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Immunology
Adaptive immunity
Third Line of Defense:
If a microorganism overwhelms the body’s natural resistance, a third line of defensive
resistance exists. Acquired, or adaptive, immunity is a more recently evolved mechanism that
allows the body to recognize, remember, and respond to a specific stimulus, an antigen.
Adaptive immunity can result in the elimination of microorganisms and recovery from disease
and the host often acquires a specific immunologic memory. This condition of memory or recall
(acquired resistance) allows the host to respond more effectively if reinfection with the same
microorganism occurs. Adaptive immunity, as with natural immunity, is composed of cellular
and humoral components. The major cellular component of acquired immunity is the
lymphocyte; the major humoral component is the antibody. Lymphocytes selectively respond to
nonself-materials (antigens), which leads to immune memory and a permanently altered pattern
of response or adaptation to the environment.
Antibody-Mediated Immunity
Antibody synthesis typically involves the cooperation of three cells: antigen presenting cells
(e.g., dendritic cells and macrophages), helper T cells, and B cells. After processing by an
antigen-presenting cell, fragments of antigen appear on the surface of that cell in association
with class II MHC proteins. The antigen–class II MHC protein complex binds to receptors on
the surface of a helper T cell specific for that antigen. This activates the helper T cells to
produce interleukins such as interleukin-2 (IL-2), IL-4, and IL-5. These interleukins activate the
B cell to produce antibodies specific for that antigen. The activated B cell proliferates and
differentiates to form many plasma cells that secrete large amounts of immunoglobulins
(antibodies).
Although antibody formation usually involves helper T cells, certain antigens (e.g., bacterial
polysaccharides) can activate B cells directly, without the help of T cells, and are called T-cell–
independent antigens. In this T-cell–independent response, only IgM is produced by B cells
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Immunology
As depicted in Figure 57–3, B cells can perform two important functions during the induction
process: (1) they recognize antigens with their surface IgM that acts as an antigen receptor (2)
they present epitopes to helper T cells in association with class II MHC proteins. Note that the
IgM antigen receptor on the B cell can recognize not only foreign proteins but also
carbohydrates, lipids, DNA, RNA, and other types of molecules. The class II MHC proteins of
the B cell, however, can only present peptide fragments to the helper T cells. This distinction
will become important when haptens are discussed later in this chapter. It is this remarkable
ability of the IgM antigen receptor on the B cell to bind to an incredibly broad range of
molecules that enables B cells to produce antibodies against virtually every molecule known.
Cell-Mediated Immunity
In the following example, a bacterium (e.g., Mycobacterium tuberculosis) enters the body and
is ingested by a macrophage. The bacterium is broken down, and fragments of it called antigens
or epitopes appear on the surface of the macrophage in association with class II major
histocompatibility complex (MHC) proteins. The antigen–class II MHC protein complex
interacts with an antigen-specific receptor on the surface of a helper T lymphocyte. Activation
and clonal proliferation of this antigen-specific helper T cell occur as a result of the production
of interleukins, the most important of which are interleukin-2 (T cell growth factor) and gamma
interferon (activates macrophages). These activated helper T cells, aided by activated
macrophages, mediate one important component of cellular immunity (i.e., a delayed
hypersensitivity reaction specifically against M. tuberculosis).
Cytotoxic (cytolytic) T lymphocytes are also specific effectors of the cellular immune
response, particularly against virus-infected cells. In this example, a virus (e.g., influenza virus)
is inhaled and infects a cell of the respiratory tract. Viral envelope glycoproteins appear on the
surface of the infected cell in association with class I MHC proteins. A cytotoxic T cell binds
via its antigen-specific receptor to the viral antigen–class I MHC protein complex and is
stimulated to grow into a clone of cells by interleukin-2 produced by helper T cells. These
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Immunology
cytotoxic T cells specifically kill influenza virus–infected cells (and not cells infected by other
viruses) by recognizing viral antigen–class I MHC protein complexes on the cell surface and
releasing perforins that destroy the membrane of the infected cell.
FIGURE 57–2 Overview of the process by which cell-mediated immunity and antibodymediated immunity are induced by exposure to a virus. Note that the figure shows a virus as the
immunogen in the top left corner, but the same processes occur for other microbes, such as
bacteria or fungi. IL, interleukin; MHC, major histocompatibility complex. (Modified and
reproduced with permission from Stites D, Terr A, Parslow T, eds. Basic & Clinical
Immunology. 9th ed. Originally published by Appleton & Lange. Copyright 1997 McGrawHill.)
Active and passive immunity.
Active immunity can be acquired by natural exposure in response to an infection or natural
series of infections, or through intentional injection of an antigen. The latter, vaccination, is an
effective method of stimulating antibody production and memory (acquired resistance) without
contracting the disease. Suspensions of antigenic materials used for immunization may be of
animal or plant origin. These products may consist of living suspensions of weak or attenuated
cells or viruses, killed cells or viruses, or extracted bacterial products (e.g., altered and no
longer poisonous toxoids used to immunize against diphtheria and tetanus). The selected agents
should stimulate the production of antibodies without clinical signs and symptoms of disease in
an immunocompetent host (host is able to recognize a foreign antigen and build specific
antigen-directed antibodies) and result in permanent antigenic memory. Booster vaccinations
may be needed in some cases to expand the pool of memory cells. Artificial passive immunity
is achieved by the infusion of serum or plasma containing high concentrations of antibody or
lymphocytes from an actively immunized individual. Passive immunity via pre-formed
antibodies in serum provides immediate, temporary antibody protection against microorganisms
(e.g., hepatitis A) by administering preformed antibodies. The recipient will benefit only
temporarily from passive immunity for as long as the antibodies persist in the circulation.
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Immunology
Immune antibodies are usually of the IgG type with a half-life of 23 days. In addition, passive
immunity can be acquired naturally by the fetus through the transfer of antibodies by the
maternal placental circulation in utero during the last 3 months of pregnancy. Maternal
antibodies are also transferred to the newborn after birth. The amount and specificity of
maternal antibodies depend on the mother’s immune status to infectious diseases that she has
experienced. Passively acquired immunity in newborns is only temporary because it starts to
decrease after the first several weeks or months after birth. Breast milk, especially the thick
yellowish milk (colostrum), produced for a few days after the birth of a baby is very rich in
antibodies. However, for a newborn to have lasting protection, active immunity must occur.
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