CELL-MEDIATED IMMUNITY IN ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS

Abstract

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease mediated by an allergic late-phase inflammatory response to Aspergillus fumigatus antigens characterized by markedly elevated allergen specific and total immunoglobulin E (IgE) levels and eosinophilia, and manifested by wheezing, pulmonary infiltrates, and pulmonary bronchiectasis and fibrosis. ABPA afflicts only a small percentage of susceptible atopic individuals with either asthma or cystic fibrosis (CF). ABPA is unique in that it is caused by A. fumigatus, a living fungus growing within the mucosal lumen of the bronchi that releases a multitude of proteins whose biologic function alters the host immune responses in addition to being immunogenic. Elucidation of the immunopathogenesis of ABPA has provided valuable information related to allergen-induced chronic asthma. More recently, immunogenetic studies have further contributed to the understanding of the immunopathogenesis of why certain individuals are susceptible to develop ABPA. Immunologic responses to Aspergillus, as well as to other microorganisms, may be categorized as either T helper (Th)1 or Th2 CD4+ T-cell responses. 61, 110, 128 Th1 CD4+ T-cell cytokines, such as interferon gamma (IFN-γ), interleukin 2 (IL-2), and tumor necrosis factor (TNF)-β, enhance cytotoxic and macrophage activity (e.g., cellular immunity), whereas Th2 CD4+ T-cell cytokines, such as IL-4, IL-5, IL-10, and IL-13, promote antibody synthesis (e.g., humoral antibody immunity) (Table 1). It is hypothesized that protective host immunity to A. fumigatus is a Th1 CD4+ T-cell response, whereas a Th2 CD4+ T-cell humoral response found in ABPA is nonprotective and leads to a hypersensitivity pulmonary lung disease.