The eight projects that are supported by this program are focused on four general topics: (1)\The roles of cytokines in the activation and suppression of the microbicidal properties of human monocytes and macrophages. Monocytes treated with cytokines produced by antigen-stimulated mononuclear cells from patients with Chagas disease, Legionnaires' disease, and leprosy (tuberculoid type) have been shown to exhibit enhanced microbicidal activity against several intracellular pathogens (e.g., Trypanosoma cruzi, Leishmania donovani, and Legionella pneumophila). (2)\The capacity of mononuclear phagocytes to secrete toxic oxygen intermediates (H2O2, O2-) and bioactive metabolites of arachidonic acid (prostaglandins, leukotrienes). Current studies are directed toward elucidating the mechanisms that control the type and quantity of each of these secretory products produced by mononuclear phagocytes. (3)\Studies of the structures and functions of complement and Fc receptors of mononuclear phagocytes. Two distinct Fc receptors have been identified on mononuclear phagocytes. The first is present on blood monocytes and binds monomeric IgG1. The second, identified by the monoclonal antibody 3G8, is present in small amounts on blood monocytes but shows increased expression as monocytes develop into macrophages. (4)\Isolation and functional characterization of human dendritic cells. Dendritic cells account for less than 1% of blood leucocytes but are the principal stimulators of syngeneic and allogeneic mixed leucocyte reactions. Monoclonal antibodies have been used to separate dendritic cells from monocytes and macrophages. A monoclonal antibody (3C10) has been developed which reacts with most, if not all, monocytes and tissue macrophages. This monoclonal antibody, together with complement, mediates the lysis of all blood monocytes but does not affect dendritic cells. This method has been used to purify dendritic cells from human blood and to confirm that dendritic cells, not monocytes, are essential accessory cells for T-cell stimulation in humans.