Page 553 - Review of Medical Microbiology and Immunology ( PDFDrive )

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mebooksfree.com mebooksfree.com mebooksfree.com mebooksfree.com H A P mebooksfree.com mebooksfree.com
63
C
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Complement

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mebooksfree.com mebooksfree.com mebooksfree.com Clinical Aspects of Complement mebooksfree.com mebooksfree.com

CHAPTER C ONTENT S

Introduction
Anaphylatoxin
Cytolysis
Activation of Complement
Regulation of the Complement System
Enhancement of Antibody Production
Biologic Effects of Complement
Opsonization
Self-Assessment Questions
Practice Questions: USMLE & Course Examinations
Chemotaxis

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mebooksfree.com mebooksfree.com mebooksfree.com central molecule of the complement cascade. The presence mebooksfree.com
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INTRODUCTION
All three pathways lead to the production of C3b, the
The complement system consists of approximately 20
of C3b on the surface of a microbe marks it as foreign and
proteins that are present in normal human (and other
targets it for destruction. C3b has two important functions:
animal) serum. The term complement refers to the ability
(1) It combines with other complement components to
of these proteins to complement (i.e., augment) the effects
generate C5 convertase, the enzyme that leads to the pro-
of other components of the immune system (e.g., anti-
duction of the membrane attack complex; and (2) it opso-
body). Complement is an important component of our
nizes bacteria because phagocytes have receptors for C3b
innate host defenses.
on their surface.
There are three main effects of complement: (1) lysis of
1
(1) In the classic pathway, antigen–antibody complexes
cells such as bacteria, allografts, and tumor cells; (2) gen-
2
eration of mediators that participate in inflammation and
form a C4b,2b complex. The latter is C3 convertase, which
attract neutrophils; and (3) opsonization (i.e., enhance- activate C1 to form a protease, which cleaves C2 and C4 to
cleaves C3 molecules into two fragments, C3a and C3b. C3a,
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mebooksfree.com mebooksfree.com mebooksfree.com (C4b,2b,3b), which cleaves C5 to form C5a and C5b. C5a is mebooksfree.com
ment of phagocytosis). Complement proteins are synthe-
an anaphylatoxin, is discussed later. C3b forms a complex
sized mainly by the liver.
with C4b,2b, producing a new enzyme, C5 convertase
an anaphylatoxin and a chemotactic factor (see later). C5b
ACTIVATION OF COMPLEMENT
binds to C6 and C7 to form a complex that interacts with C8
and C9 to produce the membrane attack complex
Several complement components are proenzymes, which
(C5b,6,7,8,9), which causes cytolysis. Note that the “b” frag-
must be cleaved to form active enzymes. Activation of the
ment continues in the main pathway, whereas the “a” frag-
complement system can be initiated either by antigen–
ment is split off and has other activities.
antibody complexes or by a variety of nonimmunologic
molecules (e.g., endotoxin).
Sequential activation of complement components
(Figure 63–1) occurs via one of three pathways: the classic 1 complement; however, activation by IgG requires two cross-linked IgG
Only IgM and IgG fix complement. One molecule of IgM can activate
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pathway, the lectin pathway, and the alternative pathway
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mebooksfree.com mebooksfree.com mebooksfree.com 2 of 18 polypeptides that binds to the Fc portion of IgG and IgM. It is multi- mebooksfree.com
molecules. C1 is bound to a site located in the Fc region of the heavy
(see later). Of these pathways, the lectin and the alterna-
chain. Of the IgGs, only IgG1, IgG2, and IgG3 subclasses fix complement;
tive pathways are more important the first time we are
IgG4 does not.
infected by a microorganism because the antibody required
C1 is composed of three proteins, C1q, C1r, and C1s. C1q is an aggregate
to trigger the classic pathway is not present. The lectin
valent and can cross-link several immunoglobulin molecules. C1 is a pro-
pathway and the alternative pathway are, therefore, partici-
enzyme that is cleaved to form an active protease. Calcium is required for
pants in the innate arm of the immune system.
the activation of C1.
542
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