502 Chapter 15(see fig. 15.1 ). These and various cytokines promote the recruit-
ment of monocytes to the infection site, where they can adhere
to extracellular matrix proteins (chapter 6, section 6.1) and
transform into macrophages. Macrophages ingest microorgan-
isms and fragments of the extracellular matrix by phagocytosis;
they also release nitric oxide, which aids in the destruction of
bacteria. As neutrophils die by apoptosis, releasing more prote-
ases and other agents that contribute to the inflammation, their
remains are engulfed by macrophages. This phagocytosis of
apoptotic neutrophils then causes the macrophages to release
growth factors and other agents that help to end the inflamma-
tion and promote repair.
After some time, B lymphocytes are stimulated to produce
antibodies against specific antigens that are part of the invading
bacteria. Binding of these antibodies to antigens in the bacte-
ria greatly amplifies the previously nonspecific response. This
occurs because of greater activation of complement, which
directly destroys the bacteria and which also—together with
the antibodies themselves—promotes the phagocytic activity
of neutrophils, macrophages, and monocytes (see fig. 15.5 ).
The ability of antibodies to promote phagocytosis is called
opsonization.
These effects produce the characteristic symptoms of a local
inflammation: redness and warmth (due to histamine-stimulated
vasodilation); swelling (edema) and pus; and pain. These symp-
toms were first described by Celsus around 40 a.d. as “rubor,
calor, dolor, and tumor” (redness, heat, pain, and swelling,
respectively). The pain threshold is lowered by prostaglandin E 2
(PGE 2 ), released as a cytokine during inflammation. PGE 2 and
pain from inflammation is reduced by aspirin and other NSAIDs
(nonsteroidal anti-inflammatory drugs), which inhibit the cyclo-
oxygenase enzymes (COX-1 and COX-2) that produce prosta-
glandins (chapter 11, figure 11.34). If the infection continues,
the release of endogenous pyrogen from leukocytes and macro-
phages may also produce a fever, as previously discussed.
Inflammatory processes protect the body and are required
for health. However, these processes can also damage the body.
Even when the inflammation is triggered by pathogens, the
inflammation can sometimes inflict more harm than the patho-
gens themselves. Examples of diseases in which inflammation
plays an important pathogenic role include Alzheimer’s disease,
multiple sclerosis, atherosclerosis, asthma, rheumatoid arthritis,
systemic lupus erythematosus, and type 1 diabetes mellitus.proteins and bacterial products may serve as chemokines,
drawing the leukocytes toward the site of infection.
The leukocytes squeeze between adjacent endothelial cells
(the process of extravasation, discussed earlier) and enter the
subendothelial connective tissue. There, particular molecules
on the leukocyte membrane interact with surrounding mol-
ecules that guide the leukocytes to the infection. The first to
arrive are the neutrophils, followed by monocytes (which can
change into macrophages) and T lymphocytes ( fig. 15.6 ). Most
of the phagocytic leukocytes (neutrophils and monocytes)
die in the course of the infection, but lymphocytes can travel
through the lymphatic system and re-enter the circulation.
Resident macrophages and mast cells in the infected tis-
sue are activated by the binding of their pathogen recognition
receptors to the PAMPs (section 15.1) of the invading bacteria.
These resident macrophages and mast cells release chemicals
that attract neutrophils to the site of the infection; the neutro-
phils then release molecules that recruit circulating monocytes,
lymphocytes, and other immune cells to the infected area.
Neutrophils kill microoorganisms through phagocytosis
and the release of enzymes and a variety of antimicrobial pep-
tides. They also release NETs—neutrophil extracellular traps—
composed of extracellular fibers that trap invading pathogens.
The NETs immobilize the bacteria, facilitate their phagocyto-
sis, and may also kill them directly by means of antimicrobial
enzymes. Through the action of proteases (protein-digesting
enzymes), the neutrophils liquefy the surrounding tissues.
This produces a viscous, protein-rich fluid that, together with
dead neutrophils, forms pus. Pus can be beneficial because it
produces pressure that closes lymphatic and blood capillaries,
blocking the spread of bacteria away from the site of the battle.
The neutrophils also release granule proteins that are recog-
nized by monocytes rolling along the endothelium of capillariesFigure 15.6 Infiltration of an inflamed site by
leukocytes. Different types of leukocytes infiltrate the site
of a local inflammation. Neutrophils arrive first, followed by
monocytes and then lymphocytes.
See the Test Your Quantitative Ability section of the Review
Activities at the end of this chapter.
0 6 12 18 24
HoursLeukocyte infiltrationNeutrophilsMonocytesT lymphocytes30 36 42 48IntensityClinical Investigation CLUES
Timmy’s wound hurt and got red and swollen, and it
oozed some pus before it healed.- What processes made the wound red, swollen, and
painful? - What is pus, and how is it produced?