (CNS) have unique features attributable to the cellular and functional organization of the CNS and to the presence of the blood-brain barrier. Immune responses to viral infection of the CNS involve the participation of most immunologically important cells: T and B lymphocytes, monocytes, and natural killer cells. Normally, helper/inducer T lymphocytes are predominant in the cerebrospinal fluid (CSF) and in perivascular cuffs. After stimulation with antigen in tissue, these cells produce lymphokines, which stimulate mast cells to open capillary tight junctions, stimulate proliferation of lymphocytes, and attract monocytes and B lymphocytes. B lymphocytes mature into immunoglobulin-producing cells that secrete antibody locally which appears in the CSF. Cytotoxic/suppressor T lymphocytes, which damage antigen-containing cells, are predominant in immunopathologic reactions. In other situations the immune response targets normal CNS tissue rather than foreign antigens. Two general types of reactions may be seen: (1) vasculitis with destruction of vessel walls and infarction, and (2) perivascular inflammation with demyelination. The former is associated with immune complex deposition, and the cellular infiltrate includes polymorphonuclear leukocytes. The inflammation associated with perivenular demyelination is composed almost exclusively of mononuclear leukocytes. In the diseases for which pathogenetic mechanisms are understood, cells become sensitized to myelin constituents and induce local demyelinating lesions in which the damage is effected by macrophages. It is not clear whether macrophages are directed in this destructive effort by lymphokines or immunoglobulins or both.