C h a p t e r 1 5
Innate and Adaptive Immunity
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Innate Immunity
The innate immune system consists of the epithelial bar-
riers; phagocytic neutrophils, macrophages, dendritic
cells, NK cells; and several plasma proteins, including
those of the complement system. These mechanisms are
present in the body before an encounter with an infec-
tious agent and are rapidly activated by microbes before
the development of adaptive immunity. The innate
immune system also interacts with and directs adaptive
immune responses.
With the ever-expanding wealth of information
on immune system function, it is becoming clear that
the innate immune system not only protects against
microbial agents, but may also play a role in the patho-
genesis of disease. Among the functions of the innate
immune system is induction of a complex cascade of
events known as the
inflammatory response
(discussed
in Chapter 3). Recent evidence suggests that low-grade
inflammation and activation of the innate immune sys-
tem play a key role in the pathogenesis of a number of
disorders, such as atherosclerosis and coronary artery
disease, bronchial asthma, type 2 diabetes mellitus,
rheumatoid arthritis, multiple sclerosis, and systemic
lupus erythematosus.
Epithelial Barriers
Our outer body surfaces are protected by epithelia,
which provide physical and chemical barriers between
the internal environment and the pathogens of the
external world. Epithelia include the epidermis of the
skin and linings of the respiratory, gastrointestinal, and
urogenital tracts. The intact skin is a formidable physi-
cal barrier because of its closely packed cells, multiple
layers, continuous shedding of cells, and presence of
the protective protein keratin. In addition to its barrier
function, the skin has chemicals that create a salty and
acidic environment, and antibacterial proteins, such as
the enzyme lysozyme, that inhibit the colonization of
microorganisms and aid in their destruction.
The mucous membrane linings of the gastrointesti-
nal, respiratory, and urogenital tracts are protected by
sheets of tightly packed epithelial cells that block the
entry of microbes and destroy them by secreting anti-
microbial enzymes, proteins, and peptides. Specialized
cells in these linings secrete a viscous material called
mucus.
Mucus traps and washes away microorganisms,
especially with the help of additional secretions such
as saliva. Also in the lower respiratory tract, hairlike
structures called
cilia
protrude through the epithelial
cells. The synchronous action of the cilia moves many
microbes trapped in the mucus toward the throat. The
physiologic responses of coughing and sneezing further
aid in their removal from the body.
Once microbes are trapped, various chemical defenses
come into play. These include lysozyme, a hydrolytic
enzyme capable of cleaving the walls of bacterial cells;
complement, which binds and aggregates bacteria to
increase their susceptibility to phagocytosis or disrupt
their lipid membrane; and members of the
collectin
fam-
ily of surfactant proteins (e.g., surfactants [SP]-A and
SP-D) in the respiratory tract (see Chapter 21). The
best-defined function of the surfactants is their ability to
opsonize pathogens, including bacteria and viruses, and
to facilitate phagocytosis by innate immune cells such
as macrophages. In the stomach and intestines, death of
microbes results from the action of digestive enzymes,
acidic conditions, and secretions of
defensins,
small cat-
ionic peptides that rapidly kill many types of bacteria by
disrupting their membrane.
Cells of Innate Immunity
Some pathogens can penetrate the epithelial barriers
of the host and cause infection, particularly when the
barrier has been breached as in wounds, burns, or loss
of the body’s internal epithelia. The subsequent innate
immune response to the penetration of these invaders is
initiated by several types of immune cells with receptors
for recognition of general groups of microbes. The key
cells of innate immunity include phagocytic leukocytes
and NK cells.
Several types of phagocytic leukocytes recognize
and kill infectious agents during an innate immune
response. The early-responding phagocytic cell is the
neutrophil
, followed shortly by the more efficient,
that react to a unique antigen, can distinguish self
from nonself, and develop immunologic memory,
allowing a prompt and heightened response on
subsequent encounters with the same antigen.
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The cellular components of innate and adaptive
immunity include the phagocytic cells that are of
myeloid lineage and the lymphocytes that are of
lymphoid lineage.The phagocytic granulocytes,
macrophages, and dendritic cells, along with
the natural killer (NK) cells, participate in innate
immune responses, and the B andT lymphocytes
participate in adaptive immune responses.
■■
The tissues of the immune system consist of the
generative or central lymphoid organs in which
B andT lymphocytes originate and mature and
the peripheral lymphoid organs in which adaptive
immune responses to microbes is initiated.
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Cytokines are soluble proteins secreted by cells
of both the innate and adaptive immune systems
that mediate many of the functions of these
cells. Some cytokines mediate inflammation
or interfere with viral replication. Chemokines
are cytokines that stimulate the migration and
activation of immune and inflammatory cells.
Colony-stimulating factors are cytokines that
stimulate the growth and differentiation of bone
marrow progenitors of immune cells.
