C h a p t e r 1 5
Innate and Adaptive Immunity
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complement system, including enhanced inflammatory
responses, increased phagocytosis, and destruction and
clearance of the pathogen from the body, make it an inte-
gral component of innate immunity and inflammation.
Role of Innate Immunity in
Stimulating Adaptive Immunity
In addition to its role as a first-line defense in recog-
nizing microbes and preventing infections, the innate
immune response generates molecules that function as
“second signals” together with antigens to activate the
adaptive immune response. Full activation of antigen-specific B and T lymphocytes requires two signals.
Antigen provides the first signal. Microbes, the response
of the innate immune system to microbes, and host cells
damaged by microbes all may provide the second sig-
nal. This requirement for a second microbe-initiated sig-
nal ensures that lymphocytes respond to microbes (the
natural inducers of innate immunity) and not to harm-
less noninfectious substances. For the purpose of induc-
ing immunity through vaccination, adaptive immune
responses may be induced by antigens without microbes.
In such instances, the antigens have to be administered
with substances called
adjuvants
that elicit the same
adaptive immune reactions as microbes do.
The second signals that are necessary for activa-
tion of the adaptive immune system can be generated
by antigen-presenting dendritic cells and macrophages
or by activation of the complement system. Microbes
that breach the epithelial barriers of the innate immune
system stimulate dendritic cells and macrophages to
produce two types of second signals that activate T lym-
phocytes. First, the dendritic cells and macrophages
express surface molecules called
co-stimulators
, which
bind to receptors on naive T cells and function together
with antigen recognition to activate T cells. Second, the
dendritic cells and macrophages secrete cytokines that
stimulate the differentiation of naive T cells into effector
cells of cell-mediated adaptive immunity. Blood-borne
microbes activate the complement system by the alter-
native pathway. One of the proteins produced by the
complement system becomes covalently attached to the
microbe, producing a second signal for activation of
B lymphocytes.
Adaptive Immunity
The adaptive immune system is able to distinguish
among different, even closely related, microbes and
molecules and to “remember” the pathogen by quickly
producing a heightened immune response on subse-
quent encounters with the same agent. The components
of the adaptive immune system are lymphocytes and
their products. Foreign substances that elicit specific
responses are called
antigens.
There are two types of adaptive immune responses:
humoral and cell-mediated immunity.
Humoral immu-
nity
is mediated by secreted molecules and is the prin-
cipal defense against extracellular microbes and toxins.
Cell-mediated immunity,
or
cellular immunity,
is medi-
ated by specific T lymphocytes and defends against
intracellular microbes such as viruses.
Antigens
Before discussing the cells and responses inherent to
adaptive immunity, it is important to understand the
substances that elicit a response from the host.
Antigens,
also called
immunogens,
are substances foreign to the
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The effector responses of innate immunity involve
viral destruction by natural killer (NK) cells,
phagocytosis of microbes by neutrophils and
monocytes, initiation of the inflammatory response,
and recruitment of the complement system.
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Development of innate immunity and regulation
of effector cells depends on the secretion of
soluble mediators, such as opsonins, cytokines,
and acute-phase proteins. Opsonins bind to and
tag microorganisms for more efficient recognition
by phagocytes. Cytokines released from activated
leukocytes regulate the activity of other cells,
amplify inflammation, stimulate the production of
acute-phase proteins, and aid in the initiation of
an adaptive immune response.
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The complement system, which is a primary
effector system for both the innate and adaptive
immune systems, consists of a group of proteins
that are activated by microbes and promote
inflammation and destruction of the microbes.
Recognition of microbes by complement occurs
in three ways: by the classical pathway, an
adaptive immune pathway which recognizes
antibody bound to the surface of a microbe or
other structure; by the lectin pathway, an innate
pathway which uses a plasma protein called the
mannose-binding ligand that binds to mannose
residues on microbial glycoproteins or glycolipids;
and by the alternative pathway, an innate pathway
which recognizes certain microbial molecules.
SUMMARY CONCEPTS
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Innate immunity consists of the physical, cellular,
chemical, and molecular defenses that are ready
for activation and mediate rapid initial protection
against infectious agents. Epithelial cells of the
skin and mucous membranes, which are the
first line of defense, block the entry of infectious
agents and secrete antimicrobial molecules that
can effectively kill a wide variety of microbes.
