Effector Functions of Antibodies

A – Functions Mediated by the Fab Fragment

A- 1 Neutralization of Bacterial Toxins

Many bacteria exert pathogenicity by secreting proteins called toxins, which can damage or destroy host cells. To act, toxins must bind specific receptors on target cells. Most toxins consist of two subunits: one mediates receptor binding and internalization, while the other is responsible for toxicity.

Neutralizing antibodies bind the toxin via their Fab fragment, blocking receptor interaction and preventing intracellular entry. Effective neutralization requires antibodies to diffuse rapidly into tissues and bind toxins with high affinity.

  • IgG: primary defense against toxins in the extracellular compartment due to high diffusion and affinity.

  • IgA: efficiently neutralizes toxins at mucosal surfaces.

Vaccines often use toxoid molecules (toxins rendered non-toxic but retaining antigenicity) to induce neutralizing antibodies. Rarely, exposure to highly toxic venoms may require passive immunization via antivenom therapy using antibodies produced in animals.

A-2 Blocking Viral Infectivity

Viruses must bind specific cell surface receptors to infect cells, determining viral tropism. Example: influenza virus uses hemagglutinin to bind sialic acid residues on respiratory epithelial cells.

  • High-affinity IgG and IgA antibodies block viral binding and can disrupt viral particle structure, preventing membrane fusion and infection.

A-3 Inhibition of Bacterial Adhesion

Many bacteria express adhesins enabling attachment to host cells. Antibodies targeting these adhesins prevent adhesion and infection.

  • Example: Neisseria gonorrhoeae pilin binds urinary and genital epithelium; antibodies against pilin block adherence and virulence.

B- Functions Mediated by the Fc Fragment

B-1 Introduction and Antibody Transport

Extracellular pathogens require antibodies to diffuse effectively for neutralization. Antibody localization depends on isotype, which can restrict or facilitate transport to specific tissues.

  • IgM: pentameric, low-affinity antibodies produced early in humoral responses. Ten antigen-binding sites increase avidity, compensating for low affinity. Primarily intravascular, highly efficient at complement activation.

  • IgG: monomeric, small, high-affinity antibodies; diffuse easily into tissues. Efficient at opsonization and complement activation.

  • IgA: present in serum and mucosal surfaces; does not activate complement; acts mainly as a neutralizing antibody at epithelial barriers.

  • IgE: very low serum concentration; binds mast cells and basophils; mediates rapid defense and allergic responses.

B-1-1 IgA Transport via Transcytosis

  • Produced by plasmocytes in lamina propria, IgA is secreted as dimers linked by J-chain.

  • Binds the poly-Ig receptor on the basolateral surface of epithelial cells, internalized, and transported to the apical surface (transcytosis).

  • Proteolytic cleavage releases IgA with secretory component, protecting it from enzymatic degradation.

  • Main sites: intestine, lung, maternal milk, tears, saliva.

  • Function: protect epithelial surfaces against infection; block bacterial adhesion and toxins.

B-1-2 Maternal IgG Transfer

  • IgG crosses the placenta via Fc receptors; newborns acquire maternal IgG, providing immediate passive immunity.

  • IgA in maternal milk protects the neonatal gut until endogenous IgA is produced.

B-2 Interactions Between Antibodies and Effector Cells

High-affinity antibodies neutralize pathogens but cannot eliminate them alone. Clearance often requires:

  • Complement activation → opsonization and enhanced phagocytosis.

  • Fc receptor (FcR) engagement on effector cells: phagocytes, eosinophils, NK cells, mast cells.

B-2-1 FcR Specificity and Isotype Matching

  • Fc receptors are a multimolecular family that recognize specific antibody classes.

  • The antibody isotype determines which effector cell is recruited.

  • FcRs contain ITAM motifs for signal transduction; some receptors, like FcγRIIB, are inhibitory (ITIM-mediated).

  • Langerhans cells and follicular dendritic cells use FcRs to capture immune complexes and present antigens, promoting humoral responses.

B-2-2 Activation of FcR by Immune Complexes

  • Phagocytes are activated by IgG1 and IgG3 antibodies bound to pathogens.

  • FcR aggregation upon binding multimeric immune complexes increases phagocytic efficiency.

  • Free antibodies with low-affinity binding do not trigger phagocyte activation, preventing unnecessary inflammation.

B-2-3 Opsonization and Phagocytosis

  • Macrophages and neutrophils recognize pathogens coated with antibodies (opsonization).

  • Pathogens are internalized into phagosomes, fused with lysosomes to form phagolysosomes, and destroyed by proteolytic enzymes and reactive oxygen/nitrogen species.

  • FcR aggregation enhances the production of radicals and phagocytic activity.

B-2-4 NK Cell-Mediated Cytotoxicity (ADCC)

  • Virus-infected cells expressing surface antigens can be killed by NK cells.

  • IgG-coated targets engage FcγRIII (CD16) on NK cells, triggering Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC).

  • Mechanism involves perforin-granzyme system, similar to CD8+ T cell cytotoxicity.

B-2-5 High-Affinity Fcε Function

  • Mast cells reside under mucosal surfaces; granules contain histamine and mediators.

  • Activated by IgE binding to FcεRI or IgG to FcγRIII when antigens crosslink antibodies.

  • Degranulation releases mediators causing vasodilation, vascular permeability, and immune cell recruitment.

B-2-6 Role of IgE in Anti-Parasitic Immunity

  • IgE: mediated mast cell activation recruits eosinophils and basophils to infection sites.

  • IgE, eosinophils and mast cells contribute to defense against helminthic infections.

  • Evidence: mastocytosis during intestinal helminth infection; mast-cell-deficient mice show higher susceptibility; eosinophils kill parasites in the presence of specific IgE.