The COVID-19 Textbook
Fc α R
IgA
Fc γ RIIA
Fc γ R
IgG
NK cell
Neutrophil
• Fc γ Rs on innate effector cells are engaged by the Fc domain of antibodies that are bound to viral proteins on the surface of virus-infected cells
• IgG or IgA mediated neutrophil activation opsonophagocytosis and stimulation of NETogis • Infected cells cleared by ADCP and ADCC
• Viral particles are trapped and inactivated in NETS resulting in release of proteases, antimicrobial peptides and ROS that can result in aberrant inflammation
ADCC
• Release of cytotoxic granules contributes to pathology
Perforins
& granzymes
B cell
Infected cell
• Crosslinking of BCR activates B cells • Uptake of immune complexes by DCs and antigen presentation to T cells SARS-CoV-2 spike protein
IgG BCR TCR
Membrane attack complex (MAC)
• IgG or light binds to viral antigen on the surface of infected cell • Clq binds to these antibodies resulting in formation of MAC and lysis of target cell
T cell DC
CDC
Complement
SARS-CoV-2
MHC
FIGURE 8.2 Antibody effector functions . ADCC, antibody-dependent cellular cytotoxicity; ADCP, antibody-dependent cellular phagocytosis; BCR, B-cell receptor; CDC, complement-dependent cytotoxicity; DC, dendritic cell; Ig, immunoglobulin; MHC, major histocompatibility complex; SARS-CoV, severe acute respiratory syndrome coronavirus; TCR, T-cell receptor. (Adapted from Zhang A, Stacey HD, D’Agostino MR, Tugg Y, Marzok A, Miller MS. Beyond neutralization: Fc-dependent antibody effec tor functions in SARS-CoV-2 infection. Nat Rev Immunol . 2022. doi:10.1038/s41577-022-00813-1) 253
Costimulatory signals
• Antibody-opsonized target cells activate the Fc γ Rs on the surface of effector cells to induce phagocytosis • This results in internalization and degradation of the target cell through phagosome acidification
Immunomodulation
Fc γ R
Phagocytic cell
Fc γ RIIA
• Viral degradation results in enhanced MHCI and MHCII antigen presentation
Copyright © 2023 Wolters Kluwer, Inc. Unauthorized reproduction of the content is prohibited. ADCP
lysed target cell
Cytokines
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