Pathogens most commonly enter the body across the epithelial barriers of the mucosa lining the respiratory, digestive, and urogenital tracts, or through damaged skin. Less often, insects, wounds, or hypodermic needles introduce microorganisms directly into the blood. Antibodies protect all the body’s mucosal surfaces, tissues, and blood from such infections; these antibodies serve to neutralize the pathogen or promote its elimination before it can establish a significant infection.
The different classes of antibodies (see Fig. 5.19) are adapted to function in different compartments of the body. Their functional activities and distributions are listed in Fig. 10.27. Because a given V region can become associated with any C region through class switching, the progeny of a single B cell can produce antibodies that share the same specificity yet provide all of the protective functions appropriate for each body compartment. All naive B cells express cell-surface IgM and IgD. IgM is the first antibody secreted by activated B cells but is less than 10% of the immunoglobulin found in plasma. Little IgD antibody is produced at any time, while IgE contributes a small but biologically important part of the immune response. IgG and IgA are the predominant antibody classes. IgE contributes a small but biologically important part of the response. The overall predominance of IgG is also due in part to its longer lifetime in the plasma (see Fig. 5.20).
The major effector functions of each class (+++) are shaded in dark red, whereas lesser functions (++) are shown in dark pink, and very minor functions (+) in pale pink. The distributions are marked similarly, with actual average levels in serum being shown in the bottom row. IgA has two subclasses, IgA1 and IgA2. The IgA column refers to both. *IgG2 can act as an opsonin in the presence of an Fc receptor of the appropriate allotype, found in about 50% of people of Caucasian descent.
IgM antibodies are produced first in a humoral immune response and tend to be of low affinity. However, IgM molecules form pentamers that are stabilized by a single J-chain molecule (see Fig. 5.23) and have 10 antigen-binding sites, conferring higher overall avidity when binding to multivalent antigens such as bacterial capsular polysaccharides. This higher avidity of the pentamer compensates for the low affinity of the individual antigen-binding site within the IgM monomers. Because of the large size of the pentamers, IgM is found mainly in the bloodstream and, to a lesser extent, in the lymph, rather than in intercellular spaces within tissues. The pentameric structure of IgM makes it especially effective in activating the complement system, as we will see in the last part of this chapter. IgM hexamers can also form, and these fix complement much more efficiently than pentamers, possibly because C1q is also a hexamer. However, the in vivo role of IgM hexamers in protecting against infections has not been fully established.
Infection of the bloodstream has serious consequences unless it is controlled quickly, and the rapid production of IgM and its efficient activation of the complement system are important in controlling such infections. Some IgM is produced by conventional B cells that have not undergone class switching, but most is produced by B-1 cells residing in the peritoneal cavity and pleural spaces and by marginal zone B cells of the spleen. These cells secrete antibodies against commonly encountered carbohydrate antigens, including those of bacteria, and do not require T-cell help; they therefore provide a preformed repertoire of IgM antibodies in blood and body cavities that can recognize invading pathogens (see Section 8-9).