Pathogens can cause damage to a host by producing toxins or by infecting cells directly, and antibodies can protect by blocking both of these actions. Many bacteria cause disease by secreting toxins that damage or disrupt the function of the host’s cells (Fig. 10.31). To affect cells, many toxins consist of separate domains for exerting toxicity and for binding to specific cell-surface receptors by which they enter cells. Antibodies that bind a toxin’s receptor-binding site can prevent cell entry and protect cells from attack (Fig. 10.32). Antibodies that act in this way to neutralize toxins are referred to as neutralizing antibodies. Most toxins are active at nanomolar concentrations: a single molecule of diphtheria toxin can kill a cell. To neutralize toxins, therefore, antibodies must be able to diffuse into the tissues and bind the toxin rapidly and with high affinity. The ability of IgG antibodies to diffuse easily throughout the
Fig. 10.30 Immunoglobulin classes are selectively distributed in the body. IgG and IgM predominate in blood (shown here for simplicity by IgM and IgG in the heart), whereas IgG and monomeric IgA are the major antibodies in extracellular fluid within the body. Dimeric IgA predominates in secretions across epithelia, including breast milk. The fetus receives IgG from the mother by transplacental transport. IgE is found mainly associated with mast cells just beneath epithelial surfaces (especially of the respiratory tract, gastrointestinal tract, and skin). The brain is normally devoid of immunoglobulin.
Fig. 10.31 Many common diseases are caused by bacterial toxins. The toxins shown here are all exotoxins—proteins secreted by the bacteria. High-affinity IgG and IgA antibodies protect against these toxins. Bacteria also have nonsecreted endotoxins, such as lipopolysaccharide, which are released when the bacterium dies and may also mediate pathogenesis of disease. Host responses to exotoxins are more complex because the innate immune system has receptors for some endotoxins, such as TLR-4 (see Chapter 3).
extracellular fluid, and their high affinity for antigen once affinity maturation has taken place, make them the principal antibodies that neutralize toxins in tissues. High-affinity IgA antibodies similarly neutralize toxins at the mucosal surfaces of the body.
Dissociation of toxin releases its active chain, which poisons cell Antibody protects cell by blocking binding of toxin Toxin binds to cellular receptors Endocytosis of toxin:receptor complexes
Fig. 10.32 Neutralization of toxins by IgG antibodies protects molecule binds a cell-surface receptor, which enables the molecule cells from damage. The damaging effects of many bacteria are to be internalized. Another part of the toxin molecule then enters the due to the toxins they produce (see Fig. 10.31). These toxins are cytoplasm and poisons the cell. Antibodies that inhibit toxin binding usually composed of several distinct moieties. One part of the toxin can prevent, or neutralize, these effects.
Diphtheria and tetanus toxins are two bacterial toxins in which the toxic and receptor-binding functions are on separate protein chains. It is therefore possible to immunize individuals, usually as infants, with modified toxin molecules in which the toxic chain has been denatured. These modified toxins, called toxoids, lack toxic activity but retain the receptor-binding site. Thus, immunization with the toxoid induces neutralizing antibodies that protect against the native toxin.