Defense Mechanisms of the Body
651
As described in Chapter 12, the vasodilation and increased
permeability to protein, however, cause net fi ltration of plasma
into the interstitial fl uid and the development of edema. This
accounts for the swelling in an infl amed area, which is simply a
consequence of the changes in the microcirculation and has no
known adaptive value of its own.
Chemotaxis
With the onset of infl ammation, circulating neutrophils begin
to move out of the blood across the endothelium of capillaries
and venules to enter the infl amed area. This multistage process
is known as
chemotaxis.
It involves a variety of protein and car-
bohydrate
adhesion molecules
on both the endothelial cell and
the neutrophil. It is regulated by messenger molecules released
by cells in the injured area, including the endothelial cells. These
messengers are collectively called
chemoattractants
(also
called
chemotaxins
or chemotactic factors).
In the fi rst stage, the neutrophil is loosely tethered to
the endothelial cells by certain adhesion molecules. This
event, known as
margination,
occurs as the neutrophil rolls
along the vessel surface. In essence, this initial reversible event
exposes the neutrophil to chemoattractants being released in
the injured area. These chemoattractants act on the neutro-
phil to induce the rapid appearance of another class of adhe-
sion molecules in its plasma membrane—molecules that bind
tightly to their matching molecules in the endothelial cells.
Thus, the neutrophils collect along the site of injury, rather
than being washed away with the fl owing blood.
In the next stage, known as
diapedesis,
a narrow projec-
tion of the neutrophil is inserted into the space between two
endothelial cells, and the entire neutrophil squeezes through
the endothelial wall and into the interstitial fl
uid. In this way,
huge numbers of neutrophils migrate into the infl
amed area.
Once in the interstitial fl uid, neutrophils migrate toward the
site of tissue damage (chemotaxis). This occurs because dam-
aged cells release chemoattractants. Thus, neutrophils tend to
move toward the microbes that entered into an injured area.
Movement of leukocytes from the blood into the dam-
aged area is not limited to neutrophils. Monocytes follow
later, and once in the tissue they undergo anatomical and
functional changes that transform them to macrophages. As
we will see later, in specifi c immune defenses lymphocytes
undergo chemotaxis, as can basophils and eosinophils under
certain conditions.
An important aspect of the multistep chemotaxis process
is that it provides selectivity and fl exibility for the migration of
the various leukocyte types. Multiple adhesion molecules that
are relatively distinct for the different leukocytes are controlled
by different sets of chemoattractants. Particularly important in
this regard are those cytokines that function as chemoattrac-
tants for distinct subsets of leukocytes. For example, one type
of cytokine stimulates the chemotaxis of neutrophils, whereas
another stimulates that of eosinophils. Thus, subsets of leu-
kocytes can be stimulated to enter particular tissues at desig-
nated times during an infl ammatory response, depending on
the type of invader and the cytokine response it induces. The
various cytokines that have chemoattractant actions are col-
lectively referred to as
chemokines.
Killing by Phagocytes
Once neutrophils and other leukocytes arrive at the site of an
injury, they begin the process of destroying invading microbes
by phagocytosis. The initial step in phagocytosis is contact
between the surfaces of the phagocyte and microbe (
Figure
18–1
). One of the major triggers for phagocytosis during this
contact is the interaction of phagocyte receptors with certain
Table 18–4
Some Important Local Infl
ammatory Mediators
Mediator
Source
Kinins
Generated from enzymatic action on plasma proteins
Complement
Generated from enzymatic action on plasma proteins
Products of blood clotting
Generated from enzymatic action on plasma proteins
Histamine
Secreted by mast cells and injured cells
Eicosanoids
Secreted by many cell types
Platelet-activating factor
Secreted by many cell types
Cytokines, including chemokines
Secreted by injured cells, monocytes, macrophages, neutrophils, lymphocytes, and several
nonimmune cell types, including endothelial cells and fi broblasts
Lysosomal enzymes, nitric oxide,
and other oxygen-derived substances
Secreted by injured cells, neutrophils, and macrophages
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