Lifestyle & Longevity: Building Immune System Competence
“How do we feasibly adapt our lifestyle approaches to strengthen our immune system?”
The immune system is critical for our overall health outcomes and well-being over a lifetime. It is integrated into all aspects of our physiology and operates to protect us from both infectious disease and non-communicable chronic illness. The idea of ‘boosting’ one’s immune system, therefore, presents an appealing focus for many to help maintain and improve health. In this article, we cover research-based strategies on how to give our immune system the upper hand.
“As a consequence, there is no magic bullet or single solution available to bolster our immunity”
Our immune function has evolved as a finely balanced and complex macrocosm of organs, circulating cells, proteins and regulatory molecules that protect us from all manner of invading pathogenic microbes, toxins and allergens. As a consequence, there is no magic bullet or single solution available to bolster our immunity. How do we then feasibly adapt our lifestyle to support it?
In the first instance, it’s important to recognise that the immune system operates through two complimentary functions, or responses, referred to as innate and adaptive immunity.
Innate immunity includes physical barriers such as the epithelial cells that cover and line the surfaces of our bodies, the mucus that overlays them, and the microscopic hairs known as cilia that move to refresh the mucus and remove anything foreign that may have been inhaled or ingested.
Innate immunity is also provided by our white blood cells or leukocytes. Examples include dendritic cells, macrophages, mast cells and neutrophils — all with unique functions.
There are receptors on the surface of leukocytes that help produce a rapid non-specific immune response. They bind molecular patterns that are commonly expressed on a large number of foreign pathogens or toxins, and are not present in our own body [Chaplin DD. 2010]. This recognition of “non-self” is very important for an appropriate immune response. In addition, these cell types produce signalling molecules like cytokines, that cause inflammation and further increase white blood cell migration to a site of infection.
Other elements of innate immunity are circulating plasma proteins, known as the complement system. They bind to the surface of pathogens directly and mark them out for destruction.
The innate immune response is a rapid, first line of defence against an immune threat and is known to last between 4-7 days, before the synergistic adaptive immune response kicks in. [Janeway CA. 2001]
Adaptive immune function is mediated by cells called lymphocytes, predominantly two types known as T-cells and B-cells. These cells are produced and activated by signals from the innate immune system. T-cells have different roles, including killing their target cells, or regulating the immune response. B-cells are most commonly known for their function as antibody producing cells, although they have other essential roles in the immune system [Chaplin DD. 2010].
One of the outcomes of an adaptive immune response is the creation of memory T-cells and B-cells. The other cells that have been involved in an immune reaction are cleared from the system. Memory cells carry an immunological recall and respond rapidly in the future if we suffer a repeat infection from the same pathogen. Adaptive immunity therefore is distinguished in having a memory [Chaplin DD. 2010].
Every stage of our immune response can be affected by a number of lifestyle factors. We discuss the impact of these individually, and approaches for optimisation in the rest of this article.
“Every stage of our immune response can be affected by a number of lifestyle factors”
The role of micronutrients for optimal immune function
We often hear reference to a study in the media of a particular mineral or vitamin being critical to the immune system, which may increase our propensity to reach for a supplement as a universal fix when we feel we’re succumbing to illness. However, the role of micronutrients is a varied and complex one. Indeed, there are numerous studies to show that vitamins A, C, D, E, B2, B6, B12, folic acid, and the minerals iron, copper, selenium, magnesium and zinc have all been found to be essential for immunocompetence [Maggini S. et al., 2018; Gombart AF. et al., 2020]. There is particularly strong evidence for an immune support function for vitamins C and D and zinc, which we will explore below. However, it’s important to note these act synergistically with multiple other micronutrients at every stage of the immune response.
Vitamin C is not, as sometimes purported, a one shot fix to all things immune, but undoubtedly has some central roles in immune function. These include, but are not limited to, acting as an antioxidant against damaging reactive oxygen and nitrite species produced when pathogens are killed, stimulating the production and movement of leukocytes, supporting the integrity of epithelial barriers, and key roles in the proliferation of lymphocytes and antibody production [Carr AC and Maggini S. 2017; Jacob RA. 2002].
Vitamin C RDA’s for adults are commonly 75mg for women and 90 mg for men [Institute for medicine US. 2000]. Although some suggest saturating plasma levels of vitamin C (100-200 mg) can be used prophylactically to reduce the risk of infection [Carr AC and Maggini S. 2017; Balz Frei et al., 2012 ]. Other peer-review suggests this may shorten the duration of infection, rather than preventing us catching it [Hemilä, H. 2013]. It’s important to note that at high doses, >1g per day, most of it will be excreted in our urine.
Vitamin D is known to have a key role in the regulation of immune function, with most immune cells possessing receptors for it. Some of its actions are an ability to promote differentiation and movement of the many white blood cells in the innate immune response, and inhibit aspects of adaptive immunity. It has also been identified as regulating antimicrobial proteins, that can help the gut in immune defence and protect the lungs from infection [Gombart, A.F. 2009].
Zinc helps maintain the integrity of skin and mucosal membranes. In addition, it has been shown to have a critical role in the function and survival of leukocytes of the innate immune system, T- cell proliferation and differentiation, the complement protein pathway and also antibody production. A decline in the functioning of the thymus (thymic atrophy) – a central organ to healthy immune function, is also seen in zinc deficiency [Gombart AF. 2020].
There is evidence to show that as we age, supplementation of key micronutrients may be beneficial as poor absorption reduces their bioavailability from a standard balanced diet [Maggini S. 2018]. This may be compounded by a less varied diet in some older individuals. So even though our overall required calorie intake reduces as we get older, our relative micronutrient requirements may increase.
In addition, individuals who smoke, have high levels of stress, or are subjected to high levels of pollution require higher micronutrient dietary intake, to counteract the deleterious effects of these factors on their stores [Gombart AF. 2020].
Our gut microbiome has a crucial role
As well as the pathogenic community of microbes we encounter during our lifetimes, many other beneficial ones exist, which use our body as a host in a commensal and mutualistic manner. They help support our normal tissue and organ functions in turn.
There are several such varieties of microbes including bacteria, archaea, yeast, fungi and viruses. Much of the viral count is made up from bacteriophages – viruses that infect bacteria. In totality, some estimates suggest that the human gut may be populated with as many as 100 trillion microbes, the majority of which are located in the colon, and whose collective genome is referred to as the microbiome.
Some microbes are ‘entrenched’ in that they are permanently housed on the gut wall, others are ingested. In addition to dietary roles like helping digestion, synthesising beneficial micronutrients and metabolising others in a useful way, our gut microbiome has been found to have a critical role in immunity.
The gut forms a central point of congregation for many immune cells. They work alongside an epithelial cell and mucus layer in an effort to produce an effective barrier against the microbiome, which is sometimes known as the ‘mucosal firewall,’ thus preventing an unintended immune response against beneficial microbes. The immune cell interactions and signalling responses here are thought to have several beneficial effects to our body’s immunity at large, such as by producing antimicrobial proteins and molecules that adversely affect the survival and virulence of pathogens.
As a result of the research into the role of our microbiome in immune system competence, it is increasingly recognised that fostering a healthy, diverse universe of microbes in our gut contributes substantially to our overall health and ability to fight disease. Not surprisingly, this also comes back to having a balanced diet of the kind referenced above. More specifically, pre-biotics – that help feed the microbiota in our gut, probiotics that include ‘live’ commensal bacteria like lactobacilli and bifidobacteria, and fermented foods have all come into favour in recent years to support microbes and maintain diversity. We will cover the gut microbiome in greater detail in our next paper, dedicated solely to this topic.
Ensure regular, high-quality sleep
The optimal sleep level according to recent research is between 7-8 hrs per night for adults [Daza EJ et al., 2019; Chaput J,P et al., 2018]. Sleep and the body’s circadian rhythm show an intrinsic link to immunity. Fluctuations are seen in the number of circulating immune cells, molecules and overall function of the immune system, during different stages of the sleep/wake cycle.
Specifically, sleep restriction has been shown to perturb immune function. In one study even a mild reduction in the amount of sleep, from 8 to 6 hrs a night for a period of 8 days, was shown to increase pro-inflammatory cytokines. Sustained levels of these pro-inflammatory markers are associated with a wide variety of medical illnesses, including type 2 diabetes and cardiovascular disease. In a separate study, sleep deprivation demonstrated an increased susceptibility to viruses like the common cold [Besedovsky, L. et al., 2012 Review].
The adaptive immune response, and associated immunological memory is thought to be initiated during sleep. For example, studies looking at the response to a Hepatitis A vaccination showed that sleep bolstered the reaction two-fold. Sleep restriction, on the other hand, reduced the response against vaccination to the influenza virus. Studies have also shown that some types of T-cells migrate to the lymph nodes during sleep, which may support the adaptive immune response. Conversely, immune cells of the innate immune system that have more immediate actions, are shown to peak during wakefulness [Besedovsky, L. et al., 2012. Review].
In summary, many research studies highlight that getting a good night’s sleep is essential for optimal immune function. Inversely, sleep restriction, or deprivation acts as a stressor to disrupt immunity, with the potential to act as a contributory factor in the development of chronic illness.
“chronic stress starts to suppress the adaptive and innate immune response by decreasing immune cell numbers and function”
Use techniques to minimise and manage stress
The major mediators of stress in our bodies are the neuroendocrine hormones adrenaline, noradrenaline, corticotropin-releasing factor (CRF), adrenocorticotropin hormone (ACTH), as well as the glucocorticoid — cortisol. Together these make up what’s known as the hypothalmic-pituitary-adrenal (HPA) axis — a feedback loop between the brain and adrenal gland that regulates stress. There are many pathways connecting the HPA axis and the immune system. For example, many white blood cells bind the hormone mediators of stress directly [Segerstrom SC. and Miller JE. 2004].
There are several studies examining the effects of stress on the immune system. A distinction is often drawn between short-term stress, of the ‘fight’ or ‘flight’ type — lasting minutes to hours, versus chronic or long-term stress. The latter being defined as lasting for several hours per day over weeks and months. Short-term stress can actually enhance the immune system to an extent, particularly the innate response, mobilising it against pathogens. In contrast, chronic stress starts to suppress the adaptive and innate immune response by decreasing immune cell numbers and function, in conjunction with an increase in inflammatory and autoimmune responses.
Using interventions designed to minimise the effects of long term stress in our daily lives, can therefore help maximally promote health and healing [Dharbar 2009, 2014].
Smoking is known to cause cancer and increase the risk of stroke and cardiovascular diseases. In terms of the immune system, research has shown that smoking alters the development, cytokine release, and function of both innate and adaptive immune cells, with a potential to lead to pro-inflammatory responses and dysfunction in immunity. Several studies have linked smoking to auto-immune diseases including rheumatoid arthritis, Crohn’s disease and ulcerative colitis, amongst other conditions highlighted in a recent review [Qiu, F. et al in 2017].
Another study has implicated exposure to cigarette smoke (including second-hand smoke) directly to graft rejection [Wan F., et al 2012]. Whilst further research is needed to elucidate the precise mechanisms responsible for the many smoking-mediated immune effects, it is clear it has damaging outcomes. Therefore, smoking cessation should be considered to be crucial to any efforts to improve immune function.
Reduce your exposure to air pollution
Ambient pollution levels have reached concerning levels globally, with the World Health Organisation (WHO) stating that 91% of the world’s population live in areas of pollution above accepted levels. According to their estimates, outdoor and indoor (household) pollution is thought to contribute to as many as 8 million deaths combined a year. For context, this figure is comparable to the annual number of smoking-related deaths worldwide.
Air pollutants, including particulate matter, mainly deposit themselves on the respiratory airways and the cells that line them, which has been a focus for much of the research in the area. The common effects seen are increases in pro-inflammatory immune responses across multiple classes of immune cells at this location. This has been linked to exacerbations in asthma, allergy and chronic obstructive pulmonary disease (COPD), as well as reduced anti-viral responses. [Glencross, D.A., et al 2020].
Furthermore, studies have also linked air pollution to more diverse immune system problems, including effects on immune development in the neonate, and alterations in the gut microbiome in adults [Glencross, DA. et al., 2020; Dujardin, C et al 2020]
Avoid excessive alcohol consumption
Alcohol consumption has been shown to be detrimental to immune function in a dose dependent manner. Whilst low to moderate alcohol consumption does not show any significant effect, heavier drinking is shown to disrupt innate and adaptive immunity through multiple pathways.
Elevated blood concentrations of ethanol have been shown to interfere directly with the ability of white blood cells to recognise and bind endotoxin, a toxin released when bacteria are destroyed and a key marker of bacterial pathogens, resulting in an increased susceptibility to disease. Heavier drinking reduces the number of dendritic cells, that are key to activating the adaptive immune system into antibody production and pathogen destruction. Other studies have shown a reduced T-lymphocyte population, faster progression rates of viral infection, poor outcomes following injury and deficient wound healing [Molina, PE et al 2010]. Some sources suggest the gut may also become more ‘leaky’ to pathogens after chronic alcohol exposure, resulting in pathogenic molecules crossing into the blood stream [Barr, T. et al., 2017; Sureshchandra, S. et al., 2019].
To be safe, moderate or low risk alcohol consumption should be in line with current government guidelines, which in the UK are a maximum of 14 alcohol units a week or less, for both men and women – equivalent to a maximum of 6 glasses of 175ml wine, 6 pints of beer, or 10 X 25ml shots over 7 days – with designated drink free days across that period. The guidelines in the US are comparable.
Go for moderate, or vigorous, regular exercise <60 mins duration
Exercise has been shown to modulate the immune system in a complex way, dependent on the intensity and duration of the physical exertion. Some documented effects of moderate- and vigorous-intensity aerobic exercise, of less than 60 minutes duration, show a bolstering of the innate immune response. This includes the improved anti-pathogenic activity of macrophages, enhanced circulation of neutrophils and an anti-inflammatory effect. This occurs in parallel with an improved circulation of adaptive immune elements such as cytotoxic T-cells, and immature B-cells, all of which play critical roles in immune defence activity. Metabolically, this sort of exercise can also improve glucose and lipid metabolism over time [Gleeson, M. 2015].
Conversely, immune responses to the type of prolonged and intensive exercise undertaken by professional athletes, have been shown to result in transient immune dysfunction lasting from hours to days [Gleeson, M. 2015] although the long term effects are still being disputed amongst researchers [Campbell, J. 2018].
Ultimately, a lack of exercise and sedentary lifestyle can lead to obesity, that is associated with immune dysfunction, and increased risk to infections [Milner, J. 2012]. Exercise has also been shown to help mitigate the effects of ageing on immune function [Campbell, J. 2018].
A note on immunotherapy
The clear link between lifestyle adaptations and immune system competence is encouraging. We really are in control of much of our health. Moreover, medical advances have shown that our immune system can be manipulated to further help prevent and fight disease. Vaccines are a primary example of this. Here a small amount of altered or inactivated pathogen is injected that can’t in itself cause disease. It effectively hijacks our immune response so that we produce antibodies to protect us against future infection. Catastrophic and fatal diseases like Small Pox have been eradicated as a result.
Recent advances go further. Cancer immunotherapy uses several approaches to harness the power of an individual’s own immune system to attack tumour cells. For example, in chimeric antigen receptor (CAR) T-cell therapy some of a patient’s own immune cells (T-cells) are collected from their blood and modified so they specifically attack cancer cells when introduced back into the body. At present this therapy has shown to be effective in some specific blood cancers (childhood lymphoblastic leukaemia, and lymphoma) [Almåsbak H, et al 2016, Review].
Other types of cancer immunotherapies include monoclonal antibodies that specifically attach to tumour cells, identifying them for destruction by our own immune system. Vaccines are also in development, where components of different types of cancer cells are being used to try and elicit an immune response. Other approaches include administering specific signalling molecules in the immune system called cytokines. One of their mechanisms of action includes encouraging our killer T-cells to attack tumour cells.
Immunotherapies for the treatment of all types of cancer are at a preliminary stage, with applications in a limited number of tumour types. However, research and clinical trials are emerging at a fast pace, and targeted immunotherapy, annexing our own immune system offers much promise for combatting cancer in the future.
“…we can conclude that healthy-living strategies of the kinds outlined, will give our immune systems the best chance of fighting infection and much chronic disease”
Here we highlight that building and maintaining optimal immunocompetence requires a multi-faceted approach. The immune system is infinitely complex, with researchers still trying to decipher many aspects of its function. It is clear that immune system dysfunction can be problematic and is intrinsically linked to adverse health, including susceptibility to infection, the development of auto-immune diseases and co-morbidities, some of which can significantly reduce lifespan.
Avoiding exposure, and minimising the risk of infection sources through hygiene is very relevant in today’s climate. Furthermore, identifying the specific causes of a weakened immune system – for example nutrient deficiencies – requires clinical tests to ensure appropriate actions are be taken.
There are several lifestyle factors that we can optimise to bolster our innate and adaptive immunity. Studies to date indicate the influential effects of diet, age-related supplementation, gut health, sleep, psychological stress, air pollution, alcohol, smoking and exercise on the immune response. Whilst further research will provide further clarity, we can conclude that healthy-living strategies of the kinds outlined, will give our immune systems the best chance of fighting infection and much chronic disease.
Dr. Seema Sharma for SX2 Ventures © 2020
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