Function of Antibodies (Immunoglobulins)

The Antibody’s (Ab)function refers to the biological effect that antibody has on a pathogen or its toxin.

In addition to binding an antigen (Ag), antibodies participate in various biological activities. Though they do not kill or remove pathogens solely by binding with them, they can initiate responses that will result in removal of the antigen or the death of the pathogen. The variables region of the antibody is involved in antigen binding, the heavy chain constant region (CH) is responsible for various collaborative interactions with tissues, cells or proteins that result in the effector function of humoral immunity.

Please remember that ‘not all classes of immunoglobulin (antibody) have the same functions’.

Major functions of the antibodies are:

1. Neutralization of infectivity,
2. Phagocytosis,
3. Antibody-dependent cellular cytotoxicity (ADCC), 
4. Complement-mediated lysis of pathogens or of infected cells:  Antibodies activate the complement system to destroy bacterial cells by lysis
5. Transcytosis, mucosal immunity & neonatal immunity

Another function is unique to Immunoglobulin E (IgE), which is ‘activation of mast cells, eosinophils and basophils’.

Neutralization of Infectivity or Toxins

Antibodies are secreted into the blood and mucosa, where they can block the infectivity of pathogens (bacteria, viruses, parasites and fungi), inactivate or neutralize foreign substances such toxins. Neutralization generally occurs as a result of interfering with an organism’s attachment to host tissues. 

Some antibodies have been shown to inhibit infectivity by binding to organisms and causing them to aggregate. Aggregation or agglutination by IgA may allow more efficient entrapment of bacteria in mucous and subsequent clearance by peristalsis. Although aggregation is more likely to occur with polymeric IgA and IgM, some neutralizing IgG antibodies can aggregate polio virus and reduce the infectivity.  Similarly, Antibodies against HIV-1 gp120 interfere with binding of gp120 to CD4.

Phagocytosis

Antibodies facilitate phagocytosis of foreign substances by a process called opsonization. The internalization and degradation of antibody-coated pathogens by macrophages and neutrophils via FcRs (Fc receptors are protein molecules present on the surfaces of macrophages and neutrophils which can bind the constant region of immunoglobulin molecules) is a critical antibody function for clearance of pathogens in vivo.  

The binding of phagocyte Fc receptors with several antibody molecules complexed with the same target initiates a signal transduction pathway that results in the phagocytosis of the antigen-antibody complex. Inside the phagocyte, the pathogen becomes the target of various destructive processes that include oxidative damage, enzymatic digestion, membrane disrupting effects of antibacterial peptides etc.

Complement-mediated lysis of pathogens or of infected cells

Antibodies (IgM and most IgG subclasses) activate the complement system which can result in the lysis of organisms or of infected cells. An important byproduct of the complement cascade is C3b, which is a protein fragment that can bind nonspecifically to cell and Ag-Ab complexes. Many cell types, for example, red blood cells or macrophages have receptors for C3b and so bind cells or complexes to which C3b has adhered.

Binding of Ag-Ab complexes by the C3b receptors of an RBC allows it to deliver the complexes to liver or spleen where resident macrophages remove them without destroying red blood cell. In addition, organisms or Ag-Ab complexes bound by complement can be internalized by phagocytic cells, with the resultant clearance. Internalization through complement receptors on antigen-presenting cells (APCs) can also result in the processing of antigen for presentation to T lymphocytes.

Antibody-dependent cellular cytotoxicity (ADCC)

Antibodies have shown anti-microbial activity either directly or through interactions with FcRs or complement. ADCC occurs when antibody forms a bridge between an infected target cell (virus infected cells of the host) and an FcR-bearing effector cell, particularly natural killer (NK) cells. The result of this three-way interaction is the death of the target cell, either by lysis or apoptosis.

Tanscytosis, Mucosal Immunity and Neonatal Immunity

Some antibodies can move across epithelial layers (depends on the property of the constant region of that antibody molecule) via a process called transcytosis. IgA is the major immunoglobulin that undergoes transcytosis and is available in secretory form (sIgA) in the mucosal surfaces of respiratory, gastrointestinal and urogenital tracts.

In mammalian species including humans, most subclasses of IgG can cross the placental barrier (since maternal and fetal circulatory system are separate) thus conferring sample of mother’s repertoire of antibody to the developing fetus as protective endowment against pathogens. This passive immunization of developing fetus occurs during the third trimester of gestation.  

Types of Antibodies and their Major Functions  

References and further reading:

• Cellular and Molecular Immunology, 9th Edition
• Kuby Immunology, 8th Edition
• Roitt’s Essential Immunology, 13th Edition