B-Cell Response to Viruses that Infect the Respiratory Tract
Virus-specific antibodies play a key role in providing a protective barrier to infection and in facilitating viral clearance once an infection is established. Antibody-producing cells or plasma cells are generated from B cells that divide and differentiate following recognition of specific antigen.
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Determinants of Heterosubtypic Immunity to Influenza
This project is focused on identifying the specificities of T cell responses to influenza in both animal models and in humans. Although humans possess immune responses that cross-react against different subtypes of influenza (so-called heterosubtypic immunity), there is little evidence of its specificity, and the reasons why it may or may not be protective are unclear.
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Imaging of T Cell Trafficking in a Mouse Model of Influenza Tracheitis
Influenza virus targets the epithelial lining of the respiratory tract. Cytotoxic CD8 T cells that leave the circulation and infiltrate the airway epithelium play a key role in controlling infection. However, little is known about mechanisms of T cell migration in the airway environment and engagement with infected epithelial cells. To investigate these processes, our lab has developed a mouse model of influenza tracheitis and used live imaging techniques to follow the tissue trafficking of infiltrating, virus-specific T cells. Ongoing studies are aimed at understanding molecular interactions that regulate this process.
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Immune Responses to the 2009 Pandemic H1N1 Virus
As part of our investigations into immune protection from influenza, we have developed a series of related research projects focused on understanding how immune responses to the novel H1N1 influenza virus that emerged in 2009 (pH1N1) to cause a worldwide pandemic. In human subjects, we are investigating pre-existing immunity that cross-reacts with the pH1N1 virus.
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Mathematical and Computational Modeling of Influenza Immunity
Mathematical and computational methods are being employed to model aspects of the immune response to influenza. The goal of the CBIM is to develop comprehensive, quantitative models of the immune response to influenza A infection, a potential bioterror agent and emerging pathogen, and create computational tools to explore such scenarios in silico.
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Dynamics of CD8 T Cell Migration in the Influenza-infected Airways Leading to Establishment of Tissue Resident Memory
Influenza virus infects the epithelial cells that line the respiratory tract. Productive replication of the virus is restricted to this site because of the requirement for a locally expressed trypsin-like enzyme to cleave nascent viral hemagglutinin (HA) surface protein into its active conformation.
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The Pivotal Role of VLA-1 in T Cell Immunity to Influenza
Optimal T cell mediated immunity to virus infection of peripheral tissues depends on the ability of the T cells to home to, function, and be retained in these sites. Because of the diversity in the structure and function of peripheral organs, a mechanism to regulate T cells in different organs must involve components shared by many tissues. A feature common to many tissues is the presence of extracellular matrix. Collagen IV is uniquely found in the basement membranes that form the foundation for all epithelial and endothelial surfaces.
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Analysis of Viral Genes and Host Responses Influencing the Severity of Influenza Virus and Respiratory Syncytial Virus Infection
Viral proteins and host cell responses are key determinants of the severity of viral infections of the respiratory tract. To identify viral genes and mutations that influence the severity of influenza virus and respiratory syncytial virus (RSV) infections, we are isolating and sequencing these viruses from subjects experiencing mild or severe disease.
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Analysis of Host Responses to Respiratory Syncytial Virus Infection and Identification of Factors Associated with Severe Disease
Respiratory syncytial virus (RSV) infects about 70% of infants during their first winter. Most infections are mild, but 1-3% result in hospitalization. There is evidence that T cells play a role in the severity of RSV-induced disease, but mechanisms are not well understood.
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T Cell Function in Preterm Infants
Infants delivered preterm (prior to 37 weeks gestation) are at high risk for severe disease from viral respiratory infections. It is unknown if premature delivery alters T cell function in a way that increases susceptibility to viral infection or immunopathology. It is also unknown how premature antigen exposure affects the composition of the circulating T cell pool.
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