Antigen:antibody complexes can also be a cause of pathology in patients with deficiencies in the early components of complement (C1, C2, and C4). These deficiencies result in the classical complement pathway not being activated properly, and immune complexes not being cleared effectively because they do not become tagged with complement. These patients also suffer tissue damage as a result of immune-complex deposition, especially in the kidneys.
Summary.
The T-cell-dependent antibody response begins with IgM secretion but quickly progresses to the production of additional antibody classes. Each class is specialized both in its localization in the body and in the functions it can perform. IgM antibodies are found mainly in blood; they are pentameric in structure. IgM is specialized to activate complement efficiently upon binding antigen and to compensate for the low affinity of a typical IgM antigen-binding site. IgG antibodies are usually of higher affinity and are found in blood and in extracellular fluid, where they can neutralize toxins, viruses, and bacteria, opsonize them for phagocytosis, and activate the complement system. IgA antibodies are synthesized as monomers, which enter blood and extracellular fluids, or they are secreted as dimeric molecules by plasma cells in the lamina propria of various mucosal tissues. IgA dimers are selectively transported across the epithelial layer into sites such as the lumen of the gut, where they neutralize toxins and viruses and block the entry of bacteria across the intestinal epithelium. Most IgE antibody is bound to the surface of mast cells that reside mainly just below the body surface; antigen binding to this IgE triggers local defense reactions. Antibodies can defend the body against extracellular pathogens and their toxic products in several ways. The simplest is by direct interactions with pathogens or their products, for example, by binding to the active sites of toxins and neutralizing them or by blocking their ability to bind to host cells through specific receptors. When antibodies of the appropriate isotype bind to antigens, they can activate the classical pathway of complement, which leads
Fig. 10.37 Erythrocyte CR1 helps to clear immune complexes from the circulation.
Small antigen:antibody complexes form in the circulation
FcRIn the spleen and liver, phagocytic cells remove the immune complexes from the erythrocyte surface Complement receptor CR1 on erythrocytes binds the immune complexes via bound C3b CR1 to the elimination of the pathogen by the various mechanisms described in Chapter 2. Soluble immune complexes of antigen and antibody also fix complement and are cleared from the circulation via complement receptors on red blood cells.
The destruction of antibody-coated pathogens via Fc receptors.
The neutralization of toxins, viruses, or bacteria by high-affinity antibodies can protect against infection but does not, on its own, solve the problem of how to remove the pathogens and their products from the body. Moreover, many pathogens cannot be neutralized by antibody and must be destroyed by other means. Many pathogen-specific antibodies do not bind to neutralizing targets on pathogen surfaces and thus need to be linked to other effector mechanisms to play their part in host defense. We have already seen how the binding of antibody to antigen can activate complement. Another important defense mechanism is the activation of a variety of accessory effector cells bearing receptors called Fc receptors because they are specific for the Fc portion of antibodies. These receptors facilitate the phagocytosis of antibody-bound extracellular pathogens by macrophages, dendritic cells, and neutrophils. Other, nonphagocytic cells of the immune system—NK cells, eosinophils, basophils, and mast cells (see Fig. 1.8)—are triggered to secrete stored mediators when their Fc receptors are engaged by antibody-coated pathogens. These mechanisms maximize the effectiveness of all antibodies regardless of where they bind.