Trichophyton sp. are dermatophyte fungi that commonly colonize human skin or nails. Fungi of the genus Aspergillus are widespread in the environment, and some species, especially A. fumigatus, can colonize human respiratory mucosa. Both of these fungi are associated with several different human diseases which are at least in part related to the form of immune responses that they induce. Antigens and allergens derived from T tonsurans and A. fumigatus will be purified and used for skin testing, to measure serum antibodies and to develop monoclonal antibodies. These monoclonal antibodies will be used in further purification of the antigens and to develop immunoassays for measuring these antigens in extracts, human material and the environment. The primary objective will be to define the immune responses to different proteins and in particular to understand the differences between precipitating antibody responses, IgE antibody responses, and delayed hypersensitivity. Preliminary data suggest that two of the proteins, Asp f I (MW 20kd) and Tri t I (MW 30kd), which react with IgE antibodies are not related to precipitating antibodies or DH. Thus it appears likely for each antigen that the different forms of immune responses are at least in part directed against different proteins from the same source. The studies will therefore aim to purify an A. fumigatus protein that gives rise to precipitating antibodies and a T tonsurans protein that gives rise to delayed hypersensitivity. It appears that dose, site of exposure and the nature of the proteins may each be important in the form of immune response. A further objective is to understand the relationship between exposure of these fungi, induction of immune responses and diseases. The research will provide information in relation to two issues: what is the form of exposure to airborne Aspergillus antigen(s), and which colonized individuals should receive antifungal therapy. The clinical studies will focus on: adults with asthma associated with immediate hypersensitivity to Trichophyton; children with cystic fibrosis who are commonly colonized with Aspergillus species; adults with chronic obstructive lung disease; patients with chronic dermatophyte infection; and adults with sinusitis, ABPA and Aspergilloma.
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