Figure 1.

Immunopathogenesis of chronic beryllium disease and sarcoidosis. In CBD (A), beryllium particles enter the lung and generate an immune response. In sarcoidosis (B) unknown antigens induce an immune response after entering the lung. In CBD, beryllium particles cause the release of DAMPs in the airways, which promote activation and migration of DCs. Either beryllium (A) or unknown antigens (B) are taken up by alveolar macrophages and dendritic cells in the lung and are transported to lung-draining lymph nodes. In the lymph nodes, antigen specific CD4+ T cells are stimulated by activated antigen-presenting cells expressing certain HLA molecules dependent on disease (see Table 1). T-B cell interactions also occur in the lymph nodes and commitment of B cells to antibody production takes place in the germinal centers. Antibodies and activated B and T cells circulate back to the lung to generate an adaptive immune response against the target antigen. In CBD, Th1 CD4+ T cells that display an effector memory phenotype are the primary cell type, but there is also an infiltration of activated B cells in the lungs that help form granulomatous structures (A). In sarcoidosis and CBD, Th1 CD4+ T cells make up the majority of the cell population in the lungs. In sarcoidosis, but not CBD, there are also Th17 and Th17.1 cells present. SAAs are also present in pulmonary granulomas of sarcoidosis patients, but not CBD, where they contribute to the inflammatory milieu and induce proliferation of pathogenic, inflammatory Th17 cells. In both diseases, there is an abundance of Th1 inflammatory cytokines secreted by T cells and innate cells that propagate the inflammatory environment, including TNF-α, IFN-γ, IL-1, and IL-2.