Defense Mechanisms of the Body
way, multiple active complement proteins are generated in the
extracellular fl
uid of the infected area from inactive comple-
ment molecules that have entered from the blood. Because this
system consists of at least 30 distinct proteins, it is extremely
complex, and we will identify the roles of only a few of the
individual complement proteins.
Five of the active proteins generated in the complement
cascade form a multiunit protein called the
membrane attack
complex (MAC).
The MAC embeds itself in the microbial
plasma membrane and forms porelike channels in the mem-
brane, making it leaky. Water and salts enter the microbe,
which disrupts the intracellular ionic environment and kills
the microbe.
In addition to supplying a means for direct killing of
microbes, the complement system serves other important
functions in infl
ammation (
Figure 18–4
). Some of the acti-
vated complement molecules along the cascade cause, either
directly or indirectly (by stimulating the release of other
ammatory mediators), vasodilation, increased microves-
sel permeability to protein, and chemotaxis. Also, one of the
complement molecules—
—acts as an opsonin to attach
the phagocyte to the microbe (
Figure 18–5
As we will see later, antibodies, a class of proteins
secreted by lymphocytes, are required to activate the very fi rst
complement protein (C1) in the full sequence known as the
classical complement pathway. However, lymphocytes are not
involved in
infl ammation, our present topic. How,
then, is the complement sequence initiated during nonspe-
cifi c infl ammation? The answer is that there is an
complement pathway,
one that is not antibody-dependent
and that bypasses C1. The alternate pathway is initiated as the
result of interactions between carbohydrates on the surface of
the microbes and inactive complement molecules beyond C1.
These interactions lead to the formation of active C3b, the
opsonin described in the previous paragraph, and the activa-
tion of the subsequent complement molecules in the pathway.
However, not all microbes have a surface conducive to initiat-
ing the alternate pathway.
Figure 18–3
Role of phagocytes in nonspecifi c immune defenses. Hormonal regulation of overall bodily responses to infection, partly addressed in Chapter 11,
will also be discussed later in this chapter.
Contact of phagocytes with microbes
Secretion of chemicals by phagocytes
Regulation of
killing of
killing of
Activation of clotting
and anticlotting
(Chapter 12)
regulation of
overall bodily
responses to
Activated complement proteins
Enhancement of
Vasodilation and increased
permeability of capillaries
and venules to proteins
Direct destruction of
invading microbes by
membrane attack complex
Figure 18–4
Functions of complement proteins. The effects on blood vessels and chemotaxis are exerted both directly by complement molecules and
indirectly via other infl ammatory mediators (for example, histamine) that are released by the complement molecules.
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