496 Chapter 15
extravasation (or diapedesis ), is illustrated in figure 15.1.
Unlike fluid movement out of vessels, which occurs across
the walls of blood capillaries (chapter 14, fig. 14.9), leuko-
cytes leave through the walls of postcapillary venules. These
narrowest venules consist only of endothelial cells and sur-
rounding supporting cells. The leukocytes can penetrate the
endothelial layer within several minutes, but may be held up
by the basement membrane—a highly cross-linked network
of glycoproteins supporting the endothelial cells—for up to
a half hour before they can enter the surrounding connective
tissue.
Phagocytic cells have membrane receptors for microbial
molecules, as well as for antibodies (in a process called opso-
nization, discussed in section 15.2) and complement proteins
(see fig. 15.10 ) on the surface of pathogens, which trigger
phagocytosis. The phagocyte “eats” the microbe (by anal-
ogy with the way an amoeba eats) by engulfing it with cyto-
plasm, so that the microbe is internalized. The microbe thereby
becomes surrounded by a membrane derived from the plasma
membrane ( fig. 15.2 ) and is contained within a vacuole. This
vacuole then fuses with a lysosome, which contains digestive
enzymes. However, the lysosomal enzymes may be released
before the fusion is complete, killing the cell and contributing
to the inflammation of the infected area.
Cells of our own body that commit suicide (apoptosis—
chapter 3, section 3.5) signal macrophages to attack by dis-
playing a phospholipid molecule ( phosphatidylserine ) on their
surface that normally is found only on the inner layer of the
plasma membrane. The phosphatidylserine provides an “eat
me” signal to macrophages. However, unlike the activation of
phagocytes in response to foreign pathogens, other inflamma-
tory processes are suppressed when macrophages eat apoptotic
body cells. This limits the “collateral damage” that would oth-
erwise occur as a result of the inflammation.Most of the time, macrophages operate separately from the
immune system as they perform the simple service of clearing
cellular debris, such as the remnants of cells that die normally
from apoptosis. However, when they recognize pathogenic
signals through the activation of their toll-like receptors, they
become activated to secrete pro-inflammatory cytokines. Some
of these attract resident neutrophils and monocytes within con-
nective tissues, which are recruited to the site of an infection
by a process called chemotaxis— movement toward chemical
attractants. The chemical attractants are a subclass of cytokines
known as chemokines. Neutrophils are the first to arrive at the
site of an infection; monocytes arrive later and can be trans-
formed into macrophages as the battle progresses.
If the infection has spread, new phagocytic cells from the
blood may join those already in the connective tissue. These
new neutrophils and monocytes are able to squeeze through
the tiny gaps between adjacent endothelial cells in the ves-
sel wall and enter the connective tissues. This process, called
Figure 15.1 Stages involved in the
migration of white blood cells from blood
vessels into tissues. The figure depicts
a neutrophil that goes through the stages of
rolling, capture, adhesion and activation, and
finally extravasation (diapedesis) through the
blood vessel wall. This process is set in motion
when the invading bacteria secrete certain
chemicals, which attract and activate the white
blood cells. The steps of extravasation require
the binding of particular molecules on the white
blood cell surface to receptor molecules on the
surface of endothelial cells.
Adhesion
and activationCaptureRollingNeutrophilPhagocytosis of bacteriaExtravasationVessel wallSpreadingBacteriaPhagocyte Location
Neutrophils Blood and all tissues
Monocytes Blood
Tissue macrophages
(histiocytes)All tissues (including spleen, lymph
nodes, bone marrow)
Kupffer cells Liver
Alveolar macrophages Lungs
Microglia Central nervous systemTable 15.2 | Phagocytic Cells and Their
Locations