Immune and Inflammatory Responses Differ Between the Upper and Lower Respiratory Tract

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dc.contributor.advisorSimecka, Jerry
dc.contributor.committeeMemberGoldfarb, Ronald H.
dc.contributor.committeeMemberMathew, Porunelloor A.
dc.creatorHodge, Lisa M.
dc.date.accessioned2019-08-22T21:05:57Z
dc.date.available2019-08-22T21:05:57Z
dc.date.issued2001-05-01
dc.date.submitted2013-07-23T11:00:11-07:00
dc.description.abstractThe purpose of these studies was to evaluate the role of upper and lower respiratory immune responses during immunization against respiratory disease antigens, and to characterize which immune responses during immunization against respiratory disease antigens, and to characterize which immune responses contribute to protection in the respiratory tract during infection. After nasal immunization, antigen-specific IgA antibody forming cells dominated throughout the respiratory tract. However, IgG responses were significant in lungs, but not in nasal passages. Furthermore, parental immunization did not enhance humoral immunity in the upper respiratory tract even after a nasal challenge, whereas extrapulmonary lymphoid responses enhanced responses in the lung. After nasal immunization, inflammatory reactions developed within the lungs of mice, but not in nasal passages. Lowering dosages of CT reduced, but did not eliminate, these adverse reactions without compromising immunogenicity. Serum IgE responses were also enhanced in a dose dependent manner by inclusion of CT. During infection, mRNA expression for IL-4 was greater in the nasal passages, while both mRNAs for IL-4 and IFN-y were increased in the lungs. As well, we found increased mycoplasma organisms in the lungs of IFN-y-/- mice, suggesting a protective role for cell-mediated immunity in the lung. In contrast, IL-4-/- mice had greater mycoplasma organisms in the nasal passages, indicating IL-4 responses are crucial for upper respiratory tract protection. Consistent with antigen deposition, nasal inoculation with 10 μl volume of antigen plus CT resulted in significant IgA responses in the nasal passages compared to mice given 24 μl immunizations; however, lower respiratory tract immunizations generated antibody responses in both nasal passages and lungs. In addition, both immunizations resulted in equivalent serum antibody responses. Upper and total respiratory tract immunizations provided protection in the nasal passages when CT was added. However, in the lung, all immunizations resulted in protection against mycoplasma infection, regardless of the inclusion of CT, suggesting a different role for CT as an adjuvant in upper and lower respiratory tract immune protection. In conclusion, we found immune responses generated during immunization and infection are different between the upper and lower respiratory tracts, and the contribution of these responses to clearance of respiratory infection differs.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/20.500.12503/29066
dc.language.isoen
dc.provenance.legacyDownloads0
dc.subjectCirculatory and Respiratory Physiology
dc.subjectHealth Services Research
dc.subjectImmunity
dc.subjectImmunology of Infectious Disease
dc.subjectImmunopathology
dc.subjectLife Sciences
dc.subjectMedical Immunology
dc.subjectMedicine and Health Sciences
dc.subjectOther Immunology and Infectious Disease
dc.subjectOtolaryngology
dc.subjectRespiratory System
dc.subjectRespiratory Tract Diseases
dc.subjectUpper respiratory immune responses
dc.subjectlower respiratory immune responses
dc.subjectimmunization
dc.subjectrespiratory disease antigens
dc.subjectantigen specific IgA antibody
dc.titleImmune and Inflammatory Responses Differ Between the Upper and Lower Respiratory Tract
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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