The terminal complement components, C3-9, play a significant role in the host's defense against infection. In order to subserve their protective functions, C3-9, must first be activated to their biologically active forms. There are at least two different mechanisms by which C3-9 can be activated, the alternative pathway and the classical pathway. Since the alternative pathway depends little, if any, on antibody for its activation by microorganisms, it presumably is important in natural immunity. Since the classical pathway usually depends on antibody for its activation by microorganisms, it presumably is important in acquired immunity. We plan on investigating four different aspects of the role of C3-9 in the host's defense against infection. First, we plan on studying the binding of C3b to the surface of the pneumococcus. We hope to determine to what surface structure nascent C3b binds, whether or not the capsule enhances or interferes with that binding and the nature of the bond formed. Second, we plan on determining if teichoic acid from the cell wall of Bacillus subtilis is able to activate the alternative pathway and thus determine if the ability to activate the alternative pathway is a general property of teichoic acids. Third, we plan on investigating the mechanism(s) by which C3-9 plays its protective role in Sindbis virus infection. We hope to determine by which pathway Sindbis virus activates C3-9 and in what way the activation of C3-9 aids in the host's defense against this virus. Finally, we plan on determining by which pathway, the classical or alternative, a variety of pathogenic bacteria activate C3-9 in the sera of newborn infants and thus determine the relative role of each pathway in the newborn's host defense against bacterial infection.