What is the complement system?

Be sure at the outset to get your mind around the idea that the complement system is a set of over 20 different protein molecules always found in the blood. There are no cells in the system. With an infection, this system of molecules is activated, leading to a sequence of events on the surface of the pathogen that helps destroy the pathogen and eliminate the infection.

How is the complement system activated?

The complement system can be activated in two main ways. The first means of activation is part of the innate (natural) immune response. (i.e.; neither antibodies nor T cell receptors are involved.) For example, certain polysaccharides found on the surface of bacteria can activate the system. This can occur immediately and does not require prior exposure to the molecules.

The second and most potent means occurs in a specific immune response when antibodies (IgG or IgM) binds to antigen at the surface of a cell. This exposes the Fc region of the antibody in a way that allows the first complement protein (C1) to bind.

What happens as a result of the activation?

But in either case, a cascade of events follows, in which each step leads to the next. At the center of the cascade are steps in which the proteolysis of a complement protein leads to a smaller protein and a peptide. The smaller protein remainds bound to the complex at the surface of the microorganism, while the peptide diffuses away.

Refer to the figure to the right. Notice how complement C3 is cleaved into C3b and C3a. C3b remains bound to the complex at the surface of the microorganism. This not only activates the next step, but also C3b is a good opsonin. The small peptide, C3a diffuses away and acts as a chemotactic factor and an inflammatory paracrine.

Next, complement protein C5 is cleaved into C5b and C5a. The C5b remains bound to complex on the surface of the cell while the C5a diffuses away and acts much like C3a.

Then the complement proteins C6, C7, and C8 bind successively to the growing complex. Finally, a number of C9 complement proteins bind to the complex. These C9 proteins are elongated molecules that form a circle with a large hole in the middle. This structure, which is called a membrane attack complex (MAC), pierces the membrane of the cell. This initiates a sequence of event leading to lysis (of a microbe) or apoptosis (of a cell of the body in pathologies and tissue transplants).

Thus the complement system triggers a constellation of effects that helps deal with an infection:

Quick Quiz

Fill in Answer Correct False Correct Answer
Name a molecule that activates the complement system as part of a specific immune response.
Name a component of the activated complement system that serves as a good opsonin.
Name a component of the activated complement system that promotes general inflammation
Which type of immunity triggers the complement system via polysaccharides without any prior exposure?

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