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Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The immunopathogenesis of experimental allergic encephalomyelitis (EAE) is reviewed with special focus on the role of central nervous system fibrin deposition in the inflammatory cascade characterizing this autoimmune disease. Among rats sensitized to whole spinal cord or myelin basic protein of either guinea pig or bovine origin, there is a striking degree of concordance of perivascular fibrin deposits and occurrence of clinical paralytic signs. Neither paralytic signs nor fibrin deposition are temporally related to development of perivascular cellular infiltrates. Rats sensitized to neuroantigen and treated with ancrod, a polypeptide derived from the venom of Agkistrodon rhodostoma, develop profound hypofibrinogenemia, have a marked inhibition of fibrin deposition, and often exhibit no paralytic signs whatsoever. In contrast, cellular infiltrates are not demonstrably influenced by ancrod treatment. Activation of the clotting cascade at loci of developing immune injury of nervous tissue appears to result from and lead to increasing neurovascular permeability and accumulation of edema fluid. Distention of the extracellular space in central and peripheral nervous system tissues by edema fluid appears to be directly responsible for clinical abnormalities characterizing EAE in rats. Cellular infiltrates, on the other hand, appear to be an independent immune response to neuroantigenic sensitization.
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PMID:Experimental allergic encephalomyelitis: role of fibrin deposition in immunopathogenesis of inflammation in rats. 6 95

A hyperacute form of experimental autoimmune encephalomyelitis (HEAE) was induced in Lewis rats using small doses (3.2 mug) of guinea pig myelin basic protein as immunogen and B. pertussis vaccine as adjuvant. Myelin basic proteins from species other than guinea pig (rat, man, monkey, pig, ox, rabbit and sheep) induced only ordinary EAE with this adjuvant. HEAE was more readily distinguished from ordinary EAE by clinical criteria (early onset, with a rapid and severe course, and high incidence of cerebral signs and mortality) than by histologic signs which, although characteristic of HEAE. were not pathognomonic for HEAE, HEAE was transferred to x-irradiated syngeneic recipient rats with lymph node cells from appropriately immunized donors. The Brown Norway (BN) strain of rat was found susceptible to induction of ordinary EAE, but not HEAE, using large doses of either rat or guinea pig myelin basic proteins. The unique immunogenicity of the guinea pig basic protein must be due to a different antigenic determinant from the determinant(s) which is shared by rat and guinea pig myelin basic proteins and which without B. pertussis induces ordinary EAE. The adjuvant action of B. pertussis in inducing HEAE in the Lewis rat is most likely mediated through an immunocompetent T lymphocyte.
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PMID:Antigen, host and adjuvant requirements for induction of hyperacute experimental autoimmune encephalomyelitis. 6 74

Bulk-isolated human and bovine oligodendroglia, practically free from myelin, have been used in attempts to elicit an autoimmune response which has been compared with acute experimental allergic encephalomyelitis (EAE). For these experiments, a total of 20 Hartley guinea pigs, 33 Lewis rats and 16 rabbits have been studied. Animals were inoculated with a range of doses of purified preparations of both human and bovine oligodendroglial cells in complete Freund's adjuvant (CFA) and compared with others challenged with whole white matter in CFA. The latter animals all developed clinical and histological signs of experimental allergic encephalomyelitis (EAE) 2-3 weeks post-inoculation. In general, oligodendroglial cells were encephalitogenically less potent than white matter. Guinea pigs were the most susceptible to inoculations of oligodendroglia. In several given human oligodendroglia 14 days earlier, a paraparesis indistinguishable from conventional EAE was seen. Animals receiving bovine cells showed no clinical signs. Histologically, the CNS of afflicted guinea pigs displayed severe inflammation but, in contrast to conventional EAE in the same species, demyelination was rare in the small group of animals tested. After sensitization with oligodendroglia, rats displayed no clinical disease. Histologically, some given human cells had positive evidence of disease while bovine cells in others gave a mild response. Rabbits showed no clinical and very little histological disease. Although more extensive studies are needed to confirm the findings, from the animals studied it appears that (1) variation in response to inocula containing oligodendroglia exists among the species tested, (2) that human oligodendroglia are more potent immunologically than bovine cells, (3) that CNS lesions produced by these cells in guinea pigs, lack a strong demyelinative component and (4) a specific antigen might exist in oligodendrocytes which is distinct from myelin basic protein. The possible reasons underlying our findings are discussed.
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PMID:Studies on the encephalitogenic effects of purified preparations of human and bovine oligodendrocytes. 6 80

Two peptic fragments (residues 37-88 and 43-88) of guinea pig myelin basic protein which are capable of inducing experimental allergic encephalomyelitis in Lewis rats were cleaved to shorter fragments with alpha-protease (Crotalus atrox proteinase, EC 3.4.24.1) and thermolysin (EC 3.4.24.4). The fragments were isolated, purified, and identified by amino acid composition and NH2- and COOH-terminal residues. The time courses of the reactions, monitored by thin layer electrophoresis of the digests, showed that alpha-protease cleaves peptide (43-88) initially at the Pro(71)-Gln(72) bond, and that the product peptides are subsequently attacked at the Arg(63) -Thr(64), Ser(74)-Gln(75), Arg(78)-Ser(79), and Ser(76)-Gln(80) bonds. No significant cleavages occurred at the -Leu, -Val, and -Ala bonds. These results are in striking contrast to those obtained previously by others workers with other peptide substrates, where selective cleavage at hydrophobic residues occurred. Thermolysin was found to attack peptide (37-88) at the Phe(42)-Phe(43) bond very rapidly; the product peptides were subsequently attacked at the His(60)-Ala(61), Ser(38)-Ile(39)-Tyr(67)-Gly(68), and Pro(84)-Val(85) bonds. These cleavages are compatible with the known specificity of this enzyme. Several of the fragments prepared with these two enzymes, peptides (43-71), (61-88), (75-88), and (72-84) have been used in other studies to locate the encephalitogenic site in the parent peptic peptide.
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PMID:Treatment of an encephalitogenic peptide from guinea pig myelin basic protein with alpha-protease and thermolysin. Isolation of fragments and determination of cleavage sites. 6 52

Two amino acid sequences from the same regions of guinea pig and bovine myelin basic protein which induce experimental allergic encephalomyelitis in Lewis rats were synthesized. The sequences of these two regions may be defined by residues 69 to 84 of the bovine basic protein. The encephalitogenic sequence from guinea pig basic protein (peptide S49), H-Gly-Ser-Leu-Pro-Gln-Lys-Ala-Gin-Arg-Pro-Gin-Asp-Glu-Asn-OH, is a much more potent encephalitogen than that of H-Gly-Ser-Leu-Pro-Gln-Lys-Ala-Gln-Gly-His-Arg-Pro-Gln-Asp-Glu-Asn-OH (peptide S8) found in the bovine protein. The primary structures of the two determinants are similar; however, a Gly-His deletion from the guinea pig sequence is noted. Study of the encephalitogenicity of peptide S49, peptide S8, and the parent proteins suggests that the difference in the encephalitogenic potency of the parent proteins in Lewis rats is due to a natural modification in the primary structure of their respective encephalitogenic determinants.
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PMID:Experimental allergic encephalomyelitis in Lewis rats: chemical synthesis of disease-inducing determinant. 6 39

We determined requirements for the induction of immunoregulatory suppressor cells in experimental allergic encephalomyelitis (EAE) in Lewis rats. Pretreatment of rats with myelin basic protein (BP) in incomplete Freund's adjuvant (IFA) stimulates the proliferation of suppressor cells that localize in lymph nodes and spleen (but not thymus) and exert control over the development of clinical EAE. Dosage studies revealed that 3 X 10(7) suppressor cells can adoptively transfer suppression to syngeneic recipients. Transferred unresponsiveness wanes within 3 weeks, indicating that the suppressor cells are short-lived lymphocytes, although actively induced unresponsiveness persists for at least 8 weeks, probably as a result of continual proliferation under the influence of antigen. No evidence was obtained to suggest that antigen carry-over or blocking antibody production accounts for adoptive transfer of unresponsiveness. Suppressor cells apparently act at the inductive phase of the immune response since they had no inhibitory effect on adoptive transfer of disease by effector lymph node cells. Other mechanisms also may play a role in unresponsiveness to EAE, since rats pretreated i.v. with high dosages of soluble BP were temporarily rendered unresponsive, although suppressor cells could not be detected in these animals.
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PMID:Immunoregulation of experimental allergic encephalomyelitis: conditions for induction of suppressor cells and analysis of mechanism. 7 Apr 89

Several parameters of the in vitro lymphocyte proliferative response to myelin basic protein (BP) in Lewis (Le) and Brown Norway (BN) rats were examined. The results demonstrate that BN rats, a strain normally resistant to BP-induced experimental allergic encephalomyelitis, and Le rats, a strain readily susceptible to the disease, have similar patterns of the proliferative response to BP. An important difference, however, is that BN lymphocytes, although responding significantly to BP, are unable to proliferate to the same level as Le lymphocytes. In experiments measuring the lymphocyte response as a function of antigenic stimulus, days of culture, or type of adjuvant used, the BN rat peak response was in general 70% or less of the Le rat peak response. Furthermore, the BN lymphocyte response was reduced when B cells were removed whereas there was no effect in the Le rat. A negative feedback mechanism, possibly suppressor cells, has been suggested to explain these differences.
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PMID:Kinetics of the in vitro lymphocyte response to myelin basic protein in the the Lewis and Brown Norway strains of rat. 7 6

The hemagglutinating antibody responses of Lewis rats with experimental allergic encephalomyelitis (EAE) and of rats rendered unresponsive to this autoimmune disease by pretreatment with myelin basic protein (BP) were compared. Most tolerant animals produced low levels of hemagglutinating antibody. Similarly, most rats with EAE also produced anti-BP antibodies. We were unable to correlate hemagglutinin production or titer with protection against disease. Hemagglutination inhibition (HAI) studies reveal cross-reactivity between rat, guinea pig and bovine BP. HAI studies with BP-derived peptides suggest that at least three distinct antibody-binding determinants exist in the BP molecule, and that individual inbred Lewis rats respond differently with respect to antibody production to these sites.
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PMID:Antibody response to myelin basic protein: comparisons between Lewis rats with experimental allergic encephalomyelitis, and tolerant rats. 7 24

The present study has investigated central nervous system disease in guinea pigs inoculated with emulsions containing purified preparations of bovine oligodendroglia and their fractions isolated with or without trypsinization, whole bovine white matter or myelin basic protein (MBP). The MBP content of the oligodendroglial fractions was determined by radioimmunoassay. It was found that oligodendroglia prepared from trypsinized fresh brain contained minute amounts of MBP and did not induce disease. The corresponding cell fraction from non-trypsinized frozen brain was rich in MBP and induced disease. Bovine white matter and MBP induced typical experimental allergic encephalomyelitis (EAE). The structural preservation of the non-encephalitogenic trypsinized MBP-poor cells was very good and that of the encephalitogenic MBP-rich non-trypsinized cells very poor. It has been concluded that the encephalitogenicity observed was due to MBP, rather than to a specific oligodendroglial antigen.
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PMID:Encephalitogenic properties of purified preparations of bovine oligodendrocytes tested in guinea pigs. 7 47

The expression of chronic relapsing experimental allergic encephalomyelitis in strain 13 guinea pigs was suppressed with a single series of injections of myelin basic protein in incomplete Freund's adjuvant. The suppression appeared permanent, and subsequent rechallenge with central nervous system antigen failed to elicit exacerbations.
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PMID:Suppression of chronic allergic encephalomyelitis: relevance to multiple sclerosis. 7 24


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