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The Complement System


Sometimes the interaction of antibodies with antigen is useful by itself. For example, But most of the time, the binding of antibodies to antigen performs no useful function until and unless it can activate an effector mechanism. The complement system serves several effector roles.


Features of the system

The Classical Pathway

The binding of antibody to its antigen often triggers the complement system through the so-called classical pathway. It can occur in solution or — as shown here — when the antibodies have bound to antigens on a cell surface.

The proteins of the classical pathway


C1 exists in blood serum as a molecular complex containing: The constant regions of mu chains (IgM) and some gamma chains (IgG) contain a binding site for C1q. A single molecule of IgM is enough to initiate the pathway. IgG is far less efficient, requiring several molecules to do so (6 is the optimum — the same as the number of C1q molecules in C1).
(Over a decade ago, complement workers decided that the smaller of all C fragments should be designated with an "a", the larger with a "b". This required changing the existing nomenclature for C2. That is why you will find the C3 convertase designated C4b•2a in older literature.)


C3 is the most abundant protein of the complement system (~1.3 mg/ml). Because of its abundance and its ability to activate itself (by a mechanism described below), it greatly magnifies the response.


Cleavage of C5 by the C3/C5 convertase initiates the assembly of a set of complement proteins that make up the membrane attack complex. (The membrane attack complex can also be formed by another C5 convertase produce by the "alternative pathway" [Link].)

The Membrane Attack Complex

Cleavage of C5 by the C3/C5 convertase, produces:

The electron micrograph (courtesy of Drs. J. H. Humphrey and R. Dourmashkin) shows holes punched through the cell wall of the Gram-negative bacterium Shigella dysenteriae by the terminal components of the complement system. (Some of the holes are larger than expected for C9 channels and probably were enlarged later by the action of lysozyme.)

Summary: Effector Functions of Complement

Cell lysis is only one function (and probably not the most important one) of the complement system. The complement system acts in several ways to mobilize defense mechanisms.

The Alternative Pathway

The complement system can also be triggered without antigen-antibody complexes. Even in their absence, there is a spontaneous conversion of C3 to C3b. Ordinarily the C3b is quickly inactivated: the C3b binds to inhibitory proteins and sialic acid present on the surface of the body's own cells, and the process is aborted.

However, bacteria and other foreign materials that may get into the body lack these proteins and have little or no sialic acid. So the C3b

Regulation of Complement Activity

The explosive potential of the complement system requires that it be kept under tight control. At least 12 proteins are known that do this. Three examples:

Disorders of the Complement System

With so many proteins involved, it is not surprising that inherited deficiencies of one or another are sometimes encountered in humans.
Five examples:
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17 March 2020