Antibody Functions

Antibodies protect against extracellular pathogens and their toxic products. The biological functions of antibodies can be attributed to particular classes of the heavy chain. The antibody exhibits characteristic functions upon pathogen recognition and FcγR engagement including neutralization of infectivity, antibody-dependent cellular cytotoxicity (ADCC), phagocytosis, and complement-mediated lysis of pathogens or infected cells.

Fig.1 Antibodies can participate in host defense in three main ways. (Spasevska, 2015)

Neutralization of Infectivity

Fig.2 Proposed viral neutralization mechanism of 8C11-mediated physical collision. (Zheng, 2019)

For the most part, antibodies by themselves can neutralize organism infectivity to reduce the number of encounters between pathogens and host cells. Neutralization generally occurs as a result of interfering with an organism’s attachment to host tissues. Antibodies can prevent pathogens or their products is by binding to them and thereby blocking their access to host cells. The toxin: antibody complex cannot react with receptors on the host cell, whereas unbound toxin can react. Antibodies also neutralize complete virus particles and bacterial cells. The antigen: antibody complex is finally scavenged and degraded by phagocytes. Some antibodies have been shown to prevent infectivity by binding to organisms and causing them to aggregate. For example, aggregation or agglutination by immunoglobulin A (IgA) may allow more efficient entrapment of bacteria in mucus. Some neutralizing IgG antibodies can aggregate poliovirus.

Opsonization and Phagocytosis

Antibodies coating an antigen render it recognizable as foreign by phagocytes (macrophages and neutrophils), which then ingest and destroy it, that is called opsonization. Much of the biological activity of antibodies is mediated through interactions between Fc and Fc receptors found on many cells important for host defense. Interactions between Fc and FcRs can result in the death of pathogens or cells infected with pathogens by a process known as ADCC. ADCC occurs when an antibody forms a bridge between an infected target cell (or directly with some pathogens) and an FcR-bearing effector cell. The bridge makes effector cells close to pathogens and actives phagocytes. This interaction eventually results in the death of the target cell, either by lysis or apoptosis. Fc-FcR interactions are also necessary for the phagocytosis of pathogens or of infected cells. Engagement of FcRs can also inhibit intracellular pathogens without apparently killing the host cell.

Activation of the Complement System

A unique function of antibodies is to initiate the clearance of pathogens via complement system activation. The complement system is activated by the microbial surface or with antibodies bound to surface, leading to a certain complement component bound onto the microbial surface. Most phagocytes express the complement receptor (CR). The CR on the phagocytes can recognize the complement to stimulate the phagocytes to ingest and destroy the pathogens. Completion of the complement cascade causes the formation of a membrane-attack complex, that disrupts the cell membrane and causes cell lysis. The result is that all pathogens and free molecules bound by antibodies are eventually delivered to phagocytes for ingestion, degradation, and removal from the body. The complement system and the phagocytes that antibodies recruit are not themselves antigen-specific, and they depend upon antibody molecules to mark the particles as foreign.

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References

1. Spasevska, I.; et al. Advances in bispecific antibodies engineering: Novel concepts for immunotherapies. J Blood Disord Transfus. 2015, 6: 243.
2. Zheng, Q.; et al. Viral neutralization by antibody-imposed physical disruption. Proc Natl Acad Sci U S A. 2019, 116(52): 26933-26940.

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