The humoral immune response to infection involves the production of antibody by plasma cells derived from B lymphocytes, the binding of this antibody to the pathogen, and the elimination of the pathogen by phagocytic cells and molecules of the humoral immune system. The production of antibody usually requires the action of helper T cells specific for a peptide fragment of the antigen recognized by the B cell, a phenomenon called linked recognition. An activated B cell first moves to the T-zone–B-zone boundary in secondary lymphoid tissues, where it may encounter its cognate T cell and begin to proliferate. Some B cells become plasmablasts, while others move to the germinal center, where somatic hypermutation and class switch recombination take place. B cells that bind antigen with the highest affinity are selected for survival and further differentiation, leading to affinity maturation of the antibody response. Cytokines made by helper T cells direct class switching, leading to the production of antibody of various classes that can be distributed to various body compartments.
IgM antibodies are produced early in an infection by conventional B cells and are also made in the absence of infection by subsets of nonconventional B cells in particular locations (as natural antibodies). IgM has a major role in protecting against infection in the bloodstream, whereas isotypes secreted later in an adaptive immune response, such as IgG, diffuse into the tissues. Antigens that have highly repeating antigenic determinants and that contain mitogens— called TI antigens—can elicit IgM and some IgG independently of T-cell help, and this provides an early protective immune response. Multimeric IgA is produced in the lamina propria and is transported across epithelial surfaces, whereas IgE is made in small amounts and binds avidly to receptors on the surface of basophils and mast cells.
Antibodies that bind with high affinity to critical sites on toxins, viruses, and bacteria can neutralize them. However, pathogens and their products are destroyed and removed from the body largely through uptake into phagocytes and degradation inside these cells. Antibodies that coat pathogens bind to Fc receptors on phagocytes, which are thereby triggered to engulf and destroy the pathogen. Binding of antibody C regions to Fc receptors on other cells leads to the exocytosis of stored mediators; this is particularly important in parasite infections, in which Fcε-expressing mast cells are triggered by the binding of antigen to IgE antibody to release inflammatory mediators directly onto parasite surfaces. Antibodies can also initiate the destruction of pathogens by activating the complement system. Complement components can opsonize pathogens for uptake by phagocytes, and recruit phagocytes to sites of infection. Receptors for complement components and Fc receptors often synergize in activating the uptake and destruction of pathogens and immune complexes. Thus, the humoral immune response is targeted to the infecting pathogen through the production of specific antibody; however, the effector actions of that antibody are determined by its heavy-chain isotype.
Questions.
10.1 Multiple Choice: Which of the following is not an antibody effector function?
A. Opsonization
B. Neutralization
C. Complement activation
D. Linked recognition
E. NK-cell cytotoxicity
F. Mast-cell degranulation 10.2 Short Answer: The Haemophilus influenzae type b (Hib) vaccine was initially composed only of the polysaccharide capsule of the organism, but this failed to mount potent antibody responses. Directly conjugating the Hib polysaccharide to a tetanus or diphtheria toxoid, however, yielded very potent antibody responses to Hib, and is the current vaccine formulation. Indicate which immunological phenomenon is taken advantage of by conjugating the Hib capsule-derived polysaccharide to a toxoid, and how it works to elicit a potent antibody response.