title: [Immunology for understanding the pathogenesis of multiple sclerosis].
abstract: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) and the pathogenesis leading to demyelination includes 3 major processes. The first step is establishment of autoimmunity to CNS myelin components, with molecular mimicry between a portion of the infectious agents and that of myelin, which is an important feature. The second step is entry of immune cells into the CNS via the blood-brain barrier (BBB). Activated T cells can easily cross the BBB using surface LFA-1 and VLA-4 as ligands to ICAM-1 and VCAM-1, respectively, which are expressed on endothelial cells in the CNS. As the third step, immune reactions occur within the CNS when activated T cells encounter specific antigens presented by microglia. Of the helper T cells re-stimulated by autoantigens, Th1 cells producing interferon-γ and Th17 cells secreting interleukin-17 play major roles in propagating inflammation, while Th2 cells producing IL-4, and regulatory T cells secreting IL-10 and TGF-β suppress pathological processes. Final demyelination is rendered either by macrophages recruited from the bloodstream across the BBB, or by TNF-α and nitric oxide, which are secreted by Th1 cells and macrophages, and toxic to CNS myelin.
authors.affiliation: Department of Neurology, Kanazawa Medical University.
authors.forename: Makoto
authors.initials: M
authors.lastname: Matsui
mesh_terms: D017951:Antigen Presentation / Q000276:immunology; D015551:Autoimmunity; D001812:Blood-Brain Barrier / Q000276:immunology; D002490:Central Nervous System / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D039041:Integrin alpha4beta1; D018799:Intercellular Adhesion Molecule-1; D008024:Ligands; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1; D008262:Macrophage Activation / Q000276:immunology; D017628:Microglia / Q000276:immunology; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology*; D009186:Myelin Sheath / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1
chemical_list: D016207:Cytokines; D039041:Integrin alpha4beta1; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1