Some of the progeny of the expanded B-cell clones differentiate into antibody-secreting plasma cells. Each plasma cell secretes antibodies with the same specificity as the cell surface antibodies (B-cell antigen receptors) that first recognized the antigen. Polysaccharides and lipids stimulate secretion mainly of IgM antibody. Protein antigens, by virtue of CD40L-and cytokine-mediated helper T-cell actions, induce the production of antibodies of different classes (IgG, IgA, IgE).  Production of functionally different antibodies, all with the same specificity, relies on heavy-chain class (isotype) switching, which increases the range of functions that antibodies serve. Some of the isotype-specific functions of antibodies include opsonization and transplacental transfer of IgG, IgA secretion into mucosal lumens, and binding of IgE to mast cells. Helper T cells also stimulate the production of antibodies with higher affinity for the antigen. This process, called affinity maturation, improves the quality of the humoral immune response. Some activated B cells migrate into follicles and form germinal centers, which are the major sites of isotype switching and affinity maturation. The helper T cells that stimulate these processes in B lymphocytes also migrate to and reside in the germinal centers and are called follicular helper T (Tfh) cells.
The humoral immune response combats microbes in numerous ways (see
Fig. 5.11
Antibodies bind to microbes and prevent them from infecting cells, thereby neutralizing the microbes.
IgG antibodies coat (opsonize) microbes and target them for phagocytosis, since phagocytes (neutrophils and macrophages) express receptors for the Fc tails of IgG molecules.
IgG and IgM activate the complement system by the classical pathway, and complement products promote phagocytosis and destruction of microbes.
IgA is secreted in mucosal tissues and neutralizes microbes in the lumens of the respiratory and gastrointestinal tracts (and other mucosal tissues).
IgG is actively transported across the placenta and protects the newborn until the immune system becomes mature. This is a form of passive immunity.
IgE coats helminthic parasites and functions with mast cells and eosinophils to kill them.
Circulating IgG antibodies have half-lives of about 3 weeks, which is much longer than the half-lives of most blood proteins, as a consequence of special mechanisms for recycling IgG and reducing its catabolism. Some antibody-secreting plasma cells migrate to the bone marrow and live for years, continuing to produce low levels of antibodies.
The majority of effector lymphocytes induced by an infectious pathogen die by apoptosis after the pathogen is eliminated, thus returning the immune system to its basal resting state. The initial activation of lymphocytes generates long-lived memory cells, which may survive for years after the infection. Memory cells are an expanded pool of antigen-specific lymphocytes (more numerous than the naïve cells specific for any antigen that are present before encounter with that antigen), and they respond faster and more effectively when reexposed to the antigen than do naïve cells. This is why the generation of memory cells is an important goal of vaccination.
THENORMALIMMUNERESPONSE:OVERVIEWOFCELLS,TISSUES,RECEPTORS,ANDMEDIATORS
Theinnateimmunesystemusesseveralfamiliesofreceptors,suchastheToll-likereceptors,torecognizemoleculespresentinvarioustypesofmicrobesandproducedbydamagedcells.
Lymphocytesarethemediatorsofadaptiveimmunityandtheonlycellsthatproducespecificanddiversereceptorsforantigens.