SNHS Biology Blog 11: The Complement System

Eric Liu

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When you think of the immune system, what comes to mind? T-Cells, antibodies, phagocytes? All these parts would not be able to do their jobs without another often-overlooked system – the complement system. Formed from over thirty-five unique proteins in the blood, the complement system assists the innate immune system in eliminating threats before you even realize that you are infected. Without it, your immune system would have almost no time to react to an infection before it got out of hand, making the complement system a vital part of your body’s intricate defense system.

The complement system, like many systems in biology, is extraordinarily complex. In fact, the complement system has three different activation pathways. Thankfully, however, all three seek to begin the same activation pathway – one that will form a membrane attack complex (more on that later). The classical activation pathway begins when antibodies bind to antigens, forming immune complexes that activate complement proteins. In contrast to this is the alternative pathway, which involves the natural cleavage and activation of C3, the first protein in the activation pathway, due to the presence of pathogens. Finally, the lectin pathway begins with complement proteins binding to the glycoproteins present on bacterial cell membranes and beginning the biochemical cascade. Already, the complexity of just a section of the immune system is stunning.

Ultimately, each of the pathways seek to cleave the C3 protein into C3a and C3b. It is here that the complement system begins its job as a member of the immune system. C3a travels far away from the infection site, activating the body’s innate defensive cells, the neutrophils, monocytes, and macrophages. The greater the concentration of C3a, the more aggressive the phagocytes become. However, it is C3b that does the bulk of the work. C3b seeks out and attaches to pathogens, changing its shape and setting off the activation pathway of many different proteins. These proteins assist the immune system by marking targets, clearing immune complexes, neutralizing viruses, and tagging along with follicular dendritic cells to activate B-cells, the body’s antibody factories. The C3b protein has remained firmed anchored on the surface of bacteria all this time, and it is now ready to go on the offensive. Cleaving C5 into C5b and C5a, C3b assists in the creation of a quaternary protein structure within the bacterial membrane called a membrane attack complex, or MAC. Such a structure punctures a hole into the cell membrane, causing the bacteria to lyse and die.

The complement system demonstrates just how effective individual proteins can be when they are used together in a massive chain reaction. For all the praise that phagocytes and lymphocytes in defending the body, it is important not to forget the role the complement system plays in keeping you alive and well.