Chapter 116. Immunization Principles and Vaccine Use (Part 3)

The Immune Response While many constituents of infectious microorganisms and their products (e.g., exotoxins) are or can be rendered immunogenic, only some stimulate protective immune responses that can prevent infection and/or clinical illness or (as in the case of rotavirus) can attenuate illness, providing protection against severe disease but not against infection or mild illness. The immune system is complex, and many factors—including antigen composition and presentation as well as host characteristics—are critical for stimulation of the desired immune responses (Chap. 308).The Primary ResponseThe primary response to a vaccine antigen includes an apparent latent period of several days before...
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Chapter 116. Immunization Principles and Vaccine Use (Part 3) Chapter 116. Immunization Principles and Vaccine Use (Part 3) The Immune Response While many constituents of infectious microorganisms and their products(e.g., exotoxins) are or can be rendered immunogenic, only some stimulateprotective immune responses that can prevent infection and/or clinical illness or(as in the case of rotavirus) can attenuate illness, providing protection againstsevere disease but not against infection or mild illness. The immune system iscomplex, and many factors—including antigen composition and presentation aswell as host characteristics—are critical for stimulation of the desired immuneresponses (Chap. 308). The Primary Response The primary response to a vaccine antigen includes an apparent latentperiod of several days before immune responses can be detected. Although theimmune system is rapidly activated, it takes 7–10 days for activated Blymphocytes to produce enough antibody to be detected in the circulation. Theprimarily IgM antibodies seen initially are rapidly produced but have only a lowaffinity for the antigen. After the first week, high-affinity IgG antibodies begin tobe produced in quantity; this switch from IgM to IgG production requires theparticipation of CD4+ T-helper lymphocytes—the middle men of the immuneresponse. Because precursors for T cells mature within the thymus gland, antigensthat stimulate T cells are referred to as T or thymus-dependent antigens.Circulating antigen-specific T lymphocytes that implement cell-mediated immuneresponses are identified in the peripheral bloodstream only after several days butbegin to increase in number immediately after antigenic stimulation. Activation of these responses typically requires co-recognition of theantigen by specific molecular species of HLA, the major histocompatibilitycomplex, which is present on the surface of lymphocytes and macrophages. Someindividuals cannot respond to one or more antigens, even when repeatedlyexposed, because they do not have the genes for the particular HLA type involvedin antigen recognition, processing, and presentation for an immune response. Thissituation is known as primary vaccine failure. The Secondary Response Stronger and faster humoral or cell-mediated responses are elicited by asecond exposure to the same antigen and are detectable within days of thebooster dose. The secondary response depends on immunologic memoryinduced by the primary exposure and is characterized by a marked proliferation ofIgG antibody–producing B lymphocytes and/or effector T cells. Purepolysaccharide antigens, such as the first-generation pneumococcal vaccine, evokeimmune responses that are independent of T cells and are not enhanced byrepeated administration. However, conjugation of the same polysaccharide to asuitable protein converts the carbohydrate antigen into one that is T cell–dependent and able to induce immunologic memory and secondary responses toreexposure. Although levels of vaccine-induced antibodies may decline over time,revaccination or infection generally elicits a rapid (anamnestic) protectivesecondary response consisting of IgG antibodies, with little or no detectable IgM.Thus, a lack of measurable antibody in an immunized individual does notnecessarily indicate secondary vaccine failure. Similarly, the mere presence ofdetectable antibodies after immunization does not ensure clinical protection: thelevel of circulating antibody may need to exceed a threshold value in order tomediate protection (e.g., 0.01 IU/mL for tetanus antitoxin). Mucosal Immunity Some pathogens are confined to and replicate only at mucosal surfaces(e.g., Vibrio cholerae), whereas others first encounter the host at a mucosal surfacebefore they invade systemically (e.g., influenza virus). A distinctiveimmunoglobulin, secretory IgA, is produced at mucosal surfaces and is adapted toresist degradation and to function at these sites. Vaccines may be specificallydesigned to induce secretory IgA and thereby to block the essential initial steps indisease pathogenesis that occur on mucosal surfaces. Given its complexity,mucosal immunology has become a separate branch of the field of immunology. Measurement of the Immune Response Immune responses to vaccines are often gauged by the concentration ofspecific antibody in serum. Although seroconversion (i.e., transition fromantibody-negative to antibody-positive status) serves as a dependable indicator ofan immune response, it does not necessarily correlate with protection unless serumantibody is the critical mechanism in vivo and the levels achieved are sufficient(e.g., against measles). ...