Page 555 - Review of Medical Microbiology and Immunology ( PDFDrive )

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PART VII Immunology
544
(1) C1 inhibitor is an important regulator of the classic
cially Neisseria species are very susceptible. Cytolysis is
pathway. It inactivates the protease activity of C1. Activa-
not an enzymatic process; rather, it appears that insertion
tion of the classic pathway proceeds past this point by
generating sufficient C1 to overwhelm the inhibitor.
of the complex results in disruption of the membrane and
(2) Regulation of the alternative pathway is mediated by
the entry of water and electrolytes into the cell.
the binding of factor H to C3b and cleavage of this complex
by factor I, a protease. This reduces the amount of C5 con-
vertase available. The alternative pathway can proceed past
The binding of C3b to its receptors on the surface of acti-
this regulatory point if sufficient C3b attaches to cell mem- Enhancement of Antibody Production
vated B cells greatly enhances antibody production com-
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branes. Attachment of C3b to cell membranes protects it
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pared with that by B cells that are activated by antigen
from degradation by factors H and I. Another component
alone. The clinical importance of this is that patients who
that enhances activation of the alternative pathway is pro-
perdin, which protects C3b and stabilizes the C3
than do those with normal amounts of C3b. The low con-
convertase.
centration of both antibody and C3b significantly impairs
(3) Protection of human cells from lysis by the mem-
host defenses, resulting in multiple, severe pyogenic
brane attack complex of complement is mediated by decay-
infections.
accelerating factor (DAF, CD55)—a glycoprotein located
on the surface of human cells. DAF acts by binding to C3b
and C4b and limiting the formation of C3 convertase and
CLINICAL ASPECTS OF
C5 convertase. This prevents the formation of the mem-
COMPLEMENT
brane attack complex.
(1) Inherited (or acquired) deficiency of some com-
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plement components, especially C5–C8, greatly enhances
BIOLOGIC EFFECTS OF
susceptibility to Neisseria bacteremia and other infec-
COMPLEMENT
tions. A deficiency of MBL also predisposes to severe
Opsonization
recurrent pyogenic sinus and respiratory tract
Microbes, such as bacteria and viruses, are phagocytized
infections.
much better in the presence of C3b because there are C3b
(2) Inherited deficiency of C1 esterase inhibitor
receptors on the surface of many phagocytes.
results in angioedema. When the amount of inhibitor is
reduced, an overproduction of esterase occurs. This leads
Chemotaxis
permeability and edema.
C5a and the C5,6,7 complex attract neutrophils. They
(3) Acquired deficiency of decay-accelerating factor on
migrate especially well toward C5a. C5a also enhances the to an increase in anaphylatoxins, which cause capillary
the surface of cells results in an increase in complement-
adhesiveness of neutrophils to the endothelium.
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mediated hemolysis. Clinically, this appears as the disorder
paroxysmal nocturnal hemoglobinuria (see Chapter 68).
Anaphylatoxin
(4) In transfusion mismatches (e.g., when type A blood is
C3a, C4a, and C5a cause degranulation of mast cells with
body to the A antigen in the recipient binds to A antigen on
release of mediators (e.g., histamine), leading to increased
the donor red cells, complement is activated, and large
vascular permeability and smooth muscle contraction,
amounts of anaphylatoxins and membrane attack complexes
especially contraction of the bronchioles leading to bron-
are generated. The anaphylatoxins cause shock, and the
chospasm. Anaphylatoxins can also bind directly to smooth
membrane attack complexes cause red cell hemolysis.
muscle cells of the bronchioles and cause bronchospasm.
(5) Immune complexes bind complement, and thus
C5a is, by far, the most potent of these anaphylatoxins.
Anaphylaxis caused by these complement components is
(e.g., acute glomerulonephritis and systemic lupus erythe-
less common than anaphylaxis caused by type I (IgE-
matosus). Binding (activating) complement attracts poly-
mediated) hypersensitivity (see Chapter 65). complement levels are low in immune complex diseases
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morphonuclear leukocytes, which release enzymes that
damage tissue.
Cytolysis
(6) Patients with severe liver disease (e.g., alcoholic cir-
Insertion of the C5b,6,7,8,9 membrane attack complex
(MAC) into the cell membrane forms a “pore” in the
liver function and therefore cannot synthesize sufficient
membrane. This opening in the membrane results in the
complement proteins, are predisposed to infections caused
killing (lysis) of many types of cells, including erythrocytes,
by pyogenic bacteria.
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