Allergic bronchopulmonary aspergillosis (ABA) is a hypersensitivity disease of the lung due to sensitivity to aspergillus fumigatus (AF). It results in marked lung damage in patients with bronchial asthma and cystic fibrosis (CF). The long term objectives of this application are to determine the immunoregulatory abnormalities associated with ABA and to characterize the central and local defects that may predispose to the development of ABA. By understanding the basic mechanisms involved in ABA, we hope to more accurately and appropriately intervene in the patient who is predisposed to develop ABA. The first specific aim of this proposal is to produce a rabbit model of ABA. Appropriate immunization will result in production of rabbit IgE and IgG anti-AF antibodies. Asthma will be produced by inhalation of AF extract. This will be followed by inhalation of AF spores. This should produce a condition that more closely simulates the human state and will enable us to study the immunohistopathology of both bronchoalveolar lavage (BAL) cells and lung tissue.
The second aim i s to study the phenotypic and functional characteristics of BAL lymphocytes from ABA patients.
A third aim i s to examine local susceptibility by comparing the ability of sputum from normal, asthmatics, bronchitics, and CF to support the growth of AF.
The fourth aim i s to extend in vitro co-culture experiments to determine the nature and extent of the specific and non- specific suppressor activity already demonstrated by us in ABA and to examine epsilon receptors on T cells and potentiating factors on IgE synthesis. The fifth aim is to continue longitudinal studies in CF and asthmatic patients to determine the immunologic parameters that change with the development and resolution of ABA.
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