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Reovirus 1/L and influenza A infection of the upper and lower respiratory tracts: A paradigm for studies of the respiratory tract in the context of mucosal immunity

Posted on:1999-05-11Degree:Ph.DType:Dissertation
University:Medical University of South CarolinaCandidate:Thompson, Amy HodsonFull Text:PDF
GTID:1464390014471267Subject:Immunology
Abstract/Summary:
Models exist to study immune mechanisms of the respiratory tract, however they have not allowed analysis of the interaction of the lower respiratory tract with other components of the mucosal immune system. Reovirus 1/L, an effective gut mucosal immunogen is also a natural respiratory mucosal immunogen. Reovirus 1/Lang infection of the lower respiratory tract generated a severe viral bronchopneumonia characterized by an inflammatory cellular infiltrate in the lung interstitium and alveolar spaces. B lymphocytes capable of generating reovirus-specific antibody responses, cytotoxic effector cells capable of lysing reovirus-infected cells, and T lymphocyte populations which predominantly produced IL-2 and IFN-gamma were generated following i.n. infection. The cytokine production patterns observed in vivo after reovirus infection did not correlate with classical T cell cytokine expression patterns, instead, the presence of multiple types of lymphocyte populations capable of producing one of several possible cytokine combinations, with the potential of performing separate functions in the response to and resolution of infection was demonstrated.;The GCT antigen, a germinal center B-cell and CD8 T-cell marker, was present on 21--60% of the inflammatory lymphocytes in the lung following i.n. infection with reovirus. A novel population of GCT-expressing CD4 + lymphocytes unique to reovirus-stimulated lung alveolar and interstitial lymphocyte populations was identified.;Studies of the organized lymphoid tissue of the upper respiratory tract, nasal associated lymphoid tissue (NALT), demonstrated that murine NALT is capable of generating specific anti body-forming cells (AFCs) in response to upper respiratory tract infection with either reovirus 1/L or influenza type A. IgM AFC responses were induced in NALT cell cultures from uninfected mice following in vitro culture with influenza virus, therefore a part of the AFCs in infected mice may have originated from specific B cell precursors in the NALT. NALT lymphocytes from influenza A (PR8) infected mice produced IFN-gamma but not IL-4 when cultured for 24 hours. Infection of both the upper and lower respiratory tract with reovirus generated a specific AFC response of a much higher magnitude both locally and in other mucosal sites than infection of the upper respiratory tract alone. This suggests that stimulation of the NALT alone does not induce optimal respiratory protection, and that immunization of the lower respiratory tract in addition to the upper respiratory tract could increase the efficacy of vaccines designed to induce local immunity.
Keywords/Search Tags:Respiratory tract, Reovirus 1/L, Infection, Mucosal, Influenza
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