Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experimental allergic encephalomyelitis (EAE) is a prototypic neuroautoimmune disease involving sensitization to central nervous system myelin basic protein (MBP). Our studies of the clotting system and ensuing fibrinolysis implicate coagulation and cleavage of fibrin within or on the luminal surface of the cerebrovasculature as events initiating the inflammation characterizing EAE. Among recipient rats injected with MPB-primed, cultured-activated lymph node cells, opening of the blood-brain barrier (BBB) and deposition of perivascular fibrin within the spinal cord occur in parallel 1 day before onset of clinical signs of EAE. Daily treatment of recipient rats with trans-4-(aminomethyl)cyclohexanecarboxylic acid, a synthetic product that specifically inhibits plasminogen activator derived from endothelial cells, results in marked reduction of increased permeability of the BBB and suppression of clinical signs of EAE. We postulate that the critical event precipitating EAE is binding of circulating MBP-reactive immune effector cells to MBP immunodeterminants on the surface of cerebrovascular endothelial cells. Coagulation and ensuing fibrinolysis occur at sites of binding of effector cells to cerebrovascular endothelium. Release of biologically active peptides cleaved from fibrin open the BBB, thereby setting the stage for the cascade of inflammatory events culminating in clinical manifestations of EAE.
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PMID:Role of the clotting system in the pathogenesis of neuroimmunologic disease. 243 64

Indirect evidence suggests that an autoimmune response to myelin basic protein (MBP) may be involved in the pathogenesis of multiple sclerosis (MS). In MS, several reports have suggested that restricted T-cell populations respond to MPB, as in inbred rodents with the MS disease model experimental allergic encephalomyelitis. In experimental allergic encephalomyelitis, the T-cell repertoire to MBP varies between strains, and in MS it is likely that the response to MBP is also best defined under conditions where genetic differences between subjects are controlled. In this report, the fine specificity of the T-cell response to MBP was assessed in three families, each with multiple individuals affected with MS. We found that (1) comparable frequencies of MBP-reactive T-cell lines were obtained from peripheral blood of MS patients and their healthy siblings. Human leukocyte antigen (HLA) identical sibling pairs discordant for MS had similar frequencies of MBP-reactive T-cell lines. (2) A broad spectrum of MBP epitopes was recognized by T-cell lines from all individuals studied. Within a family, the fine specificity of MBP recognition showed little or no overlap between individuals, even between HLA identical siblings. (3) Recognition of MBP epitopes occurred in the context of different HLA class II alleles. At least four DR alleles each served as restricting elements for recognition of P82-101 or the carboxy terminal region of MBP, two regions thought to be important in the human T-cell response to the molecule. No relationship between the use of a particular DR allele and a response to a particular region of MBP could be established.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The T-cell response to myelin basic protein in familial multiple sclerosis: diversity of fine specificity, restricting elements, and T-cell receptor usage. 768 20

Intrathymic injection of guinea pig myelin basic protein (MBP) or the immunodominant, encephalitogenic fragment of MPB, 68-86, without otherwise compromising the peripheral lymphocyte pool in adult LEW rats, dramatically inhibits onset of experimental allergic encephalomyelitis (EAE) caused by the usual peripheral inoculation with MBP in complete Freund's adjuvant. This surprising finding demonstrates that interaction of antigen and one or more components of an intact thymus can down-regulate systemic responses by mature T cells already existing in the peripheral lymphocyte pool. How this happens is not known. In studies designed to explore possible mechanisms: (a) adult thymectomized animals remain susceptible to active EAE, thus EAE cannot be attributed solely to recent thymic emigrants that might be inactivated by antigen deposited in the thymus; (b) heterotopic isografts of injected thymic lobes transfer thymic tolerance to secondary recipients, thus the tolerance effect is dominant over an intact, non-treated thymus; (c) T cells from made thymic tolerant but not immunized donors are less effective in causing EAE following adoptive transfer into, and active immunization of, secondary, irradiated recipients; and (d) animals resistant to active EAE as a consequence of thymic tolerance are fully vulnerable to adoptive EAE caused by already activated MBP-specific T cell subpopulations. These results rule out a possible mechanism previously proposed for acquired thymic tolerance, i. e., that potentially pathogenic T cells traffic to the antigen-injected thymus where they are inactivated or eliminated.
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PMID:Acquired thymic tolerance and experimental allergic encephalomyelitis in the rat. I. Parameters and analysis of possible mechanisms. 975 64