Antibodies produced in response to a foreign antigen are characterized by polyclonality, not only in the diverse epitopes to which their variable domains bind but also in the various effector molecules to which their constant regions (Fc domains) engage. Thus, while Fab-antigen interactions are crucial to the specificity of the antibody response, there is a crucial role for the Fc domain in mediating the diverse effector properties triggered by antigen recognition, even for processes traditionally attributed solely to recognition by the Fab, such as neutralization of toxins and viruses. Specific interactions of the IgG Fc domain with distinct receptors expressed by diverse immune cell types result in the pleiotropic effector functions for IgG, including the clearance of pathogens and toxins, lysis and removal of infected or malignant cells, modulation of the innate and adaptive branches of immunity to shape an immune response, and initiation of anti-inflammatory pathways that actively suppress immunity. The Fc domain mediates these diverse effector activities by engaging[LINE SEPARATOR]two distinct classes of Fc receptors (type I and type II) on the basis of[LINE SEPARATOR]the distinct conformational states that the Fc domain may adopt. These conformational states are regulated by the differences among antibody subclasses in their amino acid sequence and by the complex, biantennary Fc-associated N-linked glycan. I will discuss the diverse downstream proinflammatory, anti-inflammatory and immunomodulatory consequences of the engagement of type I and type II Fc receptors in the context of infectious diseases.
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