IgG-mediated immune effector pathways

IgG-mediated immune effector pathways represent the critical link between the adaptive immune system's specificity and the innate immune system's destructive capabilities (Nimmerjahn & Ravetch, 2008). These pathways are activated when IgG antibodies bind to their cognate antigens, forming immune complexes that subsequently engage Fcγ receptors (FcγRs) on effector cells like natural killer cells and macrophages, or activate the classical complement cascade via C1q binding (Ricklin et al., 2010). Engagement of FcγRs triggers mechanisms such as antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), while complement activation leads to complement-dependent cytotoxicity (CDC) and opsonization (Wang et al., 2018). These processes are fundamental to the efficacy of many therapeutic monoclonal antibodies used in oncology and infectious diseases, but their dysregulation is also central to the pathogenesis of autoimmune and inflammatory disorders (Nimmerjahn & Ravetch, 2008). Therapeutic strategies often involve enhancing these pathways to eliminate tumor cells or inhibiting them to treat antibody-mediated autoimmune conditions (Wang et al., 2018).

Other names

Antibody-dependent cellular cytotoxicity (ADCC)Antibody-dependent cellular phagocytosis (ADCP)Complement-dependent cytotoxicity (CDC)IgG-FcγR-Complement axisType II hypersensitivity mechanismsAntibody-mediated effector functions

IgG antibodies bind to specific antigens on target cells; the Fc portion of the IgG then interacts with Fcγ receptors on innate immune cells to trigger ADCC/ADCP or binds C1q to initiate the classical complement pathway leading to CDC (Nimmerjahn & Ravetch, 2008; Ricklin et al., 2010).