Physiologic role of the complement system in host defense, disease, and malnutrition.

The role of the complement system as a system merging early-phase innate immunity with later-phase acquired immunity has been established. C3 is a key protein of the complement system. It is activated in four pathways: (1) the alternative pathway, (2) the mannan binding protein pathway, (3) the C-reactive protein pathway, and (4) the natural IgM pathway in innate immunity. It is also activated in (1) a classic pathway, i.e., through an antigen-antibody complex, and (2) by injured host cells in acquired immunity. Activation of C3 results in a variety of immunologic reactions such as immune adherence, phagocytosis, antibody response, cytolysis, inflammation, and killing of pathogenic microorganisms. Pathologic pictures of the complement system in various diseases were reviewed. Attention was focused on hypocomplementemia in the malnourished state. In humans and in experimental animals, reduced complement levels, especially of C3, were observed in relation to lowered host defense against infection. Hypocomplementemia improved after nutritional rehabilitation with a concomitant improvement of the clinical picture and recovery of host resistance. Enhancement of C3 levels in malnourished or well-nourished rats resulted in heightened resistance against bacterial infections. On the basis of these experimental and clinical observations, we obtained clues to prevent or treat a compromised host defense system in malnourished states.