Some insect or animal venoms are so toxic that a single exposure can cause severe tissue damage or death. For these the adaptive immune response is too slow to be protective. Exposure to these venoms is a rare event, and protective vaccines have not been developed for use in humans. Instead, neutralizing antibodies are generated by immunizing other species, such as horses, with insect and snake venoms to produce anti-venom antibodies, or antivenins. The antivenins are injected into exposed individuals to protect them against the toxic effects of the venom. Transfer of antibodies in this way is known as passive immunization (see Appendix I, Section A-30).
Animal viruses infect cells by binding to a particular cell-surface receptor. These are often cell-type-specific proteins that determine which cells a virus can infect, or its tropism. Many antibodies that neutralize viruses do so by directly blocking the binding of virus to surface receptors (Fig. 10.33). The hemagglutinin of influenza virus, for example, binds to terminal sialic acid residues on the carbohydrates of glycoproteins present on epithelial cells of the respiratory tract. It is known as hemagglutinin because it recognizes and binds to similar sialic acid residues on chicken red blood cells and agglutinates these red blood cells. Antibodies against the hemagglutinin can prevent infection by the influenza virus. Such antibodies are called virus-neutralizing antibodies, and, as with the neutralization of toxins, high-affinity IgA and IgG antibodies are particularly important. However, antibodies can also neutralize viruses by interfering with the fusion mechanisms used to enter the cell’s cytoplasm after binding to surface receptors.
Many bacteria have cell-surface molecules called adhesins that enable them to bind to the surface of host cells. This adherence is crucial to the ability of these bacteria to cause disease, whether they subsequently enter the cell, as do Salmonella species, or remain attached to the cell surface as extracellular pathogens (Fig. 10.34). Neisseria gonorrhoeae, the causative agent of the sexually transmitted disease gonorrhea, has a cell-surface protein known as pilin that enables the bacterium to adhere to the epithelial cells of the urinary and reproductive tracts and is essential to its infectivity. Antibodies against pilin can inhibit this adhesive reaction and prevent infection.
IgA antibodies secreted onto the mucosal surfaces of the intestinal, respiratory, and reproductive tracts are particularly important in inhibiting the colonization of these surfaces by pathogens and in preventing infection of the epithelial cells. Adhesion of bacteria to cells within tissues can also contribute to pathogenesis, and IgG antibodies against adhesins protect tissues from damage in much the same way as IgA antibodies protect mucosal surfaces.
Fig. 10.33 Viral infection of cells can be blocked by neutralizing antibodies. For a virus to multiply within a cell, it must introduce its genes into the cell. The first step in entry is usually the binding of the virus to a receptor on the cell surface. For enveloped viruses, as shown in the figure, entry into the cytoplasm requires fusion of the viral envelope and the cell membrane. For some viruses this fusion event takes place on the cell surface (not shown); for others it can occur only within the more acidic environment of endosomes, as shown here. Non-enveloped viruses must also bind to receptors on cell surfaces, but they enter the cytoplasm by disrupting endosomes. Antibodies bound to viral surface proteins neutralize the virus, inhibiting either its initial binding to the cell or its subsequent entry.
10-19 Antibody:antigen complexes activate the classical pathway of complement by binding to C1q.