Tuesday, 10 March 2009

What is the complement system?

The complement system is one of multicellular life’s ancient defences against pathogens.  It consists of about 30 proteins that engage in a rapidly-enhancing cascade of activation that occurs when incited by certain stimuli.

Remember that our immune systems can be broadly divided into the innate component and the adaptive component?  Complement is one of the major components of our innate immunity, although it can be activated by the adaptive component too.

Let’s take a closer look. Although there are many other proteins, the most important ones in complement are named C1 to C9. These proteins are happily gliding around in your blood stream as you read this, but unless you are in the midst of an infection, they are largely idle. To jump into action, what they need is the right stimulus. There are three types of “right stimulus”, which we’ll cover in more detail in the next post. They are the activators of the “classical pathway”, the “alternative pathway” and the “lecithin pathway”. 

A full diagram of all the interactions between the complement factors is cumbersome and pointless unless you’re an immunologist. However, I’ve found that this little schema is quite helpful.

As you can see, all three pathways converge on the cleavage of C3 into C3a and C3b. From then onwards, the result is the same, and here is where it begins to get interesting. Complement activation achieves three broad immunological goals:
  • Opsonisation – this refers to the process whereby foreign bodies are “labelled” to facilitate their phagocytosis.  This is the job of C3b.

  • Chemotaxis and mast cell activation – chemotactic stimuli are those that coax immune cells to migrate towards them.  Since they are given off at sites of inflammation, they cause immune cells to congregate where they are needed.  Mast cells are like little chemical warfare factories, ready to release a whole battery of violent chemicals when asked to.  In general, these promote inflammation – for instance by increasing vascular permeability, and by further promoting chemotaxis.  The jobs in this heading are accomplished by C3a and C5a.

  • Lysis of target cells – one of the most dramatic effects of complement activation is the formation of the “membrane attack complex” (MAC), utilizing C5b and C6 to C9.  The end result is a channel that punches a hole in the cell membrane of the doomed cells, allowing the free flow of substances between its intra- and extracellular components.  Because most foreign microbes pack their cells with solutes, there is an eternal osmotic pressure seeking to drive water into the cells.  Usually this has to be resisted by means of a cell wall (in addition to the cell membrane), but if the membrane attack complex goes to work, this is to no avail.  Sodium and water flood inward, causing the cell to first swell and then burst. 

That covers what complement is, and what it achieves. The next post will deal with the its three activation pathways.

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