The proposed investigation will identify factors present in serum of hyperimmunized mice which protect iron-treated animals against infection with virulent Salmonella typhimurium. Although, immune serum by itself exerts no antibacterial activity, it protects iron-treated normal mice if administered before or at the time of infection but not after the infection. This passive transfer of iron-resistant immunity indicates that protective factors of immune serum exert their antibacterial effect through the activity of normal phagocytic cells. In proposed investigation protective factors of immune serum will be separated and purified by various methods; the degree of their protection for normal mice or for tissue cultured macrophages will be measured by determining bacterial multiplication in tissues of infected mice and in infected phagocytes. Cells responsible for the production of protective factors will be identified and the production of protective material will be stimulated by specific antigens and mitogens. The ability of immune factors to transform bacterial growth-supporting macrophage into a bactericidal cell will be investigated in tissue cultures of purified peritoneal macrophages. Untreated and transformed macrophages, maintained in the presence and absence of iron, will be infected with untreated and antibody-coated bacteria; in some experiments, the activity of antibody in the antibody-dependent cellular immunity will be determined by the use of antibodies produced against virulent and avirulent bacteria and their Fc-depleted fragments. In distinction to antibody-independent cellular immunity, which can be neutralized with iron, the antibody-dependent cellular immunity may offer a new method for the production of an effective immunity to Salmonella typhimurium and, probably, to other facultative intracellular parasites. This investigation may provide, also, more information about the mechanism responsible for the antibody-dependent cellular cytotoxicity which is of particular interest in tumor immunology.
