Complement Effector Mechanisms in Health and Disease

Complement is an effector system able to mediate a number of biological activities in vitro and in vivo. Most familiar is the ability of the system to mediate the lytic destruction of numerous kinds of cells and pathogenic organisms including bacteria, viruses, and virus-infected cells. In addition, the complement system also activates neutrophils, monocytes, basophils, mast cells, and lymphocytes to perform specialized functions. While generally considered to be confined to the effector side of immune reactions, recent evidence indicates that the complement system also directly recognizes and is triggered by a number of bacteria and viruses as well as virus-infected cells in the absence of antibody. In such reactions, complement fulfills the recognition role normally associated with the antibody molecule or immune lymphocyte. The complement system may thus also function as a natural surveillance system operative prior to the induction of specific immunity. Involvement of the complement system in biological reactions has been ascertained by several techniques over the years. These include quantitation of individual complement components in human sera and demonstration of complement deposition in diseased tissues in human diseases and in experimental diseases in animals. Such techniques, however, have limitations in specificity and sensitivity. Assays which detect specific features of the complement activation process have become available in recent years. These tests detect the physical, chemical, or antigenic changes characteristic of the complement activation process. These assays are extremely specific and quantitative; furthermore, most are usable with samples from patients. Three general approaches have been utilized to develop such specific quantitative assays for complement activation. The first includes assays which quantitate activation-specific limited proteolysis of the complement components. The second type of assay includes tests which detect and quantitate new antigens or other activation-specific antigenic changes. The third category is represented by assays which detect and quantitate the protein-protein complexes characteristic of the activation process. Examples of tests presenting each of these approaches are given. Data from the above approaches together with studies of in vitro participation and functions of complement molecules in selected reactions such as opsonization, phagocytosis, chemotaxis, smooth muscle contraction, mediator release, etc., indicate that the two most important biological functions of complement are first, the production of an acute inflammatory response and second, the destruction of infectious agents. Acute inflammatory responses serve to confine infective processes and thus dissemination. The second major in vivo function pertains to the role of the complement system in the control infection. The complement system directly aids in the destruction of bacteria, viruses, and virus-infectec cells by several mechanisms, and facilitates interactions with effector cells leading to either phagocytosis or extracellular destruction of pathogens. These processes and their interrelationships are described.