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Role of Vaccine-Induced IgG in Protection Against Bordetella Pertussis
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| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | Role of Vaccine-Induced IgG in Protection Against Bordetella Pertussis. |
| 개인저자 | Sedegah Masterson, Mary Yaa. |
| 단체저자명 | University of Maryland, Baltimore. Molecular Microbiology and Immunology. |
| 발행사항 | [S.l.]: University of Maryland, Baltimore., 2019. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2019. |
| 형태사항 | 108 p. |
| 기본자료 저록 | Dissertations Abstracts International 80-12B. Dissertation Abstract International |
| ISBN | 9781392301555 |
| 학위논문주기 | Thesis (Ph.D.)--University of Maryland, Baltimore, 2019. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 80-12, Section: B.
Publisher info.: Dissertation/Thesis. Advisor: Pasetti, Marcela F. |
| 이용제한사항 | This item must not be sold to any third party vendors. |
| 요약 | Bordetella pertussis is a highly infectious respiratory pathogen that can induce severe bronchopneumonia and respiratory failure in infants (whooping cough). Vaccine formulations consisting of Diphtheria toxoid, Tetanus toxoid, and Acellular Pertussis (aP) components (DTaP and Tdap) protect against disease. It remains unclear how a parenteral vaccine, which primarily elicits systemic IgG, contributes to protection against a respiratory pathogen. The goal of this study was to investigate mechanisms by which vaccine-induced IgG reaches the respiratory mucosa and contributes to protection against B. pertussis infection. We hypothesized that pertussis-specific systemic IgG is transported from circulation into the airways via the neonatal Fc receptor (FcRn). To test this hypothesis, wild type mice and mice lacking FcRn (FcRn-/-) were immunized with DTaP or passively transferred DTaP-immune serum and challenged with B. pertussis. Post-challenge readouts included kinetics of Pertussis Toxin (PT) IgG in serum and bronchoalveolar lavage fluid (BALf), bacterial load quantification, and histopathology of lung tissues. WT vaccinated mice were able to clear the infection, whereas FcRn-/- vaccinated mice had residual bacterial counts and increased lung inflammation. Passive administration of DTaP-immune sera reduced lung colonization in both WT and FcRn-/- mice. However, FcRn-/- recipients exhibited moderate bronchopneumonia (absent in WT mice). The lower bacterial clearance and exacerbated tissue damage observed in actively and passively immunized FcRn-/- mice was not due to the absence of PT-IgG (or differences in IgG isotype) in BALf. Rather, WT and FcRn-/- mice had similar PT-IgG levels in serum and BALf, suggesting that FcRn-independent mechanisms mediate IgG transport across the lung. PT-IgG progressively increased in BALf of passively immunized FcRn-/- mice post-challenge (along with lung inflammation,) suggesting IgG also diffuses through damaged lung epithelium. We observed that neutrophils from FcRn-/- mice had lower B. pertussis opsonophagocytic capacity as compared to WT. This impairment in IgG-mediated antimicrobial function in the absence of FcRn could explain the increased inflammation in FcRn-/- mice. In conclusion, we have shown that pertussis-specific IgG translocation into the airways appears to be FcRn-independent, and that IgG-mediated B. pertussis neutrophil phagocytosis may contribute to bacterial clearance and tissue preservation post-infection through FcRn interactions. |
| 일반주제명 | Immunology. |
| 언어 | 영어 |
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: 이 자료의 원문은 한국교육학술정보원에서 제공합니다. |
