Activated complement components affect the inflammatory and immune response
in the following manner:
a. Increased vascular permeability.
b. Smooth muscle contraction.
Mast cell and basophil degranulation with the subsequent release of
d. Neutrophil activation and chemotaxis.
e. Enhanced opsonization and phagocytosis.
Lysis of target cells, bacteria, and viruses.
Many of these effects are due to complement cleavage products known as
anaphylatoxins. A related term is anaphylaxis, which is used to refer to an
exaggerated allergic reaction. (para 2-7)
Activators of the classical pathway are primarily antigen-antibody complexes or
aggregated immunoglobulins. Activators of the classical pathway include the IgG
subclasses IgG1, IgG2, and IgG3, but the most effective activator is the large
pentamer IgM. Nonimmunologic activators of this pathway include DNA, C-
reactive protein, certain cellular membranes, and trypsin-like enzymes.(para 2-8a)
Activation of the classical pathway begins with the interaction of C1 with an
antigen-antibody complex. The C1 component is comprised of three distinct
protein molecules: C1q, C1r, and C1s. The binding of the C1q component to the
Fc portion of the IgG or IgM molecule initiates the pathway. Changes in C1q
causes C1r to enzymatically activate C1s. (para 2-8b)
In the classical pathway, activated C1s cleave C4 into two fragments: C4a which is
released into the fluid phase as an anaphylatoxin and C4b which may bind directly
to the activating surface. C4b may also be released into the fluid phase as an
opsonin. Activated C1 also is capable of cleaving and activating C2 generating
C2a and C2b. A site on the C2a fragment allows it to bind to the surface-bound
C4b to form the complex C4b2a. (para 2-8c)
In the classical pathway, the C4b2a complex is known as C3 convertase and is
capable of cleaving and activating C3. C3a is the smaller of the two fragments
produced and is released into the fluid phase as an anaphylatoxin. A small
portion of the total number of C3b molecules bind to the activating surface and
interact with C4b2a. The resulting C4b2a3b complex is known as C5 convertase
and is capable of cleaving and activating C5. This is the first step to the formation