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Fluid Intelligence: The Immune System, Part 2


The Waterfall

The year was 1910 and in Japan a young man called Tempu Nakamura was facing his own death. It was not the first time. As a spy working covertly for the Japanese military in Manchuria, he'd been shot, starved and miraculously saved from a Russian firing squad by his comrades. He'd dished out his share of death too - putting his samurai sword to use against marauding bandits for instance, and delivering bloody vengeance on Russian soldiers who had themselves murdered three Japanese geishas some days before. These were not gentle times. But on his return to Japan he faced a more insidious and intractable enemy: tuberculosis. At the time there was no cure for TB and a gloomy Nakamura - previously a fit martial artist - resigned himself to a premature, cough-racked death. Fate intervened however, in the form of an Indian sage called Kariappa who he met one day in a waiting room and who, in a somewhat cinematic turn of events, invited Nakamura to study with him in the mountains of Nepal. Racked by coughs and fatigue, Nakamura nevertheless made his way to the verdant foothills for a two year stay.

This was no luxury retreat. In the morning mist he would join a handful of other pupils and sit up to his chest in a freezing stream for an hour. After, under the sage's goading, he would hike up a mountain to a waterfall, next to which he would spend the rest of the day meditating. As the months passed Nakamura began to change. The morning dips in the icy mountain stream, once torture, began to feel calming and even pleasant. After many weeks spent meditating by the waterfall his mind began to clear. His coughs subsided, his fatigue lifted and his mood improved. After many months of this he realized that his symptoms had vanished and he had never felt so strong. The spectre of death had vanished.

Yet, without regular practice not even enlightenment lasts and, after bidding farewell to his mentor, Nakamura returned to Japan whereupon he promptly lapsed back into his bad old ways - namely smoking, gambling and idleness. Before long the malaise and the coughing crept back in. However this time he knew what was needed - he was 'mentally immunized' you might say - and he soon resumed his meditation and cold water soaks, became a committed pacifist, and eventually went on to develop a kind of 'Japanese yoga' system called shin shin toitso do (loosely translated as 'mind-body harmonization') which is still practiced to this day. His tuberculosis disappeared for good this time, and he went on to live a long and fruitful life.

Many aspects of Nakamura's story seem fantastical, though they are backed by the record. Yet, one has to ask: how valid is his tale of 'curing' himself of an incurable disease? Granted, tuberculosis does not kill everybody who gets it, but Nakamura certainly seemed to be one of the unlucky ones: before his trip to India he was losing weight rapidly, sweating profusely at night, and coughing up blood; all of which indicate that the 'bacterial load' of TB had overwhelmed his immune system and was destroying his lungs. However, in the days before antibiotics he was somehow able to reverse this process. He was able to boost his immune system enough that it would contain the infection and later it seems, effectively 'clear it' from his body.

The question is how? What 'mechanisms' might explain this recovery? What role does 'mental attitude' play in the recovery of the body? We tend to overlook this aspect, particularly in our 'biomedical' approach to medicine. We might not say so explicitly, but so much of modern medicine is based on the assumption that the mind does one thing and the body another. Sure, we know that mental attitudes play some role in physical well being. Positive, optimistic mind states are associated with better outcomes for many diseases. But the how remains somewhat vague. Is it chemical, hormonal, neurological? Where the mind and body interact is a kind of foggy no-man's-land.

This question is especially relevant question among the current coronavirus pandemic. Whatever your opinions on government policy are, ultimately one has to focus on the things one can control; and in our case, as well taking measures to reduce exposure to infection, it also includes attending to our own thought processes, attitudes and bodies. It might be instructional therefore to take a closer look at the relationship between the mind, the body and the immune system. What we find is that the immune system is actually not just 'in the body', but actually a kind of intelligence that connects body to mind.

Immunity and the Brain.

In normal conditions the brain is protected from the immune system by the blood-brain barrier (BBB). In cases of quite advanced infection - such as meningitis - this barrier is leaky enough that microorganisms can cross it, though normally it remains strictly closed off to such pathogens. In fact the BBB is even impenetrable to the body's regular immune cells and depends upon its own class of cells called microglia. These microglia are able to identify damaged or diseased nerve cells, using phagocytes (cell eaters) to limit any damage and clear up. Like any complex system the brain's immune system can become dysfunctional and is implicated in such conditions such as multiple sclerosis and Alzheimer's disease, and even depression.

[The immune-inflammatory response has been put forward as a mechanism by which vaccinations might lead to autism - the theory being that the immune-inflammatory response to the vaccine causes neuronal damage. However, and this point needs to be stressed, there is no established link connecting the two, and I would encourage the reader to look at the Immunization Safety Review: Vaccines and Autism (2004) (available on www.nationalacademies.org) for reassurance on this matter.]

On a lighter note a more common manifestation of inflammation affecting the brain is the good old hangover – though actually that gnawing pain is caused by inflammation of the meninges (which cover the brain in a protective, nutrient delivering sheath) rather than the brain itself.

Inflammation, while necessary in the short term for clearing infection, repair and healing, is in the long term damaging: It impairs the functioning of the various cells, organs and systems of the body. It can cause microscopic scarring to tissue and damage to cells. We now also know that inflammatory molecules known as cytokines can cross the BBB, and therefore affect the central nervous system. The brain also produces cytokines in response to any kind of 'insult' - infections, trauma, stress, toxins and so on. In this way the immune system directly influences our behavior - making us feel fatigued, anti-social etc. - in other words 'sickness behaviors'.

So, we can see how the immune-inflammatory system affects 'us' - that is the mind, our moods and thoughts. This leads us to the question of whether our state of mind can influence it. In other words, can we consciously control or boost our immune system?

Holiday Cold

To approach this question we can look at a more familiar one: Why do I get a cold when I go on holiday? Most of us have an experience of this. We’ve been working hard, looking forward to a break but when it finally comes it is sullied by a runny nose, sore throat and other flu-like symptoms. How come? One explanation brings us back to our hypothalamic-pituitary axis (HPA). You’ll recall that when the immune system kicks into action the hypothalamus in the brain tells the pituitary gland to stimulate the adrenals above the kidneys into producing cortisol. Cortisol is a powerful anti-inflammatory and limits collateral damage from the inflammatory cascade.

Psychological stress also activates the HPA. This makes sense from an evolutionary perspective: there will be times when we can’t necessarily be laid up in bed recovering, sometimes we will need to ‘power through’ and in such circumstances the body will tip towards an ‘anti-inflammatory’ state. The cortisol will raise blood sugar, increase metabolism and dampen down pain. Accordingly, once the 'stressor' is removed – e.g. work, escaping a hostile tribe – and the 'holiday' commences there is a rebound effect whereby the HPA winds down, the cortisol dries up and that inflammation which was being kept in check now runs riot; hence the ‘fluey’ symptoms.

The immune system is directed by the brain in other ways. The autonomic nervous system responds directly to stress. You will have heard of the ‘fight-flight-freeze’ response initiated by the sympathetic system and the ‘rest and digest’ counter-response of the parasympathetic system. These systems use chemicals such as adrenaline and acetylcholine to speed up and slow down the heart, for instance. What is perhaps less well known is that the autonomic nervous system also directly innervates the immune system sending nerves to, for instance, the thymus gland, the gut, mucous membranes, bone marrow and blood vessels.

We now begin to see how our mental state can directly affect our immune system, especially 'psycho-social' stress (I prefer this term because most psychological stress is essentially social in origin). Broadly speaking, stress inhibits our immune response. Sometimes this is necessary but in the long term it impairs our ability to fight infection (or even malignant cells). Moreover chronic over-stimulation disorientates the feedback loops of the immune response. This imbalance can result in distressing and otherwise unexplained symptoms such as inflamed sinuses or gut pain, or 'psychosomatic' sickness behaviors’ like fatigue, depression or social avoidance, which can happen in the absence of any obvious pathogen.

The 'Loop Hypothesis'

The 'loop hypothesis' is a model which aims to explain why, in certain circumstances, we experience disease - sometimes in the absence of an identifiable cause - and what we can do to correct this. It goes something like this: Most systems in the human body operate through feedback loops, and it is disruption of these loops which can lead to chronic problems. We can, however, re-train ourselves so that these loops can be restored to optimal functioning, and therefore return the organism (i.e. us) to a state of well-being.

An example of this is the immune response*. As we saw in Part 1, the immune system works through a series of feedback loops. A pathogen gets into our body and starts to multiply. The innate immune system kick-starts into action to combat the infection. If we're lucky we will also have anti-bodies to this infection which will be latching on to the bacteria or virally-infected cells and marking them for destruction, so that they can be cleared before they reach a significant number. However the immune system will also be releasing chemicals to slow itself down (including the anti-inflammatory steroid cortisol) so that it does not cause too much damage. As the infection is cleared, these 'calming' signals increase until the system returns to a state of rest. The autonomic nervous system - with nerves running directly to immune tissue - is also coordinating the immune response.

Ideally this system works in concert to manage the process of 'infection/injury-response-recovery-switch off'. However because this same system is integrated by our nervous system, that same nervous system can cause problems. Stress is one key example. If we are perceiving - or predicting - a continual threat then the immune loop is being prevented from closing. Our minds are triggering a 'continual response'!

Take a Dip...

Can we train the immune-inflammatory system so that it is able to function as intended? In a word, yes. Let's return to the story of Nakamura. Every morning he would sit in cold water. Eventually he came to enjoy these sessions and was convinced they helped him overcome TB. Several studies now demonstrate an immunological benefit to cold water immersion (CWI) with one study in the Netherlands showing that participants randomly assigned to cold water showers (of no more than 90 seconds!) suffered less from cold-symptoms and were less likely to take time off work due to illness. Other research demonstrates that cold water exposure increases the quantity of certain immune cells.

How exposure to cold water enhances the immune system is still a matter of some speculation. We know that having a brief plunge into a cold pool or shower significantly effects the blood flow to the skin (hence the pink glow) and we know that our blood vessels are lined with immune cells so it's possible that cold water mobilizes the immune system in this manner. Another mechanism is that cold water immersion is an acute stressful event: It places the body (and mind) under a state of brief, quite intense, stress. However, and here is the key, the stress is only for a few minutes and is also under controlled conditions. It is then removed: One retires to a warm place, gets wrapped up and enjoys a hot drink. The 'burst' of stress is much more intense than chronic, insidious stress, but precisely because of this it is able to trigger the immune system into winding down. In such a way the stress response can be trained into responding to stress in a healthy way. [It should go without saying that if you're new to cold water proceed with caution. Never force yourself.]

...Break a Sweat...

It is now well established that physical activity has profound immune-boosting and anti-inflammatory effects. Also, as with cold water, exercise is a controlled burst of acute, voluntary stress which mobilizes the body and mind. Specifically, the sympathetic nervous system kick starts into action; blood is pumped to muscles, airways expand, and an array of chemicals are released (for example the cytokine IL-6 from contracting skeletal muscle, which is pro-inflammatory but which in turn activates the anti-inflammatory IL-10 molecule in a classic feedback loop. The anti-inflammatory cortisol is also released during exercise as are adrenaline and noradrenaline.)... In many ways this mimics the stress of an acute infection, only here the exercise stops after a relatively short time, the feedback loops close and the body returns to homeostasis. Again, in such a way the feedback mechanisms are encouraged to function as nature intended.

Exercise is also important in recovery. 'Post-infection malaise' is a very common phenomenon whereby the infection is more or less gone, but we nevertheless feel exhausted and even depressed for weeks after. This can partly be explained by the fact that the immune system makes significant demands on the body's energy supplies. Another explanation comes from the 'central governor' theory which proposes that our nervous system has a kind of 'default network' which tells us how much energy we have to spare. In the case of an infection this 'governor' will tell us not to waste energy - which it doesn't do consciously of course (no voice in the head) but through making us feel tired, exhausted even. This stops us from squandering precious energy and helps us recover. However, as we have seen, sometime this governor does not quite return to normal after the 'insult' but rather stays on high alert. It becomes 'sensitized'. Sometimes this goes on for weeks, and sometime the fatigue becomes chronic, lasting years. Here again it is likely that brief controlled bursts of exertion would be effective in 'resetting' the default network to a higher threshold - in other words telling it that the body is capable of far more than it currently 'feels' it is.

A final note on physical activity is that is mechanically helps the immune system. Immune cells such as CTL and TH cells patrol the blood vessels and the lymphatic system of the body, always on the prowl for potential invaders. One of the benefits of physical activity such as exercise, stretching massage or yoga, is that it helps the flow of the lymphatic system (which, unlike blood, does not have a pump of its own).

...And Relax

What about meditation? Research into this field has surged in the past decade, and although not conclusive, the findings so far are promising. A recent review of around 20 randomized controlled trials found reproducible evidence that meditation reduces inflammatory markers, increases CD4 (regulatory t-cell) activity and also increased telomerase activity (which has a protective effect on cells during division and thus reduces 'biological aging'). In any case regular meditation practice reduces psychological stress and allows the body to return to a state of rest, or 'optimal functioning' whereby the feedback loops are allowed to complete their processes unhindered by mental impulses. With practice, it can allow one to drop into the 'physical experience' of the body in a way maybe not experienced for many years, a state where, in the words of Zen master Shunryu Suzuki, 'the mind pervades the body'.

Good Fat, Bad Fat and Anti-Fat

Finally, what about diet? There is a lot of literature on this topic and it is a challenge to sift through the often conflicting evidence. What foods are inflammatory or anti-inflammatory? The evidence is mixed. Still, one thing we can say with confidence is that eating a large amount of food in one go does produce an inflammatory response from the body, so binge-eating is not a good long term plan.

Another proven fact is that adipose tissue (especially visceral fat, that is, fat around the internal organs) is pro-inflammatory. Fat cells release inflammatory molecules, known as adipokines, as well as hormones such as oestrogen. Fat is not entirely bad. In healthy 'just enough' adipose tissue there is an abundance of anti-inflammatory immune cells such as M2 macrophages and CD4 T-regulatory cells. However in the absence of physical activity and too many calories this adipose tissue switches to 'bad', pro-inflammatory fat (wherein M1 macrophages and activated T cells predominate and adipokines are released) leading to a state of constant, low-grade systemic inflammation. Therefore keeping physically active, even if one is a little overweight, is definitely a good long term plan. (Moreover muscle releases its own anti-inflammatory molecules called myokines, in this respect making it a kind of 'anti-fat').

Our Bacterial Garden

It is worth here making the point that normally our body is also stocked with various other micro-organisms and that many of these foreigners play an important role in our health - the billions of bacteria in our colon for instance which metabolize vitamin B12 for us - and their presence plays an important role in regulating our immunity. It's no coincidence that around 75% of the weight of the gut is composed of immune tissue. So what we eat is important, and foods rich in bacteria - probiotic yoghurts, fermented foods, raw food - probably introduce a lot of beneficial bacteria to our immune system. You could compare it to a garden; the more benign bacteria you have covering it, the less chance toxic bacteria have to flourish.

Stacking the Odds

One of the lessons from the current SARS-CoV-2 pandemic is that sometimes there is no immediate cure, no pill, no injection. This being a virus, we know that antibiotics are only useful in treating secondary bacterial infections. A vaccination is likely to be crucial in preventing further spread, but this is going to be many months away. It is a daunting prospect but not insurmountable. Ultimately it comes down to 'improving our chances' and this involves two approaches: reducing exposure to the virus and optimizing our immune systems so that we are more likely to be in that group of people whose symptoms are 'mild or minimal'. Some of that is outside of our control (the amount of certain receptors on one's cells for instance), but far more is and, as with so much, the body is the mind's greatest ally. Because while the body needs the mind to focus and direct it, the body is also so much older and wiser than 'us', and if we are able to work with it and harness its inbuilt capacity, it is capable of astonishing feats of recovery. To finish on the words of Nakamura 'since the body can only exist in the present that's where the mind should be too'.

- H James, May 2020

*This hypothesis can be used to explain other forms of dis-ease. Mental trauma is a familiar one. The traumatic event (say, an assault, or a partner breaking off a relationship) causes a disruption in our normal mental and emotional processes, causing a 'break' in the loop. Our idea of how things 'should be' is violently interrupted and there is an overwhelming feeling of 'unfinished business'. Our minds then become involved with trying to close this loop - obsessively re-living the events in the form of vivid flashbacks for instance, or intrusive ruminative thoughts. Unfortunately, rather than 'closing the loop', this mental activity only serves to reinforce its own behavior and if uncontrolled these thought eventually become new attitudes and behaviors. Talking therapies are one way in which these 'broken loop' can be closed.

Sources:

- Heaven's Wind: The Life and Teachings of Nakamura Tempu - a Mind-Body Integration Pioneer, Steven Earle (2017)

- 'Multimorbidity' as the manifestation of network disturbances, Sturmberg J.P, et al, Journal of Evaluation in Clinical Practice, 23, (2016) - 'The key pathways to health result from the modulation of the neuroendocrine and autonomous nervous system regulatory feedback loops. Chronic overstimulation of these pathways is the main contribution to poor health...'

- The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease, Gleeson M et al, Nature Reviews: Immunology, (2011)

- The effect of cold showering on health and work: A randomized control trial, Geert A.B et al, PLOS (2016)

- Mindfulness meditation and the immune system: a systematic review of randomized controlled trials, Black, D.S, Slavich G.M, Annals of the New York Academy of Sciences, (2016)

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About The Writer

HC James is from London and worked as a teacher before switching careers to medicine. He currently works as a doctor in a south London Emergency Department and in his spare time visits family in California.   

 

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