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UNIT IV
Infection, Inflammation, and Immunity
Key Points
INNATE IMMUNITY
•
Innate immunity consists of physical, chemical,
cellular, and molecular defenses that are ready
for activation and mediate rapid, initial protection
against infection.
•
The effector responses of innate immunity involve
the inflammatory process and phagocytosis by
cells that express pattern recognition receptors
(PRRs) that bind with broad patterns shared by
groups of microbes but not present on mammalian
cells. Toll-like receptors, a major type of PRR, are
expressed on phagocytes and are potent activa-
tors of innate immune system cells and molecules.
Epithelial Barriers
Physical, mechanical, and biochemical barriers against micro-
bial invasion are found in all common portals of entry into the
body, including the skin and respiratory, gastrointestinal, and
urogenital tracts. The intact skin is by far the most formidable
physical barrier available to infection because of its design. It
is comprised of closely packed cells that are organized in mul-
tiple layers that are continuously shed. In addition, a protective
layer of protein, known as keratin, covers the skin. The skin
has simple chemicals that create a nonspecific, salty, acidic
environment and antibacterial proteins, such as the enzyme
lysozyme, that inhibit the colonization of microorganisms and
aid in their destruction. The complexity of the skin becomes
evident in cases of contact dermatitis where increased suscep-
tibility to cutaneous infection occurs as the result of abnor-
malities of the innate immune response including defects in
the epithelial layer itself and defects in both signaling and or
expression of innate responses.
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Sheets of tightly packed epithelial cells line and pro-
tect the gastrointestinal, respiratory, and urogenital tracts and
physically prevent microorganisms from entering the body.
These cells destroy the invading organisms by secreting anti-
microbial enzymes, proteins, and peptides. Specialized cells
in these linings, such as the goblet cells in the gastrointestinal
tract, secrete a viscous material comprised of high molecular
weight glycoproteins known as mucins, which when hydrated
form
mucus
. The mucins bind to pathogens, thereby trapping
them and washing away potential invaders. In the lower respi-
ratory tract, hairlike, mobile structures called
cilia
protrude
through the epithelial cells and move microbes trapped in the
mucus up the tracheobronchial tree and toward the throat. The
physiologic responses of coughing and sneezing further aid in
their removal from the body.
Microorganisms that are trapped by mucus are then
subjected to various chemical defenses present throughout
the body. Lysozyme is a hydrolytic enzyme found in tears,
INNATE IMMUNITY
After completing this section of the chapter, you should
be able to meet the following objectives:
••
Understand the recognition systems for pathogens in
innate immunity.
••
Describe the functions of the various cytokines
involved in innate immunity.
••
Define the role of the complement system in immu-
nity and inflammation.
The innate immune system is comprised of two separate
but interrelated lines of defense: the epithelial layer, which
acts as a physical barrier to invading substances and organ-
isms, and the inflammatory response. The innate immune
response utilizes the body’s natural epithelial barriers
along with phagocytic cells (mainly neutrophils and mac-
rophages), natural killer (NK) cells, and several plasma
proteins, including kinins, clotting factors, and those of
the complement system, to maintain internal homeostasis.
The innate immune response relies on the body’s ability to
distinguish evolutionarily conserved structures on patho-
gens known as PAMPs from structures on human cells.
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The response of the innate immune system is rapid, usu-
ally within minutes to hours, and prevents the establishment
of infection and deeper tissue penetration of microorgan-
isms. The innate immune response is usually very effective
against most pathogens. However, when the innate response
is overwhelmed, adaptive immune responses become acti-
vated as the final line of defense against invading organisms.
Innate immune mechanisms are always present in the body
before an encounter with an infectious agent and are rap-
idly activated by microorganisms and foreign substances.
Therefore, the body’s defenses are in full swing before the
development of the adaptive immune response. The innate
immune system also interacts with and directs adaptive
immune responses.
Under normal conditions, the innate immune response is
essential to the continued health and well-being of the body.
However, during times of hyperresponsiveness or hypore-
sponsiveness, the innate immune system plays a role in the
pathogenesis of disease. One of the main functions of the
innate immune system is the initiation of the inflammatory
response, which involves the activation of a complex cas-
cade of events and chemical mediators. As part of the innate
immune response, inflammation plays a key role in the patho-
genesis of many common pathophysiologic states includ-
ing atherosclerosis and coronary artery disease, bronchial
asthma, non–insulin-dependent diabetes mellitus (NIDDM),
rheumatoid arthritis, multiple sclerosis, and systemic lupus
erythematosus.
