of the membrane attack complex. (para 2-8d)
21.
The primary activators of the alternative pathway are usually non-immunological in
nature. They include bacterial lipopolysaccharides, erythrocytes of certain
species, viruses, fungi, and parasites. Aggregated IgE, IgA, and IgG subclass 4
are immunological activators of this pathway. (para 2-9a)
22.
An initial requirement for activation of the alternative pathway is the presence of
C3b, which is continuously generated in small amounts by natural hydrolysis of
C3. Continuation of the alternative pathway occurs only if an activating surface is
present to provide a binding site for the C3b and protect it from control protein
activity. (para 2-9b)
23.
In the alternative pathway, in the presence of C3b, factor B is cleaved by factor D
into two fragments, Bb and Ba. The Bb fragment forms a complex with C3b and
the resultant C3b, Bb complex is known as C3 convertase. This complex has
enzymatic properties and is capable of cleaving and activating more C3.
Properdin (P) acts as a stabilizer for the C3b, Bb complex by protecting it from
decay and control mechanisms. Large amounts of C3b are generated and
resupply the reaction cycle. The C3b may release to the fluid phase as an
opsonin, bind directly to the activating surface, or attach to C3 convertase forming
the complex, C3b, Bb, 3b. This complex is known as C5 convertase and is
capable of cleaving and activating C5, the first component of the membrane attack
complex. (para 2-9c)
24.
The membrane attack complex (MAC), beginning with the cleavage and activation
of C5, is common to both complement pathways. The activation of C5 results in
two fragments. The smaller C5a fragment is released into the fluid phase as an
anaphylatoxin or chemotactic factor. The larger C5b fragment binds directly to the
activating surface, followed by the binding of C6 and C7 (Figure 2-7). The C5b67
complex provides a binding site for C8 which initiates some membrane damage.
However, the subsequent binding of multiple molecules of C9 is required for
efficient cell lysis. (para 2-10)
25.
There are control mechanisms in the complement system that preclude
uncontrolled activation and consumption of its protein components. For example,
binding sites on activated proteins decay rapidly, causing dissociation of
complexes. This restricts the complement activation to a local area. (para 2-11)
26.
Several substances are released to produce the biological effects of complement
activation.
For example, anaphylatoxins cause the release of histamine from mast cells and
basophils. Histamine in turn enhances vascular permeability and causes smooth
muscle contractions, resulting in edema and inflammation. Many cells, including
polymorphonuclear cells, B lymphocytes, and macrophages, have receptor sites
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