The field of immunology is moving forward at a furious rate — any immunology book that was written only five years ago is already dated.
The blood-brain barrier that blocks infectious pathogens from entering the brain via the bloodstream was supposed to be the physical barrier keeping the immune system out of the brain.
However, in the last 15 years or so, it's been realised that not only does the immune system interact with the brain, but also there's an entire class of brain cells — known as microglia — that are a type of macrophage (a white blood cell) whose role is to keep the brain clean of infection and cellular debris, and to promote neuronal repair when healing. They may also be a significant player in Alzheimer's disease.
Proteins which were previously thought to be just immune proteins are now popping up with additional roles: modulating synapse formation and pruning in the brain during the brain's developmental stage in early years.
Researchers now suspect that dysfunction of these proteins may be a contributing factor to conditions such as autism and schizophrenia. Could these be caused by an immune deficiency?
Neural receptors for pain recognise danger in the same way as immune cells, and co-ordinate their response with the immune system, increasing the inflammatory reaction even before there's any actual call for an immune reaction — the nervous system senses pain and damage and is smart enough to prepare the body for a probable infection in the near future.
We now know and appreciate the multitude of regulatory relationships that exist between components of the immune system — or systems — and also between it and elements outside of it. We see loose threads that only hint at the possible extent of association and integration between the immune system and the rest of our body — and beyond.
Like the connection between dietary fibre, the bugs that live in our gut, and autoimmune disease.
Bugs in the system
Dietary fibre does interesting things like lower your cholesterol, but one of its main effects is on our intestinal microbiota, which metabolise it for their own nutritional needs. The amount of fibre we eat has quite an effect on these micro-organisms that have co-evolved with us over all these many years; they, in turn, appear to have quite an effect on us.
When we change the composition of the food that comes rolling down into the gut to be high in fat and sugar and low in fibre, we also change the composition of our microflora. We're depriving our traditional, indigenous gut microbes of their nutrition and giving an advantage to those types of micro-organisms that are better at using concentrated fats and sugars.
In the last few years, researchers have been discovering that this imbalance has a significant effect on our immune system. There's been a flurry of papers showing how a good diet, high in fibre and low in fat, has a dramatic protective effect on virtually all immune conditions, particularly auto-immune and inflammatory disorders.
The increase in auto-immune diseases — type 1 diabetes, arthritis, multiple sclerosis — over the last few decades in the Western world is now believed to be more related to low fibre and high fat than to cleanliness (which may still account for the increased incidence in allergies).
But the interconnectedness of our microbiota and us goes beyond these disease states. Bacteria and parasitic worms have also been known to modulate the immune system by secreting molecules that mimic hormones.
In releasing hormones, our gut microbes might be influencing us in unexpected ways, both physically and mentally. They influence our brain's development at infancy and cause biochemical changes in the brain that can and do affect our moods throughout life. It may well be that the way children's brains develop — their cognitive and emotional characteristics — is affected by the bacteria they have in their tummy — and in this case, a too-clean environment could mean a poorly stocked gut.
In a guest post in Moselio Schaechter's blog Small Things Considered, microbiologist Micah Manary goes so far as to speculate that perhaps the high modern incidence of cognitive disorders such as autism and ADHD 'may be causatively linked to the increased sterility of our environment, rather than to parenting styles or to as yet unknown neurotoxins'.
Already, a study on mice has shown that the composition of gut microbiota can affect risk-taking behaviour. Many psychiatrists would not appreciate microbiologists entering the mental-health arena, but there are doctors out there who, even now, are starting to take the gut-brain connection seriously and are prescribing treatments such as probiotics to people suffering from disorders like OCD.
Perhaps they'll soon be prescribing a walk in the bush as well.
The air that we breathe
We spend nearly all of our time inside enclosed spaces — at home, at work, on the train, in the car — and these places have different microbial ecologies than are found outside our walls.
We might think that indoors is a healthy, clean, well-regulated environment, but environmental microbiology is starting to tell us differently: that our bodies, which have been living outside since forever and have only quite recently bothered with this 'indoors' thing, might, in fact, need the exposure to the diverse microbial communities that are to be found outdoors, where there is no artificial ventilation and no wall-to-wall carpet, but there is a diverse collection of ecological niches and a dazzling selection of microbes.
Indoor air is, unsurprisingly, mostly composed of microbes we brought in; we're essentially wallowing in our own microflora. The air outside has a radically different microbial composition than the stuff inside. And it could well be that we need a regular dose of the microbes that are found on the ground and in the air, just to keep our own microbes from asserting their presence too much.
All this can now be studied through new mass environmental DNA sequencing techniques, so listen for announcements.
And with this, I conclude. Thank you very much for reading. Now let's all go outside and play.