the details of interactions between exposure and host factors remain. The literature of CBD is extensive, and this section consists of a selective review of the primary pertinent literature that has shaped current understanding of the immune mechanisms involved and of genetic factors that might contribute to susceptibility to the disease.
CBD is a systemic granulomatous disorder that affects the lungs predominantly. The mechanism underlying CBD pathogenesis involves an immune response to beryllium (Figure 4-1). CD4+ T lymphocytes recognize beryllium as an antigen that triggers cell proliferation and release of cytokines and inflammatory mediators. The release of inflammatory mediators results in an accumulation of mononuclear-cell infiltrates and fibrosis that lead to the lesion typical of the disease—a noncaseating granuloma.
Beryllium acts as a major histocompatability complex (MHC) class II restricted antigen that stimulates the proliferation and accumulation of beryllium-specific CD4+ T cells in the lungs (Saltini et al. 1989, 1990). Two observations illustrate the primary importance of CD4+ T cells in the pathogenesis of CBD: the development of granulomatous inflammation in the lungs is associated with the accumulation of CD4+ T cells in bronchoalveolar-lavage (BAL) fluid, and sensitization to beryllium is detected in the ability of CD4+ T cells to proliferate in response to beryllium salts in culture.