Section III. COMPLEMENT
Complement is a system of serum proteins that is the primary dissolved
mediator of antigen-antibody reactions. The complement system plays an integral role
in the basic defense mechanisms of the body. It is a complex series of enzymatic
proteins occurring in normal serum which interact to enhance the immune response.
a. In normal individuals, the complement system enables the body to respond in
several ways to infections: production of anaphylatoxins which contract smooth muscle
and increase vascular permeability and cause edema, production of chemotactic agents
which cause an influx of leukocytes, and facilitation of phagocytosis by which infective
agents are consumed and destroyed. Opsonization is the term for rendering bacteria
and other cells susceptible to phagocytosis.
b. The system involves the sequential activation and interaction of at least 14
serum proteins and may occur via the classical pathway or the alternative pathway.
These two pathways are parallel but independent. However, the two pathways do
become identical at the point of the membrane attack complex. Natural inhibitors and
instability of the complexes act to balance the system so that uncontrolled activation
does not occur. Thus, total consumption of the components does not occur every time
there is activation.
c. The key step in these pathways is the cleavage of C3. C3a promotes
inflammatory changes useful for fighting infection. C3b promotes adherence of
phagocytes and continuation of the alternative pathway. The alternative pathway is
notable because it can be activated without an antibody reaction.
d. One way to appreciate the importance of the complement system is to
observe what happens in those rare individuals with hereditary deficiencies of the
classical pathway. These individuals are predominantly ill with a variety of diseases and
repeated infections, including Neisseria organisms.
ROLES OF COMPLEMENT
a. Activated complement components affect the inflammatory and immune
response in the following manner:
Increased vascular permeability.
Smooth muscle contraction.
Mast cell and basophil degranulation with the subsequent release of