Pathogenic Exploitation of Fc Activity

While the benefits of antibody responses are widely known, pathogens are also able to exploit antibodies to facilitate cell entry and potentially alter the cellular response via interactions with Fc receptors. This phenomenon, known as antibody-dependent enhancement (ADE) of disease, is a factor in numerous human and veterinary diseases. It is thought to result from innate cellular responses to Fcγ receptor-facilitated entry of infectious microbial immune complexes, and paradoxically results in increased production of pathogenic organisms. ADE has been described in vitro in numerous settings, but the strongest data regarding the in vivo impact of this mechanism on human disease come from human disease and animal models of dengue and leishmanial infections. This chapter reviews the literature of ADE in relation to the innate immune responses to Fcγ receptor ligation by infectious IgG immune complexes and discusses the research frontiers regarding this harmful antibody activity.