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dc.contributor.authorHayes, Tristan Alonzoen
dc.date.accessioned2018-10-18T06:00:57Zen
dc.date.available2018-10-18T06:00:57Zen
dc.date.issued2017-04-25en
dc.identifier.othervt_gsexam:10741en
dc.identifier.urihttp://hdl.handle.net/10919/85399en
dc.description.abstractAllergic airway diseases such as rhinitis, asthma, and chronic rhinosinusitis are responsible for causing a huge economic burden on patients and society. Patients suffering from asthma often have allergies to pollen, dust mite, and mold. Interestingly, studies have shown that there is a correlation between severe asthma and sensitization to fungi including Aspergillus, Alternaria, Cladosporium, and Penicillium. This project has been focused on studying the innate immunomodulatory activities of the major allergen Alt a 1, from the ubiquitous airborne fungus, Alternaria alternata. In several studies, 90-100% of allergic patients who are sensitized to Alternaria, have Alt a 1 specific IgE antibodies indicating that it is a major and clinically relevant allergen. Although progress has been made over the past few decades regarding elucidating the mechanistic underpinnings of allergic inflammation, more research needs to be done, especially in regards to innate immunity and its role in the sensitization and exacerbation aspects of allergic diseases. Published studies have increasingly made it clear that Toll-like receptors (TLRs) are key players in innate immunity to several allergens. For example, the dust mite allergen, Der p 2, has been shown to mimic the activity of human and mouse MD2 in the presence of LPS to trigger a response through TLR4. Bet v 1, an allergen from Birch tree, has been shown to enter and be transported through lung epithelium in patient cells. It is hypothesized that transcytosis of allergens like Bet v 1 may contribute to sensitization and exacerbation in atopic individuals. This project was focused on two primary aims; (1) Characterize the innate immune response of Alt a 1 in human airway epithelial cells, and (2) Identify if and how Alt a 1 can enter human airway cells. We found that Alt a 1 was able to stimulate innate immune responses in bronchial epithelial cells and this was dependent upon TLR2, TLR4 and the downstream adaptor proteins MyD88 and TIRAP. We also found in our studies that Alt a 1 rapidly enters bronchial epithelial cells. Furthermore, our data suggests that endocytosis of Alt a 1 may be partially dependent upon interaction with phosphatidyl-inositol-3-phosphate (PI-3-P).en
dc.format.mediumETDen
dc.publisherVirginia Techen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectallergenen
dc.subjectallergyen
dc.subjectAlternariaen
dc.subjectAlt a 1en
dc.subjectasthmaen
dc.subjectendocytosisen
dc.subjectinnate immunityen
dc.subjectprotein-lipid interactionsen
dc.titleCharacterizing the Innate Immune Response of Human Airway Cells to the Unique Fungal Allergen Alt a 1en
dc.typeDissertationen
dc.contributor.departmentBiological Sciencesen
dc.description.degreePh. D.en
thesis.degree.namePh. D.en
thesis.degree.leveldoctoralen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.disciplineBiological Sciencesen
dc.contributor.committeechairLawrence, Christopher B.en
dc.contributor.committeememberLi, Liwuen
dc.contributor.committeememberSchubot, Florian D.en
dc.contributor.committeememberKale, Shiv D.en
dc.contributor.committeememberCapelluto, Daniel G.en


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