The major antibody class in the blood is IgG. These antibodies are four-chain monomers (see Figure 24–23), and they are produced in especially large quantities during secondary antibody responses. The tail region of some subclasses of IgG antibodies that are bound to antigen can activate complement and also bind to specific receptors on macrophages and neutrophils. Largely by means of such Fc receptors (so-named because antibody tails are called Fc regions), these phagocytic cells bind, ingest, and destroy infecting microorganisms that have become coated with the IgG antibodies produced in response to the infection; the activated Fc receptors also signal the phagocyte to secrete pro-inflammatory cytokines (Movie 24.4).
The tail region of IgE antibodies binds to another class of Fc receptors on the surface of mast cells in tissues and of basophils in the blood. Because antigen-free IgE antibodies bind with high affinity to such Fc receptors, the antibodies act as antigen receptors on these cells. Antigen binding to the bound antibodies activates the Fc receptors and stimulates the cells to secrete a variety of cytokines and biologically active amines, especially histamine, which causes blood vessels to dilate and become leaky; this helps leukocytes, antibodies, and complement components to enter sites where mast cells have been activated. The release of amines from mast cells and basophils is largely responsible for the symptoms of such allergic reactions as hay fever, asthma, and hives. In addition, mast cells secrete factors that attract and activate leukocytes called eosinophils, which also have Fc receptors that bind IgE molecules and can kill extracellular parasitic worms, especially if the worms are coated with IgE antibodies (see Figure 24–6).
IgA is the principal antibody class in secretions, including saliva, tears, milk, and respiratory and intestinal secretions. Yet another class of Fc receptors, located on the relevant epithelial cells, guides the secretion by binding antigen-free IgA dimers and transporting them across the epithelium. The properties of the various classes of antibodies in humans are summarized in Table 24–2.
All classes of Ig can be made in a membrane-bound form, as well as in a soluble, secreted form. The two forms differ only in the C-terminus of their heavy chain. The heavy chains of membrane-bound Ig molecules (BCRs) have a trans-membrane hydrophobic C-terminus, which anchors them in the lipid bilayer of the B cell’s plasma membrane. The heavy chains of secreted antibody molecules, by contrast, have instead a hydrophilic C-terminus, which allows them to escape from the cell. The switch in the character of the Ig molecules made occurs because the activation of B cells by antigen and helper T cells induces a change in the way in which the heavy-chain RNA transcripts are made and processed in the nucleus (see Figure 7–59).