A polyalanine peptide with only five native myelin basic protein residues induces autoimmune encephalomyelitis.
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The minimum structural requirements for peptide interactions with major histocompatibility complex (MHC) class II molecules and with T cell receptors (TCRs) were examined. In this report we show that substituting alanines at all but five amino acids in the myelin basic protein (MBP) peptide Ac1-11 does not alter its ability to bind A alpha uA beta u (MHC class II molecules), to stimulate specific T cells and, surprisingly, to induce experimental autoimmune encephalomyelitis (EAE) in (PL/J x SJL/J)F1 mice. Most other amino acid side chains in the Ac1-11 peptide are essentially irrelevant for T cell stimulation and for disease induction. Further analysis revealed that binding to A alpha uA beta u occurred with a peptide that consists mainly of alanines and only three of the original residues of Ac1-11. Moreover, when used as a coimmunogen with MBP Ac1-11, this peptide inhibited EAE. The finding that a specific in vivo response can be generated by a peptide containing only five native residues provides evidence that disease-inducing TCRs recognize only a very short sequence of the MHC-bound peptide. (+info)
Suppression of allergic encephalomyelitis in rats by means of antibrain serum.
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Rats regularly develop evidence of allergic encephalomyelitis (AE) 2 to 3 weeks following sensitization to nervous tissue plus adjuvant. Independent of the severity of AE which occurs, gradual recovery is the rule and by the 6th to 9th week after sensitization rats appear clinically well and microscopic lesions of AE have virtually disappeared. Pooled serum collected from rats 3 or 6 weeks after sensitization contains complement-fixing (CF) antibrain antibodies. Such pooled serum exerts a striking suppressive influence on development of AE when passively administered to rats actively sensitized to nervous tissue. Serum pools which contain CF antibrain antibody suppress the disease. Serum pools lacking CF antibody do not suppress the disease. Serum containing CF antibrain antibody after treatment with 2-mercaptoethanol no longer fixes complement with brain antigen in vitro and no longer suppresses AE in vivo. The data suggest that transfer of protection against AE by passively administered antibrain rat serum is due to an antibrain antibody, possibly the CF antibodies. The meaning of these findings is discussed in terms of the role(s) of circulating antibrain antibody in the pathogenesis of AE. (+info)
Antibody studies in rabbit encephalomyelitis induced by a water-soluble protein fraction of rabbit cord.
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A water-soluble protein fraction of nervous tissue was prepared by extraction of rabbit spinal cord with sodium citrate at pH 4.3. Characterization by nitrogen content and paper electrophoresis showed it to be a mixture of basic proteins. This extract demonstrated encephalitogenic activity when injected into rabbits. The most suitable technique for the measurement of serum antibody to the rabbit cord antigen proved to be the precipitation of antigen-antibody complexes by 40 per cent saturated ammonium sulfate. Antibody could not be demonstrated by the techniques of complement fixation, quantitative precipitation, and Ouchterlony plates. The early appearance of circulating antibody occurred almost exclusively in rabbits that subsequently developed EAE. Specificity of the antibodies for nervous tissue was demonstrated by appropriate blocking and adsorption experiments. (+info)
The expression of the Hu (paraneoplastic encephalomyelitis/sensory neuronopathy) antigen in human normal and tumor tissues.
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Using immunohistochemistry or Western blot analysis, the authors have studied the expression of the Hu antigen (a neuronal protein identified by the serum of patients with small cell lung cancer and paraneoplastic encephalomyelitis/sensory neuronopathy) in normal human tissues and 115 tumors of different histologic types. In normal tissue, the Hu antigen is highly restricted to the nervous system. In lung tumors, the Hu antigen is restricted in its expression to all small cell carcinomas. A few other neuroendocrine-related tumors, especially neuroblastomas (50%), also express the antigen. (+info)
THE APPLICATION OF TISSUE CULTURE TO THE STUDY OF EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS. II. SERUM FACTORS RESPONSIBLE FOR DEMYELINATION.
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1. In the presence of a source of complement, the gamma 2 globulin fraction of rabbit EAE serum results in complete demyelination of myelinated cultures of rat cerebellum. Exposure of the serum to homologous or heterologous brain specifically removes the myelinotoxic activity whereas exposure to non-nervous tissue does not. Polylysine has no effect upon the cultures or upon the demyelinative potency of EAE, whereas heparin inhibits activity presumably through an effect on complement. 2. With the fluorescent antibody technique, the EAE globulins are specifically localized to the myelin sheaths and glial cell membranes during the process of demyelination. As demyelination proceeds, the globulins become localized within the neuroglia in a homogeneous manner which contrasts sharply with the punctate pattern observed in control experiments. 3. The "delayed sensitivity" and classical antibody interpretations of experimental allergic encephalomyelitis are discussed. It is suggested that several factors may be responsible for the pathogenesis of EAE, one of which may well be a myelinotoxic antibody. (+info)
Acute disseminated encephalomyelitis, with massive necrosis of the spinal cord, probably due to antitetanus serum.
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The clinical and pathological findings are described of a fatal case of acute haemorrhagic leucoencephalitis and disseminated encephalomyelitis with acute necrosis of the white matter of the spinal cord. It is suggested that the reaction was a severe immunological response of an allergic nature, probably due to antitetanus serum. (+info)
Rift Valley fever virus-induced encephalomyelitis and hepatitis in calves.
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Three calves (Nos. 1, 2 = 7 days old; No. 3 = 21 days old) were inoculated subcutaneously with virulent Rift Valley fever (RVF) virus. All calves became viremic and clinically ill, but the two 7-day-old calves were moribund and were euthanatized subsequently on post-inoculation day (PID) 3. Highest viral titers were measured in the serum, with lesser concentrations in the brain, heart, spleen, and liver of these animals. Viral antigens were detected by immunohistochemical analysis only in the livers, where positive staining was localized in coalescing foci of hepatocellular necrosis. The 21-day-old calf appeared to recover after viremia and pyrexia but became lethargic and ataxic and was euthanatized on PID 9. The calf was no longer viremic, and RVF virus was isolated only from the brain. Microscopic examination of the central nervous system revealed diffuse perivascular infiltrates of lymphocytes and macrophages, multifocal meningitis, and focal areas of neuronal necrosis and aggregates of macrophages, lymphocytes, and neutrophils throughout all regions of the brain and cervical spinal cord. There was positive immunohistochemical staining for viral antigens within the cytoplasm of neurons and glial cells throughout the central nervous system. Thus, RVF virus can cause encephalomyelitis in calves, and the specific virologic diagnosis can be made by immunohistochemical localization of viral antigens in formalin-fixed tissues. (+info)
Western equine and St. Louis encephalomyelitis.
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In a clinical review of 50 cases of western equine and 16 cases of St. Louis encephalomyelitis in humans it was noted that fever, headache, lethargy, drowsiness, tremor and stiffness of the neck were the most frequent signs or symptoms initiating the illness. The great majority of patients recovered without residual effect. These two diseases of the central nervous system can only be differentiated on an immunological basis but may be suspected during seasonal periods in geographical areas where these virus infections are known to exist. Neuropathological studies were done in four cases of human western equine and two cases of St. Louis encephalomyelitis. The primary point of attack by the virus is the cell body, the lesions being concentrated in the striate body, diencephalon, the brain stem and cerebellum. All histo-anatomical findings (nerve cell destruction, microglial nests, small isolated and confluent areas of necrosis and perivascular round cell infiltration) are secondary to the injury of the nerve cell body caused by the neurotropic virus. (+info)