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Systems of the Human Body

The Complement System

The Complement System is a part of our immune system. C3 and C4 are proteins produced by the immune system to fight infection. If your C3 and C4 levels are low then it means that the immune system is actively trying to kill something. In a healthy person this means that there's an infection, but in someone with lupus, the immune system is trying to kill cells in the body. Doctors will try to stop the immune response by giving the patient steroids, methotrexate, and/or other immunosuppressants.

In the immune system there is something called the "Complement Cascade." This is a sequential immune reaction that can be started by antibodies or by bacterial molecules. In the complement cascade that is triggered by antibodies, what happens is the antibodies bind to something they think is foreign. When multiple antibodies have bound, a protein floating around in the blood recognizes the antibodies and grabs on to them. This protein is called C1 (for complement 1).

Once C1 binds another protein in the blood, C4 sees it and grabs on to C1. When it does this part of C4 gets chopped off, and it floats away. C4 has to be cut in two, or it doesn't work. Think of it as taking the sheath off of a knife. Once C4 has been cut, C2 recognizes it, binds, and is also cut. This C4/C2 combination can then cut C3, which is a major player in the complement cascade. When C3 is cut, part of it stays with C4/C2, but the part that floats away tells the immune system that there's a problem and the immune system had better get activated. The rest of the complement cascade is just a sequence of proteins being bound, cut, and binding more proteins. The order is C5, C6, C7, C8 and then finally C9. When C9 binds to the cell that the original antibodies grabbed on to, it punches a hole in the cell, which causes the cell to die.

Since C4 is an early protein in the complement cascade and C3 is important in both the complement reaction itself and in activating the immune system, these are used as markers of an immune response. If you are not fighting anything, your levels of C3 and C4 should be steady. If your immune system is fighting something (which often means cells in your body if you have lupus) then C3 and C4 get used up binding to cells and trying to kill them and the levels in your blood drop. This is why the C3 and C4 test is used to measure whether the immune system is active or not.