Show simple item record

dc.contributor.authorMulder, Daniel Jeremy
dc.contributor.otherQueen's University (Kingston, Ont.). Theses (Queen's University (Kingston, Ont.))en
dc.date2011-06-27 14:07:03.348en
dc.date.accessioned2011-06-27T20:19:34Z
dc.date.available2012-11-04T09:00:10Z
dc.date.issued2011-06-27
dc.identifier.urihttp://hdl.handle.net/1974/6576
dc.descriptionThesis (Ph.D, Anatomy & Cell Biology) -- Queen's University, 2011-06-27 14:07:03.348en
dc.description.abstractRecently, a chronic idiopathic disease of the esophagus has emerged, which is now known as eosinophilic esophagitis (EoE). Incomplete knowledge regarding the pathogenesis of EoE has limited treatment options. EoE is known to be a Th2-type immune-mediated disorder. Based on previous studies in both patients and experimental models, it is possible that an abnormal reaction to antigen mediates the pathophysiology of EoE. In this thesis, symptoms and signs unique to EoE were identified by an age-matched, case-controlled study of 326 patients with EoE and gastroesophageal reflux disease. The molecular mechanisms involved in antigen detection in the esophagus, in relation to EoE were then investigated. Esophageal epithelial cells were found, for the first time, to be capable of acting as non-professional antigen presenting cells, with the ability to engulf, process and present antigen on MHC class II to T helper lymphocytes. Antigen presentation by esophageal epithelial cells was induced by interferon-γ, which is increased in biopsies from patients with EoE. Next, it was discovered that esophageal epithelial cell lines expressed functional toll-like receptor (TLR) 2 and TLR3, but in esophageal mucosal biopsies only infiltrating immune cells (including eosinophils) expressed TLR2 and TLR3. Finally, the potential involvement of IgE in the pathogenesis of esophageal inflammation was investigated. IgE in the esophagus was found to be present on mast cells, which are increased in density in the esophageal mucosae of patients with EoE and especially those with a history of atopy. Mechanisms of antigen detection may mediate the pathophysiology of EoE in the esophagus through antigen presentation by epithelial cells, detection by TLRs on immune cells and detection through IgE on mucosal mast cells. Together, these findings demonstrate that mechanisms of antigen detection may actually contribute to the pathophysiology of EoE. Through increased understanding of the mechanisms of EoE, the results of this thesis may contribute to future therapy.en_US
dc.languageenen
dc.language.isoenen_US
dc.relation.ispartofseriesCanadian thesesen
dc.rightsThis publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.en
dc.subjectPathologyen_US
dc.subjectImmunologyen_US
dc.titleThe Pathophysiology of Eosinophilic Esophagitis: Altered Mechanisms of Antigen Detection in the Esophagusen_US
dc.typeThesisen_US
dc.description.restricted-thesisNot all of this thesis is published yet and journals may refuse to publish if they find the pdf of my thesis online. When all of my thesis is published, we will remove the restriction.en
dc.description.degreePh.Den
dc.contributor.supervisorJustinich, Christopheren
dc.contributor.departmentAnatomy and Cell Biologyen
dc.embargo.terms1825en


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record