The Mind, The Brain and Immunity

With a few quick google searches it is easy to find an assortment of dubious claims about mind over body healing. Energy channels, psychic healing and think-yourself-healthy self-help websites are a dime for every dozen duped, desperate or misinformed reader. However, discussions about the mind influencing the body’s functions, and the health of the body influencing the mind, have been a persistent part of folk medicine for centuries.  The question then soon arises, to what extent, if at all, is there a scientific basis to such claims, removed from all the woohoo of alternative medicine?

Taking up the challenge of answering this question is the burgeoning field of science known as psychoendoneuroimmunology. Now, I know the name’s a mouthful, but don’t be put off by this multisyllabic monstrosity! Some of the most interesting and beneficial ideas in science arise from collaborations between different and diverse fields of inquiry and it is this communication that the term is trying to capture. By breaking psychoendoneuroimmunology into its parts we can see psycho- (from psychology), endo- (from endocrinology – the study of hormones), neuro- (from neuroscience) and immunology (the study of the immune system). Putting these concepts back together we can state that this multidisciplinary field studies the interaction between psychological processes (our thoughts, emotions, behaviours and perceptions), the nervous system (our brain and its associated hardware), the endocrine system and the immune (defensive) system of the human body.

At the core of psychoendoneuroimmunology is the empirically based understanding that neither the nervous system nor the immune system exist in isolation. Rather, they both possess the ability to communicate with one another, either through direct connections or indirect signals sent via hormones. Consequently, each system has the ability to influence how the other functions within the body, both when it’s healthy and when it’s not. Moreover, this cross-talk between the nervous and immune system is not limited to the ticking over of “basic” biological and chemical processes. Instead, the communication extends far enough to influence how our brains – and the minds they produce – function, in such a way that nervous-immune interactions can influence how we perceive sensations, our emotions and even how we think and behave. [1]

In order to examine psychoendoneuroimmunology I have divided this post into two parts: First I’ll present the ways in which the brain is able to influence the function of the immune system – and thus the health of the body – during psychological stress. Then I turn to look at how the immune system can influence the brain’s activity during the course of an infection in order to demonstrate how the body can influence the mind.

Brain to Immune Communication

Two major pathways exist which allow for brain to immune communication: The sympathetic nervous system (SNS) which asserts its control via direct signals from the brain, and the hypothalamus-pituitary-adrenal (HPA) axis which involves indirect communication from the brain via hormone mediators. Both of these pathways are classically involved in the body’s stress response, poetically known as fight or flight. The SNS is made up of nerves extending out of the spinal cord which – along with stimulating adrenalin release, increasing heart rate, dilating the pupils and expanding the airway – connect to a number of immune specific organs in our bodies including the lymph nodes, spleen, thymus and several other important immune structures. The nerves of the SNS release the neurotransmitter (nerve signalling molecule) noradrenalin which can either act on these immune organs directly, or influence how immune cells function.

The HPA axis, on the 324567865467other hand, achieves its effect by releasing hormones from the brain which travel in the blood all the way to the adrenal gland, leading to the production of glucocorticoids, the most prominent of these being cortisol. Both noradrenalin and cortisol are known to have immunosuppressant effects, which is designed to alter the immune system’s response to inflammation. Such effects prove beneficial in the short term because during limited duration stress – like running away from a hungry-looking bear – the effect of these signals down-regulates some aspects of the immune system while up-regulating others.

Specifically, this effect preserves humoral immunity, which works against nasties found outside our body’s cells such as parasites and bacteria, while suppressing cellular immunity, which attacks viruses and the like, who make their home on the inside of our cells. [2] (This effect proves especially useful if the bear manages to take a bite out of you as humoral immunity is our first line of defense during wound healing). However, in states of chronic stress, which occurs when the fight or flight mechanism is active over a prolonged period of time, this effect is far less one-sided, resulting in disturbances to the body’s expected balance for normal immune function.

When Fight or Flight Becomes Chronic

Those of us experiencing stress in our daily lives, suffering from depression, or having relationship problems are at a greater risk for health issues. For example, individuals suffering from depression are at a greater risk of developing osteoporosis, coronary heart disease, suffering a heart attack or developing metabolic syndrome, all of which are diseases with immunological features. [3] This raises the question: Why are people who are suffering from psychological illnesses such as chronic stress or depression more likely to experience diseases of the body? Chronic psychological stress presents with a host of negative consequences, influencing all of our body’s major organ systems. Moreover, suffers of chronic stress often experience a range of comorbidities (illnesses which occur at the same time), including anxiety, depression and sleep disturbances. And to top it all off there are millions of sufferers all across the planet!

But hang on – I hear you ask – didn’t you just say that stress is useful for our survival? Well, yes, acute stress is an important part of our evolutionary survival kit, promoting beneficial immune responses when active for only a short period of time. But when our fight or flight response remains on “high alert” for days, months or even years (as opposed to minutes or seconds) serious problems start to occur.

When we experience a heightened sense of threat in our everyday life we produce continuously high levels of stress hormones via the SNS and the HPA axis. This in turn leads to a persistent excess of the specific class of immune signalling molecules known as pro-inflammatory cytokines. These cytokines act as the “go go go!” signal for immune cells and are important for getting our immune system into gear. However, this response is supposed to go away after an infection, tissue damage, or perceived threat has cleared. If it does not, these pro-inflammatory cytokines are able to wreak havoc, signalling to an angry immune army that is unable to find itself an enemy, turning instead on the body it was created to protect. And to make matters worse, chronic psychological stress often causes insomnia in its sufferers. Sleep is a psychological phenomenon that has important regulatory effects on the immune system, diminishing the signalling of the SNS and HPA axis. Chronic sleep disturbance therefore produces a plethora of negative consequences, including a reduced response to vaccines and an increased susceptibility to infectious disease. [4]  Thus, it’s now widely recognized within the medical community that the inflammation caused by chronic psychological stress plays an important role in a wide range of diseases including asthma, some forms of cancer, arthritis, diabetes, obesity, hypertension and Alzheimer’s disease. [5]

Chronic stress may not result from being chased by a bear, but it has just as serious consequences and it is a major focus of psychoneuroimmunology to illuminate and ameliorate the negative consequences of this dangerous interaction between the mind and body.

Immune to Brain Communication

For a long time, the scientific community believed the immune system was isolated from, and had no way of penetrating into, the brain and spinal cord, which constitute what is known as the central nervous system (CNS). The main reason for this belief was that the electrochemical environment of the brain needs to be kept in careful balance. As a result of this fine balance, evolution provided our ancestors with a protective “shield” wherever the brain and blood interact. This shield is known as the blood brain barrier and as the alliterative name suggests acts as a highly selective gateway between the nervous tissue of the CNS and the contents of the blood vessels. However, in recent years this belief has changed drastically as more and more evidence comes in as to just how porous this barrier is.

This porosity of the blood brain barrier is most pronounced in the ventricles of the brain (large fluid filled cavities), allowing the cells and cytokines of the immune system to pass into the brain. Numerous studies have now shown that immune cells – and the cytokines they produce – are able to transverse the blood brain barrier, influencing the function of both neurons (signalling cells of the CNS) and glial cells (the “support and maintenance” cells of the CNS). [6-7]

An even more recent discovery in 2015, by Louveau and colleagues [8], found lymph vessels intimate to the meninges, which are the brain’s protective coverings. Lymph vessels are tube-like structures (similar to arteries and veins) which carry a substance called lymph and they act as a major transport highway for the immune system’s wandering cells. As a result, this study was the first to show a direct mode of communication from the immune system into the brain. This is a landmark finding in the field, inviting a new route to investigate the cause of neurological disorders associated with immune dysregulation including Alzheimer’s disease, depression and multiple sclerosis.

From Sickness unto Health: The Psychoneuroimmunology of the Sickness Response

Our immune cells, which we now know wander into and influence the CNS, also produce a response which I’m sure you’ve all experienced.

You have a cold and you feel awful. And it is not just the runny nose, sore throat and cough. You are also grumpy, can’t eat and you’re tired. Why the heck do you feel so miserable? Well, you can thank your immune system. Or, more specifically, you can thank the set of behavioral and affective (experiential) changes brought about by your immune system in response to the invasion of your body by bacteria, the flu or any other pathogen that wants to make your body its reproductive playground. 

The phenomenon to which I am referring is called the sickness response and it is 345345346534645characterized by a set of psychological changes which include tiredness, anxiety, mood instability, loss of appetite, feeling weak, an inability to concentrate, restricted memory formation and an increased sensitivity to pain. Now, you may think that it’s the bad guys in your blood stream causing all this havoc, but in fact all of these behavioural and experiential changes are brought about by the immune system, which has been activated by the breakdown products of the infection. Once these breakdown signals are in the blood your immune cells/cytokines makes their way into the CNS, activating, among other cells, microglia, which act as the on/off switch for the sickness response by altering the activity and sensitivity of particular neurons. [9] This in turn alters how we behave. Such behavioural changes prove to be evolutionarily adaptive as they induce actions which cause you to retreat from activity and remain stationary during the period of illness. This in turn allows your body to concentrate on the job of getting rid of the infection.

Final Thoughts

As you can perhaps guess from the diseases listed throughout this post, the story of psychoendoneuroimmunology is both promising and complex. The account sketched above is just the basics and we certainly don’t yet understand the nature of all the psychological-brain-immune connections and how they result in such a variety of effects. Although psychoendoneuroimmunology is making positive strides towards developing an integrated understanding of treatment methods, there is still a long way to go. In addition, it’s likely that even more factors, such as genetics, will have to be integrated into this framework before we have the full picture. (Who knows, perhaps we’ll soon have a blog post on psychoendoneuroimmunogenetics!). But that’s enough abuse of the English language for one day. I hope you have enjoyed this whirlwind tour of psychoendoneuroimmunology and are now as excited as I am to follow the progress of this novel way of investigating the how the mind, brain and body interact.

References

1. Pariante, C., Psychoneuroimmunology or Immunopsychiatry? The Lancet Psychiatry, 2015, 2(3), p. 197–199.

2. Segerstrom, S., Miller, G,. Psychological Stress and the Human Immune System: A Meta-Analytic Study of 30 Years of Inquiry, Psychol Bull. 2004. 130(4), p. 601–630.

3. Jaremka L, Lindgren, M, Kiecolt-Glaser, J., Synergistic relationships among stress, depression, and troubled relationships: insights from psychoneuroimmunology. Depress Anxiety. 2013. 30(4). P. 288-96.

4. Irwin, M,. Why Sleep Is Important for Health: A Psychoneuroimmunology Perspective. Annu Rev Psychol. 2015. 66. P. 143-725.

5. Couzin-Frankel, J., Inflammation bares a dark side,. Science, 2010. 330: p. 1621.

6. Ransohoff, R, Engelhardt, B,. The anatomical and cellular basis of immune surveillance in the central nervous system. Nat Rev Immunol. 2012. 12(9), p. 623-35

7. Ransohoff, R, Kivisäkk, P, Kidd, G,. Three or more routes for leukocyte migration into the central nervous system. Nat Rev Immunol. 2003. 3(7) p. 569-81.

8. Louveau, A, et al,. Structural and functional features of central nervous system lymphatic vessels. Nature. 2015. 523(7560). P. 337-41

9.  Konsman J, Parnet, P, Dantze R., Cytokine-induced sickness behaviour: mechanisms and implications. 2002. Trends in Neuroscience 25(3) P. 154–159

Image Credits

                                                  Lady in Bed: Painting by József Rippl-Rónai                               

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