The Complement System

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Illustration shows an invading pathogen with an antigen on its surface. In the classic pathway for complement activation, host antibodies bind the antigen, and C 1 binds the antibody. The C 1-antibody complex causes C 2 and C 4 each to split in two. Fragments from C 2 and C 4 each joins together to form an enzyme called C 3 convertase. C 3convertase splits C 3 in two. One of the fragments from C 3 joins C 3 convertase to form C 5 convertase. C 5 convertase splits C 5 in two. A fragment from C 5 joins C 6, C 7, C 8, and C 9 to form a complex that makes a hole in the plasma membrane for the invading cell. The cell swells and bursts. In the alternative pathway, C 3 convertase spontaneously splits C 3 in two and the rest of the pathway proceeds the same as the classic pathway. Host cells are protected from complement by the presence of endogenous proteins.
The classic pathway for the complement cascade involves the attachment of several initial complement proteins to an antibody-bound pathogen followed by rapid activation and binding of many more complement proteins and the creation of destructive pores in the microbial cell envelope and cell wall. The alternate pathway does not involve antibody activation. Rather, C3 convertase spontaneously breaks down C3. Endogenous regulatory proteins prevent the complement complex from binding to host cells. Pathogens lacking these regulatory proteins are lysed. (credit: modification of work by NIH)

OpenStax Biology 2e

An array of approximately 20 types of soluble proteins, called a complement system, functions to destroy extracellular pathogens. Cells of the liver and macrophages synthesize complement proteins continuously; these proteins are abundant in the blood serum and are capable of responding immediately to infecting microorganisms. The complement system is so named because it is complementary to the antibody response of the adaptive immune system. Complement proteins bind to the surfaces of microorganisms and are particularly attracted to pathogens that are already bound by antibodies. Binding of complement proteins occurs in a specific and highly regulated sequence, with each successive protein being activated by cleavage and/or structural changes induced upon binding of the preceding protein(s). After the first few complement proteins bind, a cascade of sequential binding events follows in which the pathogen rapidly becomes coated in complement proteins.

Complement proteins perform several functions. The proteins serve as a marker to indicate the presence of a pathogen to phagocytic cells, such as macrophages and B cells, and enhance engulfment; this process is called opsonization. Certain complement proteins can combine to form attack complexes that open pores in microbial cell membranes. These structures destroy pathogens by causing their contents to leak.


Clark, M., Douglas, M., Choi, J. Biology 2e. Houston, Texas: OpenStax. Access for free at:



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