Clone Wars – What Happens When You Get A Splinter In Your Toe?

biohazard sign

For the last two years or so, I’ve been crunching some numbers on the genetics of T cells together with colleagues from the Dept. of Bacteriology and Immunology at the Haartman Institute, Helsinki. It has turned out that with the help of high-throughput sequencing and the resulting massive amounts of data, immunology is an enormous unexplored playground for complex-systems scientists; I’ve had plenty of fun and we’re currently writing up the results of this first stretch. There are all sorts of marvels out there, and yes, there be power laws too.  I’ll write a series of posts on the topic. To whet your appetite, here’s a small story:

Ever wondered what happens in your body when you get a splinter in your toe?

Here’s a summary. The splinter breaches your first line of defence – your skin – and intruders follow. Once they are in, your so-called innate immune system responds. This response has to be swift; bacteria multiply quickly. Many things happen: the chemicals of the so-called complement system start drilling holes into bacterial cell walls. Macrophages, big eater cells, devour any invaders they meet. They become increasingly vicious and release cytokines, chemicals that call other types of cells to arms. Cytokines also increase the permeability of your blood vessels: that’s why your toe will swell. Now neutrophils that circulate in your blood will exit and follow the scent of battle. Once at the front line, they release a cargo of toxic chemicals, killing invaders. When done, they die and become pus.

The battle rages on. New kinds of soldiers become involved. One class – dendrite cells – picks up some battle debris and quietly exits the front lines. Now things will escalate. Dendrite cells travel to the lymph nodes, where an enormous repertoire of T and B cells awaits. Each has a different type of receptor on their surface, waiting to be triggered. Dendrite cells keep on displaying their cargo – bits of dead bacteria – until a matching receptor is found. When this happens, the cell hosting the receptor begins to proliferate, producing a massive army of clones.

Next comes the decisive strike. The clone army enters battle, armed with homing devices targeted at the specific type of invader. B cells begin to sprout and release receptors, producing enormous amounts of antibodies that find the invaders, coat their surfaces, and mark them for destruction by macrophages and other killers. T cells enter the front line, directing the battle, releasing more cytokines, and making sure that all bactericidal cells are fully engaged in battle. All weapons of the immune system are now deployed: the invader is being hit from all directions.

With all likelihood, the invader will now yield. It cannot hold against the combined response of the innate and the adaptive system. The battle winds down. T-cells command the foot soldiers to disengage, macrophages clear the battlefield of wreckage, blood vessels no longer leak fluid. Neutrophils stop pouring out of the blood stream; they move on and look for signs of new trouble elsewhere. Pain, redness, and swelling will cease.

If the invader ever returns, it is dealt with swiftly, without you even noticing. This is because your body remembers the invader: some of the B and T cells that saw battle have become memory cells that can quickly mount an overwhelming defence.

But with many bacteria and viruses, evolution runs fast. Next time you meet them, they might have changed already; your body has won one battle but will be at war forever.

Coming up next: how your immune system does gradient-descent Monte Carlo with zillions of threads in parallel, starting from a massive repertoire of initial conditions.

(In the meantime, if you want a longer, detailed version of the above story, see “How the Immune System Works” by Lauren M. Sompayrac; it’s a textbook that even those of us who don’t have much biomedical background can follow).



2 thoughts on “Clone Wars – What Happens When You Get A Splinter In Your Toe?

  1. Pingback: Thou Shalt Not Smooth! – Jari Saramäki

  2. Pingback: Do an MSc in Complex Systems – Admission Now Open! – Jari Saramäki

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