A study of non-classical immune interactions with influenza A virus.
Doctoral thesis, UCL (University College London).
The study of the immune system has classically been divided between the innate and the adaptive. Natural antibodies (NAbs) are a class of antibodies produced in response to no well-defined stimuli, with broad-spectrum activity often for conserved carbohydrate antigens. γδ T cells similarly, are a subset of T cells which display oligoclonal T cell receptors specific for conserved microbial antigens. While antibodies and T cells are classically adaptive responses, NAbs and γδ T cells display many non-classical innate interactions. Their interactions with influenza A virus are investigated here with an aim to improve the immune response. Using reverse genetics I have demonstrated here that influenza A viruses can be engineered to express the galα1-3gal and ABO blood group carbohydrate antigens, making them targets for anti-galα1-3gal and anti-ABO antibodies widely expressed in humans. I then investigated the potential of NAbs to enhance the immunity to influenza. In addition, I investigated the presentation of influenza by a novel antigen presenting cell, the γδ T cell. These cells were shown to acquire this antigen by phagocystosis. This surprising capacity for phagocytosis was demonstrated by flow cytometry, by direct observation under confocal and electron microscopy and by functional assays of antigen presentation. γδ T cells could be shown to phagocytose both Escherichia coli and 1μm synthetic beads. This process was at least partly mediated by the receptor for phagocytosis, CD16. Being “adaptive”, γδ T cells retain the capacity for rapid clonal expansion and yet at the same time these cells possess the highly specialized functions of phagocytosis and antigen presentation classically restricted to a small population of innate DCs. Such novel and non-classical immune interactions open new avenues in the development of rapid immunotherapeutic interventions against potential pandemic strains of influenza A.
|Title:||A study of non-classical immune interactions with influenza A virus|
|Additional information:||Authorisation for digitisation not received|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Child Health > Department of Infection and Immunity > ICH - Molecular Immunology Unit|
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