Multiple sclerosis. I. The immune pathogenetic hypothesis.
Animal models indicate that chronic relapsing demyelinating diseases of the central nervous system (CNS) can be induced both by certain viruses and by sensitization to myelinic antigens. Epidemiological data (studies on emigrants and on so-called "Multiple Sclerosis (MS) epidemics") suggest that an environmental transmissible agent, acting on a genetic substrate, could play a role in the pathogenesis of the disease. The transmissible agent could be a virus. Data to this effect are insufficiently indicative, but the hypothesis has been recently put forward that it could be antigenically related to the lymphotropic viruses (HTLV). The transmissible agent could act either by desegregating myelinic antigens or by inducing an alteration of the immune system with a reduction of T lymphocyte suppressor activity. There appears to be rapid and intense activated T lymphocyte "traffic" across the blood-brain barrier in patients affected with MS. Cells specifically sensitized to the unknown antigen find within the CNS other cells able to perpetuate presentation of the antigen (HLA-DR+ astrocytes and endothelial cells, not present in normal brain) and then activate the macrophages which in turn begin immuno-mediated phagocytosis of the healthy myelin. Aspecific immune cells are also recruited into CNS where seem to abnormally proliferate (possibly owing to reduced suppressor activity) producing antibodies against various viral or cerebral antigens which are not clearly related to the pathogenesis of the disease (production of intra-CNS "nonsense" antibodies and synthesis of the oligoclonal immunoglobulin bands seen at the cerebrospinal fluid electrophoresis.)
Bergamini
L
L
Istituto di Clinica delle Malattie del Sistema Nervoso, Università Torino.
Durelli
L
L
D000911:Antibodies, Monoclonal / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D001402:B-Lymphocytes / Q000502:physiology; D005805:Genes, MHC Class I / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007136:Immunoglobulins / Q000134:cerebrospinal fluid; D007372:Interferons / Q000502:physiology; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D011971:Receptors, Immunologic / Q000235:genetics; D013491:Suppressor Factors, Immunologic / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology; D014777:Virus Diseases / Q000150:complications*
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D006680:HLA Antigens; D007074:Immunoglobulin G; D007136:Immunoglobulins; D011971:Receptors, Immunologic; D013491:Suppressor Factors, Immunologic; D007372:Interferons