Many pathogens multiply in the body’s extracellular spaces, and even intracellular pathogens can spread by moving through the extracellular fluids. The extracellular spaces are protected by the humoral immune response, in which antibodies produced by B cells act to destroy extracellular microorganisms and their products, and prevent the spread of intracellular infections. As we introduced in Section 1-20, antibodies contribute to immunity in three main ways: neutralization, opsonization, and complement activation (Fig. 10.1). Antibodies can bind to pathogens and prevent their ability to enter and infect cells, and therefore are thus said to neutralize the pathogen; antibodies may also bind bacterial toxins, preventing their action or ability to enter cells. Antibodies also facilitate opsonization, the uptake of the pathogens by phagocytes, by binding to Fc receptors through their constant regions (C regions). Finally, antibodies bound to pathogens can activate proteins of the classical pathway of the complement system, as we described in Chapter 2. This can increase opsonization by placing other complement proteins onto the pathogen’s surface, help recruit phagocytic cells to the site of infection, and activate the membrane-attack complex, which can directly lyse certain microorganisms by forming pores in their membranes. The choice of which effector mechanisms are used is influenced by the heavy-chain isotype of the antibodies produced, which determines their class (see Section 5-12).
In the first part of this chapter, we describe the interactions of naive B cells with antigen and with helper T cells that lead to the activation of B cells and antibody production. Some microbial antigens can provoke antibody production without T-cell help, but activation of naive B cells by antigens usually involves help from T follicular helper (TFH) cells (see Section 9-20). Activated B cells then differentiate into antibody-secreting plasma cells and memory B cells. Most antibody responses undergo a process called affinity maturation, in which antibodies of greater affinity for their target antigen are produced by the somatic hypermutation of antibody variable-region (V-region) genes. We examine the molecular mechanism of somatic hypermutation and its immunological consequences, as well as class switching—a process that generates the different classes of antibodies that confer functional diversity on the antibody response. Both affinity maturation and class switching occur only in B cells and require T-cell help. In the second part of the chapter, we introduce the distributions and functions of various classes of antibody, in particular those secreted into mucosal sites. In the third part of the chapter, we discuss in detail how the Fc region of the antibody engages various effector mechanisms to contain and eliminate infections. Like the T-cell response, the humoral immune response produces immunological memory, and this is discussed in Chapter 11.
Fig. 10.1 Antibodies mediate the humoral immune response through neutralization, opsonization, and complement activation. After being secreted by plasma cells, antibodies protect the host from infection in three main ways. They can inhibit the toxic effects or infectivity of pathogens or their products by binding to them, a process called neutralization (top panel). When bound to pathogens, the antibody’s Fc region can bind to Fc receptors on accessory cells, such as macrophages and neutrophils, helping these cells to ingest and kill the pathogen. This process is called opsonization (middle panel). Antibodies can trigger complement by activating C1, the first step in the classical complement pathway. Deposition of complement proteins enhances opsonization and can also directly kill certain bacterial cells by activating the membrane-attack complex (bottom panel).
B-cell activation by antigen and helper T cells.
The distributions and functions of immunoglobulin classes.
The destruction of antibody-coated pathogens via Fc receptors.