The Roles of IFN-y and IL-4 in the Upper and Lower Respiratory Tracts Immune Responses Toward Mycoplasma Infection
dc.contributor.advisor | Jerry Simecka | |
dc.creator | Woolard, Matthew D. | |
dc.date.accessioned | 2019-08-22T20:05:17Z | |
dc.date.available | 2019-08-22T20:05:17Z | |
dc.date.issued | 2003-12-01 | |
dc.date.submitted | 2013-11-15T14:00:28-08:00 | |
dc.description.abstract | Woolard, 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.mimetype | application/pdf | |
dc.identifier.uri | https://hdl.handle.net/20.500.12503/27758 | |
dc.language.iso | en | |
dc.provenance.legacyDownloads | 0 | |
dc.subject | Medical Cell Biology | |
dc.subject | Medical Physiology | |
dc.subject | Medical Sciences | |
dc.subject | Medical Specialties | |
dc.subject | Medicine and Health Sciences | |
dc.subject | Rheumatology | |
dc.subject | Respiratory Tracts | |
dc.subject | immune | |
dc.subject | immune responses | |
dc.subject | infection | |
dc.subject | mycoplasma | |
dc.title | The Roles of IFN-y and IL-4 in the Upper and Lower Respiratory Tracts Immune Responses Toward Mycoplasma Infection | |
dc.type | Dissertation | |
dc.type.material | text | |
thesis.degree.department | Graduate School of Biomedical Sciences | |
thesis.degree.grantor | University of North Texas Health Science Center at Fort Worth | |
thesis.degree.name | Doctor of Philosophy |
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