Molecular and cellular determinants of neuroimmunologic inflammatory disease.
Experimental allergic encephalomyelitis (EAE) and other analogous neuroimmunologic diseases of animals and humans, including multiple sclerosis (MS), are discussed within the context of 1) host lymphoid cells autoreactive with myelin basic protein (MBP) or other neural antigens that elude normal immunoregulatory mechanisms, 2) development of subsets of cytotoxic effector cell clones directed against MBP and other central nervous system (CNS) antigenic components, and 3) neurophysiological and CNS inflammatory structural changes, respectively, which reflect the binding of these effector cell subsets to host CNS target tissue. One set of cytotoxic cells reactive with MBP appears to cause increased permeability of the cerebrovasculature with deposition of fibrin, development of edema, and appearance of clinical paralytic signs of EAE, unaccompanied by infiltrating host inflammatory cells. A second subset of cytotoxic effector cells reactive with non-MBP neural antigen(s) appears to cause the focal, perivascular host inflammatory cell response, which in turn leads to various degrees of demyelination, an important feature of EAE, and the identifying hallmark of the MS process. Indirect evidence, secured by a sensitive radioimmunoassay (RIA), implicates endogenous circulating MBP serum factors (MBP-SFs), characterized by high-affinity binding to anti-MBP antibodies represented in the RIA reagent antiserum, as being of paramount importance in preventing proliferation of neuroreactive cytotoxic lymphoid cells. In this sense MBP-SFs act as neuroautotolerogens. Based on the foregoing concepts and observations, major pathways of CNS injury and inflammation are postulated and discussed.
D000818:Animals; D001921:Brain / Q000098:blood supply; D004679:Encephalomyelitis / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005337:Fibrin / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000276:immunology; D009103:Multiple Sclerosis / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology; D009185:Myelin Proteins / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew
D004676:Myelin Basic Protein; D009185:Myelin Proteins; D005337:Fibrin