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dc.contributor.authorKay, Richard Andrewen
dc.date.accessioned2013-06-26T14:08:43Z
dc.date.available2013-06-26T14:08:43Z
dc.date.issued1987
dc.identifier.other380413
dc.identifier.urihttp://hdl.handle.net/1842/7455
dc.description.abstractThe mucosal regulation of the systemic immune response to cholera toxin was investigated in inbred adult BALB/c mice. Specific systemic humoral immunity to parenterally administered toxin and an immunopurified, formalinised, antigenically cross-reactive toxoid was measured using isotype-specific enzyme-linked immunosorbent assays. Systemic delayed-type hypersensitivity (DTH) was shown to occur under similar experimental conditions by direct skin testing and histological examination of the sites of antigenic challenge. The passive transfer of DTH with sensitised, draining, peripheral lymph node cells and the specific inhibition of the in vitro migration of these cells in the presence of antigen confirmed that systemic cell-mediated immunity had been induced. A single feed of either the toxin or toxoid was able to inhibit the induction of systemic DTH but did not tolerise specific systemic antibody levels. Oral tolerance to these antigens was found to be both antigen-specific and dose-dependant. The induction of tolerance was inhibited by the pretreatment of animals with a single dose of cyclophosphamide two days before feeding. Splenic T lymphocytes, obtained 7 days after feeding, were able to transfer tolerance for systemic 0TH to syngeneic recipients. Cells with similar properties were also present in the mesenteric lymph nodes at 7 days but were not detected in either tissue 3 days after a single feed of antigen. Transferring these cells at various times after the immunisation of recipients revealed that they inhibited the afferent limb of the DTH response. Feeding mice did not suppress mature DTH effector cell function. Oral tolerance for DTH could also be transferred by serum obtained from animals fed one hour previously. This phenomenon could be abrogated by pretreating recipients with cyclophosphamide. The serum tolerogen did not induce the splenic suppressor T cells found earlier. These findings are discussed in the light of present knowledge and the methods used in this project are critically revieweden
dc.language.isoeng
dc.publisherUniversity of Edinburghen
dc.subjectMedicineen
dc.subjectHumanen
dc.subjectanatomyen
dc.titleMucosal regulation of the systemic immune response to cholera toxinen
dc.title.alternativeThe mucosal regulation of the systemic immune response to cholera toxinen
dc.type.qualificationnamePhD Doctor of Philosophyen


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