The role of antibody and complement in the control of viral infections.

Host defense against viral infection is extremely complex and includes both humoral and cellular immune mechanisms. This contribution examines the mechanisms by which antibody (Ab) and the complement (C) system, major constituents of the humoral immune system, inactivate viruses and block viral maturation in virus-infected cells in vitro. Ab and C may neutralize viruses by envelopment in a coating of protein, by aggregation by lysis, or by facilitating interactions with various effector cells. Ab and C molecules deposited on the surfaces of viruses may physically interfere with the ability of the virus to infect a potentially susceptible cell. This appears to be the most common mechanism by which Ab and C neutralize viruses. In rare instances, Ab and/or C may aggregate viruses; aggregation reduces the net number of infectious particles and thus is manifest as neutralization. C may lyse enveloped viruses, resulting in irreversible viral inactivation. However, this does not appear to be a major mechanism of viral neutralization. Finally, the Fc portions of bound Ab molecules as well as bound C molecules may interact with effector cells with specific receptors for these factors and thereby facilitate viral destruction. In regard to virus-infected cells, the deposition of Ab or C on the cell surface may prevent the maturation or release of viral particles and alter normal cellular functions. Ab and C may also lyse virus-infected cells, abruptly stopping further viral maturation. Such lytic events require only the F(ab')2 portion of the Ab molecule and proceed via activation of the alternative C pathway. Effector cells may also interact with Ab and/or C molecules deposited on virus-infected cells, leading to cytotoxic reactions and/or ingestion depending on the type of effector cell involved. The activated C system has the ability to produce an acute inflammatory response leading to alterations in vessel permeability, edema, changes in smooth-muscle contractility, and the influx of leukocytes. Such inflammatory responses occurring in tissues, including the skin, as a result of C activation not only retard the spread of the infection and facilitate the destruction of the infectious agent, but also in all likelihood damage normal tissues in the vicinity. In addition, C activation in tissues also has the ability to stimulate arachidonic acid metabolism and induce the release of histamine and other mediators as well as pyrogens from appropriate cell types. A number of the systemic symptoms characteristic of viral infections, such as headaches, myalgias, and fever, likely result from such processes.