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

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lysed target cell

Cytokines