Host mechanisms of spirochetal killing. Complement-mediated lysis of the organism may be the first line of host defense. Spirochetal lipoproteins and other spirochetal signals activate macrophages, leading to the production of strong proinflammatory cytokines, especially TNF-α and IL-1β. Macrophages engulf spirochetes and degrade them in intracellular compartments. Spirochetal lipoproteins, which are B cell mitogens, also stimulate adaptive T cell–independent B cell responses. Humoral immune responses to nonlipidated spirochetal proteins are more likely to be T cell dependent. The primary role of B. burgdorferi–specific CD4+ Th1 cells is to prime T cell–dependent B cell responses, and antigen-specific CD8+ T cells may be a significant source of IFN-γ. Antibody-mediated spirochetal killing occurs by complement fixation and opsonization.