The Roles of IFN-y and IL-4 in the Upper and Lower Respiratory Tracts Immune Responses Toward Mycoplasma Infection

dc.contributor.advisorJerry Simecka
dc.creatorWoolard, Matthew D.
dc.date.accessioned2019-08-22T20:05:17Z
dc.date.available2019-08-22T20:05:17Z
dc.date.issued2003-12-01
dc.date.submitted2013-11-15T14:00:28-08:00
dc.description.abstractWoolard, Matthew D., The Roles of IFN-γ and IL-4 in the Upper and Lower Respiratory Tracts Immune Responses Toward Mycoplasma Infection. Doctor of Philosophy (Biomedical Sciences), December, 2003, 136 pp., 1 table, 16 illustrations, bibliography, 152 titles. The purpose of these studies was to evaluate the roles of IFN-γ and IL-4 during the development of immune responses of the upper and lower respiratory tracts, during mycoplasma respiratory disease. To study their roles, we took advantage of IFN-γ and IL-4 knockout (KO) mice. The loss of IL-4 did not impact the development of disease or the clearance of mycoplasma from either respiratory tracts during mycoplasma infection. However, IL-4 mediated responses dampen mycoplasma induced bronchial hyperresponsiveness (BHR), which are in direct contrast to theories that state that IL-4 is critical for the development of BHR. This suggests that mycoplasma exacerbation of asthma is a synergism between IL-4 and non-IL-4 mediated responses. Thus, IL-4 does not impact mycoplasma disease development, but dampens detrimental non-IL-4 mediated responses that exacerbate BHR during mycoplasma disease. The loss of IFN-γ did not affect disease or the number of mycoplasma organisms in the upper respiratory tract; this is in contrast to the lungs where the loss of IFN-γ led to a defect in innate immune responses. A significant increase in mycoplasma organisms were seen by day 3 post-infection which led to exacerbation of disease pathology. By three days after infection, only the number of IFN-γ+ NK cells increase in numbers in response to mycoplasma infection. However, the depletion NK cells by anti-asialo GM1 antibody treatment did not affect the clearance of mycoplasma from lungs of BALB/c mice, however, NK cell depletion from IFN-γ KO mice lead to increased clearance of mycoplasma organisms from the lung. Further studies demonstrated that NK cells in an IFN-γ deficient environment lead to increased secretion of IL-10, G-CSF, and TNF-α and increased numbers of cell infiltrated into the alveoli and airways. These results suggest that NK cells of the lung have anti-inflammatory roles that IFN-γ counteracts in BALB/c mice. Regardless, these studies demonstrate that NK cells in an IFN-γ deficient environment impair innate immune responses from clearing mycoplasma organisms from the lung. These studies demonstrated diverse but novel functions for IFN-γ and IL-4 during respiratory infections that will have significant impact on future studies of respiratory immunology.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/20.500.12503/27758
dc.language.isoen
dc.provenance.legacyDownloads0
dc.subjectMedical Cell Biology
dc.subjectMedical Physiology
dc.subjectMedical Sciences
dc.subjectMedical Specialties
dc.subjectMedicine and Health Sciences
dc.subjectRheumatology
dc.subjectRespiratory Tracts
dc.subjectimmune
dc.subjectimmune responses
dc.subjectinfection
dc.subjectmycoplasma
dc.titleThe Roles of IFN-y and IL-4 in the Upper and Lower Respiratory Tracts Immune Responses Toward Mycoplasma Infection
dc.typeDissertation
dc.type.materialtext
thesis.degree.departmentGraduate School of Biomedical Sciences
thesis.degree.grantorUniversity of North Texas Health Science Center at Fort Worth
thesis.degree.nameDoctor of Philosophy

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