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What Is the Complement System?

By H. Colledge
Updated Feb 01, 2024
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The complement system is part of the body's immune system and consists of a series of protein molecules which activate each other in a sequence known as a cascade. Complement system proteins are present in the blood stream and in the fluid that surrounds body tissues. When a pathogen such as a harmful microorganism enters the body, the complement system is triggered, and the proteins activate one another along one of three pathways. These are known as the classical complement pathway, the alternative complement pathway and the lectin pathway. Complement system activity coats pathogens so they are more easily targeted by the body's immune cells, and actively destroys those which are already attached to antibodies.

In the immune system, organs, tissues and cells work together to defend the body from harmful organisms and other substances that cause disease. The complement system forms part of what is called the innate immune system, which is present at birth. This differs from the adaptive immune system, which comes into play when a microbe is recognized after a previous attack.

The complement system can be activated when antibodies, which are proteins produced by cells in the immune system, bind to potentially harmful substances, or antigens. These antigens might be proteins present on the surface of a single-celled bacterium. When antibodies attach to antigens, this can activate the complement system's classical pathway. The lectin pathway and the alternative complement pathway are activated by different methods.

In the classical pathway, part of the first complement protein, known as C1, binds to the antibody attached to an antigen on the surface of a bacterium. This binding activates another part of C1, which becomes an enzyme capable of splitting in half the complement proteins known as C2 and C4. The active part of C4 then binds to the bacterial surface and the active part of C2 attaches to it. This combination of parts of C2 and C4 also acts as an enzyme, which breaks up the next complement protein, C3.

Part of C3 binds to the cell surface, making it more attractive to immune cells known as phagocytes, while some of it binds to C5, helping other complement proteins to activate it. C5 splits up and forms what is called the membrane attack complex together with C6, 7 and 8. The membrane attack complex enables C9 complement proteins to form a tube which creates a channel through the bacterial cell membrane. Water is drawn into the cell and it bursts, destroying the bacterium.

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Discussion Comments
By Mor — On Nov 13, 2011

@indigomoth - Unfortunately, there are all kinds of different reasons why your immune system can't be in hyperdrive all the time. For one thing, it takes energy to maintain it, as well as vitamins and so forth, and the systems that maintain it can wear out.

For another, a revved up immune system can make mistakes. The completary system is said to be involved in causing diseases as well as curing them. For example some forms of arthritis are caused by an overactive immune system. It might also be involved in Alzheimer's disease.

So it's not as simple as that, unfortunately.

By indigomoth — On Nov 12, 2011

I was reading an article the other day about the immune system and it said something which I found interesting.

Apparently that old chestnut about how you will always get sick in the holidays is actually based a little bit in fact.

While you are at work and feeling all stressed out, your immune system will kick into overdrive because of the stress. As far as your immune system knows, you're hunting or being chased, and you need to be as healthy as possible.

Then, the holidays come around and you relax from the stress. Boom. Your immune system also relaxes and suddenly bugs it might have been holding back are allowed to get a foothold in your system.

I don't see why the complement system and other immune system components can't just be on overdrive all the time.

By KoiwiGal — On Nov 12, 2011

We learned about the complement system in biology class.

Apparently they discovered it back in the 1800's. Someone realized that if you add blood serum (the liquid that blood cells are suspended in) to bacteria it can kill some of the bacteria.

Then, Jules Bordet discovered that there are two parts to the blood serum and that one of these parts can be "deactivated" by heating it and is generally good against most pathogens.

That part is the complementary system.

It was a few years later that Paul Ehrlich started calling it "complement" because it complemented the actions of the rest of the immune system.

It's pretty amazing that people back then were able to discover things like this without the aid of modern technology.

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