The Best Australian Science Writing 2015 (24 page)

The immune system also does not provide most of the protection from chemical toxins (it helps, but the liver is charged with the bulk of that task, and the liver is not considered an organ of the immune system), so you've only got biological agents such as bacteria, parasites, and viruses – and their manifold secretions – to worry about. As you know, every inch of our surroundings is
swarming with billions of micro-organisms, constantly looking for a way in, so you need to take that into account. But it's not just infectious agents: for instance, immune reactions seek and destroy cells of the body's own that have gone bad. And you also can't just repel all outside invaders – the food we eat is readily accepted into our body, as is the oxygen we breathe. Every single one of us was, in the very beginning, a welcome visitor inside his or her mother's womb, so you need to plan for another human growing inside the body once in a while without the immune system going berserk and attacking it as the foreign body that it is. Not only that, but we constantly play willing hosts to trillions of bacteria, living mostly in our guts and on our skin. So the immune system you design must constantly be able to tell self from friend from fetus from foe.

It also needs to distinguish between foes. The creatures it needs to fend off are collectively known as
pathogens
(a combination of two Greek words, meaning ‘disease producers'), but they can be as different to one another as we are to them.
Bacteria
are microscopic, independent, single-celled organisms.
Protozoans
are also independent and single-celled, but they are actually much closer relatives of ours, which makes the job of distinguishing between our cells and theirs (and finding a way to kill them without harming the body too much) pretty hard.
Viruses
, on the other hand, aren't cells at all; they're essentially just clever bits of genetic material wrapped in a protein coating, and in order to breed they have to enter a host cell and take it over from the inside, forcing it to abandon its regular role and turning it into a virus-producing factory. Then you have multicellular parasites, such as intestinal worms, and fungal infections too, and to top it all off, there are the rogue cells of the human body itself that I mentioned, which have lost their inhibitions and decided to proliferate wildly – and if they succeed, they produce tumours.

The immune system cannot react to all of these in the same way, because they are very different creatures, found in different places, and must be dealt with by different methods. Bacteria wandering around in the blood or the lungs or wherever must be treated differently from viruses infecting a host cell, or from worms in our intestines, etc. The immune system is challenged with tailoring its response to each type of threat (a challenge shared by medical scientists who face the same problems when they seek treatments, vaccines, and cures for all these diseases).

And so, an immune system must correctly identify a diverse array of harmful creatures and react to each one in its own special way. Oh, and you know what would be very helpful? If it could remember the pathogens it's encountered before and store this information on file, somehow, so that it could make short work of them the next time they pop in. And it needs to be prepared for new invaders it's never encountered before, because life is like that. And it needs to be prepared for completely new invaders nobody has ever encountered before in the history of humankind, because pathogens evolve over time. And it needs to be economical, so the body can keep it operational. And it needs to be fairly unobtrusive, so the body can keep functioning normally. And it needs to do it all
very quickly
, every time, or the body will be overrun, because pathogens multiply like the devil.

All that, I hope you will agree while you jot down hasty sketches for your proposed design for an immune system and calculate a rough budget and personnel requirements for the project, is one seriously tall order. Indeed, the immune system we've got isn't perfect. Sometimes it fails, and we fall ill, and then we get better. Sometimes the challenge is too great, and we don't get better. Quite often, the immune system itself malfunctions or overreacts, and we suffer from problems known as
autoimmune disorders.
Nevertheless, most people, most of the time, live through a very large number of immune challenges – which
I think is remarkable. Isn't your immune system lovely? Give it an appreciative pat on the thymus, why don't you?

Elusive elements

You won't, though, will you? Because you don't know where the thymus is, or what it is exactly that it does, do you? There's no need to feel guilty. The immune system is a uniquely diffuse sort of thing, with organs and functions secreted away in odd corners of the body; it's no wonder it took so ridiculously long for us humans to notice that we even have one.

Think about it this way: if a heart stops functioning properly, medical science offers replacements in the shape of pacers and heart transplants. If your lungs collapse, you can be put on a respirator. Dialysis machines can do the work of your kidneys. Artificial limbs replace arms and legs. Hearing aids can help if your hearing isn't up to the task. We have glasses and corrective surgery for the eyes. We can transplant livers (although we don't really have an artificial substitute for this remarkable organ yet). And although the brain and the nervous system are currently nowhere near being replaceable, a surgeon can still take a scalpel and do some good even there.

But there is no mechanical way to fix or replace a nonworking immune system. We can give drugs and boosters and vaccines, but all these interventions must be processed by the immune system itself. We cannot replace or transplant any part of the immune system (with the notable exception of bonemarrow transplant, which is used in some specific cases). The only thing doctors can do to patients that doesn't enlist the help of the patients' own immune systems at all is to sterilise their entire surroundings.

The immune system is composed of numerous types of molecules, cells, tissues, and organs, spread throughout various locations in the body and maintaining complex relationships with
each other and with other systems of the body. Its executive arm constantly circulates throughout the body, on the lookout for any sign of trouble. I won't go into a detailed list of all its elements, but it would be instructive to witness the machine in action. Perhaps it would be interesting to try and experience it from the other side.

What the bug saw

For the start of our tour of the immune system, it may be fun to think of what it feels like from the point of view of an incoming pathogen. I'll need to temper that a bit, of course, because even if we could imagine how pathogens experience their environment (which we can't, as nothing in our daily lives prepares us for thinking like intestinal parasites), a micro-organism entering the body encounters an overwhelming battery of seemingly unrelated threats, all intent on its destruction. So I may stop along the way and explain what's going on. I'll also account for the various responses to the various types of pathogens. Let the games commence.

To start us off, let's join a bacterium as it first comes into contact with a potential human host. Most bacteria could not care less about humans; they don't bother us or bother with us. However, a small minority of bacterial species have become specialised in making a life for themselves in human tissues, and they are willing to face the challenges presented by their lifestyle for a chance at the bounty. For those that manage to overcome its defences, a human body provides extraordinarily rich takings – a virtually inexhaustible supply of food, warmth, stability, and anything a bacterium could ask for.

Bacteria can enter anywhere, but most likely the first point of contact would be the skin – which is technically considered a part of the immune system, as it provides a solid, multi-layered, generally very effective physical barrier. Many species of bacteria
stop there and either give up and die or manage to set up camp on the skin and live off the oils we exude, as well as any other nutrients they can find. Sometimes they're the cause of rashes and skin infections, but the normal state of your skin is that it is crawling with countless bacteria that do it no harm at all. The problem begins when the skin's integrity is breached – wounds, minor cuts, abrasions, insect bites, and burns provide infectious agents with a way into the body.

Another very popular method of entry is via the mouth. Some invaders make their way to the lungs and other parts of the respiratory system, while others try their luck among the thriving community of bacteria in the gut (which are known as the body's
microflora
or as
commensal bacteria
). Still others will try to infiltrate the body at one point or another along the mucosal (read: slimy) epithelial cells that line our digestive system.

Coming at it from the other end, some bacteria try to find a way in via the urogenital tract (cringe), which is a pretty dicey route to go, but one that does offer the advantage of a direct link between two human bodies. This is important to some pathogens (most famously the dreaded HIV virus) that die almost immediately upon exposure to fresh air, and thus have to wait for their host to engage in the inter-body docking manoeuvres that we call ‘sex' in order to pass to a new host.

It's a rough deal being a germ; their survival rate is abysmal. Precious few make it to their destination. The overwhelming majority die in the attempt: die by not coming into contact with a human host at all and ending up in the ground, on a wall, in the ocean, or in a handkerchief in somebody's pocket; die by exposure to unfavourable temperatures in the outside environment, or to nasty materials on the skin, or to the acids and digestive enzymes in the stomach and the intestines; die by the actions of other species of bacteria, which have zero regard for the wellbeing of the newcomers, and will compete with them for food
and sometimes actively attack them. Commensal bacteria in the gut will even snitch on pathogens to the body, sending chemical signals to the cells in the (human) gut lining that cause it to strengthen itself and make it harder to penetrate.

Those microbes that do not die can find themselves pushed away by the muscular workings of the gut, washed away by urine (if they're trying to climb up that way) or tears (in the eyes) or saliva (in the mouth), or bustled out of the way by cilia (tiny hairlike structures that function as a sort of bucket chain that dumps foreign matter out of the airways and the lungs).

The pathogen that finds itself still ready and wriggling after all this, poised to infiltrate the human body, would be quite justified in piping up and exhorting its fellow survivors with something along the lines of Henry V's rousing ‘we few, we happy few' speech to his army in Shakespeare's eponymous play. But microbes don't do that kind of thing, so it doesn't. Still, much like Henry V's army, the surviving bacteria's troubles are just beginning.

Having managed to penetrate the physical wall of epithelial cells, an invading microbe now immediately experiences the wrath of the
innate immune system,
a diverse barrage of cells and molecules, lovingly thrown together by evolution to rain destruction upon invaders in a variety of ways. From the pathogen's point of view, all hell breaks loose: enzymes and small antimicrobial peptide molecules try to eat away at the bacterium's outer layers; a group of proteins, known to us as the
complement system,
attaches to its surface and assembles there to form a gaping hole in its membrane (this hole is thus known by the impressive name of
membrane attack complex
). If it somehow gives these the slip, special bacteria-recognising proteins stick to its body, tagging it for consumption by several kinds of bacteria-gobbling cells – we call them
phagocytes –
which try to eat it up whole and then digest it with searing chemicals.

A type of phagocyte called a
macrophage
not only eats bacteria, but also secretes signal molecules that promote an
inflammatory response.
This has the effect of making blood vessels near the infection site more permeable, and also of recruiting other phagocytes to the spot. What this means for the bacteria is that there is suddenly even more nasty stuff intent on killing it. Cells are
literally crawling out of the walls
(the now-dilated blood vessels) and coming after it.

Viruses and assisted suicide

If the pathogen is a virus rather than a bacterium, it will do its best to infect a host cell and keep out of the way of the immune system, which may, in turn, identify the viral material and sound the alarm. Antiviral elements are then released; uninfected cells are cautioned to bolster their defences against viral intrusion, and cells that have already been infected are coaxed towards committing suicide – a natural process known as
programmed cell death
or
apoptosis.

The body works on the honour system: each cell is expected to signal if it has been infected or otherwise damaged beyond repair. Molecules called
MHC class I
, which are present on the outside of most cell types in the body, bind
peptides
– small bits and fragments of protein – and present them to the outside environment in a context that immune cells can understand. This means that when a cell in your body has been infected with a virus, it quickly displays a message to the immune system that says, in effect,
‘Help! Help! I'm infected! Tell me to kill myself now!' –
and the immune system is happy to oblige.

It is in the interest of the immune system to have infected cells self-destruct in such an orderly fashion, since a violent, explosive death will release the virus particles rather than destroy them – and we wouldn't want that. This system can sometimes be subverted by pathogens that infiltrate the cell and manage to
prevent it from hoisting the ‘infected' flag: the result is a problematic infectious disease. When it is subverted by a human cell whose self-control systems have gone haywire, this might be the start of a tumour.