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U N I T 4
Infection and Immunity
the infected cell and are displayed on the target cell’s
surface, where they are recognized by antigen receptors
on the cytotoxic T cell (see Fig. 15-12). Cytotoxic T cells
perform their killing function by releasing preformed
cytotoxic proteins that induce apoptosis or programmed
cell death of the target cell (see Chapter 2).
The principal function of CD4
+
cells of the T
H
1 sub-
set involves the defense against intracellular pathogens,
such as mycobacteria, which grow primarily in phago-
somes of macrophages, shielding them from the effects
of both antibodies and cytotoxic T cells. These cells
secrete the cytokine IFN-
γ
, a potent macrophage acti-
vator, which stimulates the induction of microbicidal
substances in macrophages, leading to the destruction
of the ingested microbes. CD4
+
T
H
1 cells also produce a
range of other cytokines, chemokines, and surface mol-
ecules that do not activate infected macrophages, but
instead kill chronically infected senescent macrophages,
stimulate the production of new macrophages in bone
marrow, and recruit fresh macrophages to sites of infec-
tion. Thus, the CD4
+
T
H
1 cell controls and coordinates
host defenses against certain intracellular pathogens, a
function that helps to explain why a decreased CD4
+
T
H
1 count in persons with acquired immunodeficiency
syndrome (AIDS) places them at high risk for intracel-
lular pathogen infections.
Active Versus Passive Immunity
Adaptive, or specific, immune responses are designed
to protect the body against potentially harmful foreign
substances, infections, and other sources of non–self
antigens. It is the specific protection that is acquired
through exposure to antigens (active immunity) or
through transfer of protective antibodies against an
antigen (passive immunity).
Active immunity
is acquired through immunization
or actually having a disease. It is called
active immu-
nity
because it depends on a response to the antigen by
the person’s immune system. Active immunity, although
long lasting once established, requires a few days to
weeks after a first exposure before the immune response
is sufficiently developed to contribute to the destruction
of the pathogen. However, the immune system usually
is able to react within hours to subsequent exposure to
the same agent because of the presence of memory B and
T lymphocytes and circulating antibodies. The process
of acquiring the ability to respond to an antigen after its
administration by vaccine is known as
immunization.
An acquired immune response can improve on repeated
exposures to an injected antigen or a natural infection.
Passive immunity
is immunity transferred from
another source. An infant receives passive immunity
naturally from the transfer of antibodies from its mother
in utero and through breast milk. Maternal IgG crosses
the placenta and protects the newborn during the first
few months of life. Normally, an infant has few infec-
tious diseases during the first 3 to 6 months owing to
the protection provided by the mother’s antibodies.
Passive immunity also can be artificially provided by the
transfer of antibodies produced by other people or ani-
mals. Some protection against infectious disease can be
provided by the injection of hyperimmune serum, which
contains high concentrations of antibodies for a specific
disease, or immune serum or gamma globulin, which
contains a pool of antibodies from many individuals
providing protection against many infectious agents.
Passive immunity produces only short-term protection
that lasts weeks to months.
Regulation of the Immune
Response
Self-regulation is an essential property of the immune
system. An inadequate immune response may lead to
immunodeficiency, but an inappropriate or excessive
response may lead to conditions varying from allergic
reactions to autoimmune diseases. This regulation is not
well understood and involves all aspects of the immune
response—antigen, antibody, cytokines, regulatory T
cells, and the neuroendocrine system.
With each exposure to antigen, the immune systemmust
determine the branch of the immune system to be activated
and the extent and duration of the immune response.
After exposure to an antigen, the immune response to
that antigen develops after a brief lag, reaches a peak, and
then recedes. Normal immune responses are self-limited
because the response eliminates the antigen, and the prod-
ucts of the response, such as cytokines and antibodies, have
a limited life span and are secreted only for brief periods
after antigen recognition. Evidence suggests that cytokine
feedback from the helper T or regulatory T cells controls
several aspects of the immune response.
Another facet of immune self-regulation is inhibition
of immune responses by tolerance. The term
tolerance
is used to define the ability of the immune system to be
nonreactive to self-antigens while producing immunity
to foreign agents. Tolerance to self-antigens protects
an individual from harmful autoimmune reactions (see
Chapter 16). Exposure of an individual to foreign anti-
gens may lead to tolerance and the inability to respond
to potential pathogens that cause infection. Tolerance
exists not only to self-tissues but also to maternal–fetal
tissues. Special regulation of the immune system is evi-
dent in privileged sites such as the brain, testes, ovaries,
and eyes. Immune damage in these areas could result in
serious consequences to the individual and the species.
SUMMARY CONCEPTS
■■
The adaptive immune response involves
a complex series of interactions between
components of the immune system and the
antigens of a foreign pathogen. It is able to
distinguish between self and nonself, recognize
and specifically react to large numbers of
