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dc.contributor.advisorZaghouani, Habibeng
dc.contributor.authorHoeman, Christineeng
dc.date.issued2012eng
dc.date.submitted2012 Falleng
dc.descriptionTitle from PDF of title page (University of Missouri--Columbia, viewed on March 11, 2013).eng
dc.descriptionThe entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file.eng
dc.descriptionDissertation advisor: Dr. Habib Zaghouanieng
dc.descriptionIncludes bibliographical references.eng
dc.descriptionVita.eng
dc.descriptionPh. D. University of Missouri-Columbia 2012.eng
dc.description"December 2012"eng
dc.description.abstract[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Newborns are highly susceptible to microbial infections and allergic reactions. This susceptibility is due to a lack of Th1 cells and an excess of Th2 cells. However, the mechanism underlying this Th1/Th2 imbalance has not been clearly elucidated. Although Th1 cells are present in the primary response, they up-regulate the IL-13R[alpha]1 chain. Consequently, IL-13R[alpha]1 can bind with IL-4R[alpha] to form a heteroreceptor through which IL-4 from Th2 cells can signal and cause the death of Th1 cells. Formation of this death receptor is influenced by the neonatal environment and intrinsic T cell factors. Here we show that limited IL12 in the neonatal environment supports IL-13Ralpha1 up-regulation and Th1 cell death. This lack of IL-12 is due to a low frequency of CD8[alpha]+CD4- DCs, the main producer of IL-12. However, by day 6 after birth, this DC subset reaches a significant accumulation and produces sufficient IL-12 that can downregulate IL-13R[alpha]1 and restore Th1 responses. Interestingly, T cells also contribute to the Th2 bias of neonatal immunity as adult T cells do not up-regulate IL-13Ralpha1 when primed within the neonatal environment. In fact, by 8 days after birth T cells do not up-regulate IL-13R[alpha]1 after antigen stimulation as they express the IL-12R[beta]2 chain which serves as a compensation mechanism that prevents death. Finally, IL-4 induced death appears to be due to activation of the extrinsic and intrinsic apoptosis pathways as neonatal Th1 cells have increased FasL and Bim expression. Together these results could have direct impact on pediatric vaccine development.--From public.pdfeng
dc.description.bibrefIncludes bibliographical references.eng
dc.format.extentx, 164 pageseng
dc.identifier.oclc852513304eng
dc.identifier.urihttps://hdl.handle.net/10355/33190
dc.identifier.urihttps://doi.org/10.32469/10355/33190eng
dc.languageEnglisheng
dc.publisherUniversity of Missouri--Columbiaeng
dc.relation.ispartofcommunityUniversity of Missouri-Columbia. Graduate School. Theses and Dissertationseng
dc.rightsAccess is limited to the campus of the University of Missouri--Columbia.eng
dc.subjectneonatal immunityeng
dc.subjectpediatric vaccineseng
dc.subjectTh2 responseeng
dc.titleDendritic cells, IL-12Rbeta2, and IL-13Ralpha1 signaling: the battle for control of neonatal immunityeng
dc.typeThesiseng
thesis.degree.disciplineMicrobiology (Medicine) (MU)eng
thesis.degree.grantorUniversity of Missouri--Columbiaeng
thesis.degree.levelDoctoraleng
thesis.degree.namePh. D.eng


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