Building Immunological Strength: Immunity, Immunoscience & COVID19

Thursday, 26 March 2020

Not the most catchy of titles - sorry! I started writing this blog 3 days ago, and it’s just got longer and longer due to the many possible contributing factors that are at play in relation to the disease COVID19. I wanted to share measured and science based information with you, and I’ve had my head in the literature and mind-mapping the contributing factors to now share with you. I’ve written it in a way to answer the questions that have arisen in my mind, such as “why does it impact the over 60’s, or those with pre-existing health conditions more”, and used valid research to help me map this out for you. However, I must emphasise I am not a virologist, I am a health professional with a passion for science and helping you, my community in any way I can.

Firstly, let’s review the immune system, which is highly coordinated and complex. But if it becomes overwhelmed, a feed-forward cycle of excessive inflammation, tissue damage, low antioxidant reserves and the result is a diminished immune response and thus vulnerability can occur.   

The immune system is one of our most vital surveillance systems protecting us from outside pathogen like “invaders” such viruses and bacteria, we term these PAMPS (pathogen associated molecular patterns)  and “internal” damage molecules that are released from damaged or dying cells, termed DAMPS (Damage-associated molecular patterns). 

As I’ve written about previously the immune system is a collection of different specialised cells and tissues that  can be likened to the armed forces or military in the way it has multiple levels of intervention, attack and a more targeted stealth and SAS like attack. This diagram shows the basic types of cells, and how they are divided into the Innate and Adaptive immune response.  

Cells of the innate immune system are predominately the subset of your artillery that start the fight. One important group of cells are Natural Killer (NK) cells. NK cells are best known for killing viruses (like SARS-CoV-2) infected cells, and detecting and controlling early signs of cancer. NK cells have a unique ability to kill cells without any priming or prior activation (in contrast to cytotoxic T cells, which need previous exposure and memory priming). NK cells secrete cytokines (think about cytokines as messengers) such as IFNγ and TNFα, which act on other immune cells like Macrophages (more on them in a minute) to enhance and amplify the immune response.

While on patrol, whether or not the NK cell kills cells depends on a balance of signals from activating receptors and inhibitory receptors on the NK cell surface.

Normal healthy cells express little markers on their cell membrane (called MHC class I molecules for those that like the science) which act in an inhibitory fashion and contribute to self-tolerance and a quiescent immune state. However, a cell that becomes virus-infected cells (or tumor cells) lose this MHC class I expression, leading to a lower inhibitory signal in Natural Killer cells. Simultaneously, cellular stress associated with viral infection or tumor development such as DNA damage and changing the shape of the cell results in the release of that cell fragments and DNA which are DAMPS -  damage associated molecular patterns and drives activating receptors in these cells and the production of what we call co-stimulatory signals - cytokines. The result of both of these components, the signal from activating receptors in NK cell plus co-stimulatory molecules shifts the balance toward NK cell activation - seek, destroy and eliminate! Inflammation has started. 

Two other innate immune cells, neutrophils and macrophages (I told you I was coming onto these) are involved too. Following inhalation of a viral or bacterial infection the cells that are most vulnerable are epithelial cells - these are the cells that come from surfaces of your body, such as your skin, blood vessels, lungs, urinary tract and gut. They serve as a barrier between the inside and outside of your body. On “infection” these cells rapidly  produce cytokines and chemokines (basically think of these as the war cabinet sending the instruction “go go go … attack attack attack” to the military) and we see the subsequent recruitment of inflammatory cells, including neutrophils macrophages and finally T and B Lymphocytes which are the adaptive immune system and creating a memory. Neutrophils dominate the early stages of infection, they detect an intruder, squeeze out of the blood vessel and effectively tunnel towards their target taking it out either by engulfing it like Pac-Man, releasing more proinflammatory cytokines (remember the amplifying chemicals, Il1, Il6 and TNFa) or spraying it with deadly chemicals. The amplifying chemicals recruit other cells called macrophages that help to clear the “infection” and eventually T and B lymphocytes. The problem becomes, when there is too much of a cytokine storm and excessive inflammatory cascade to the point that the macrophages and resolution mechanisms become overwhelmed and then we become more vulnerable to autoimmunity and susceptible to COVID19 disease.

The takeaway:  effective resolution and memory are needed.

Reasons we believe SARS-CoV-2  is such an issue:

  1. Is to do with how SARS-CoV-2 virus has a unique ability to bind to a cell. With this particular virus there is a stronger cleavage site in the receptor meaning  more of the virus can infiltrate into the cell. 

  2. The virus that causes Covid-19 can latch onto a receptor called ACE2 undetected and gain entry to the cell. ACE2 receptors play a role in constricting blood vessels, and raising blood pressure and individuals with diabetes or high blood pressure - who are typically older adults - often take a class of drugs called ACE inhibitors. These drugs limit the constriction of blood vessels and, in doing so, make ACE2 receptors more prevalent - the theory then is allowing more of the virus into the cell and overwhelm the system. The ACE2 receptor is found abundantly on cells along the oesophagus, kidneys and heart, and our gastrointestinal tract—which is why symptoms, like loss of appetite and diarrhea have been observed. ACE2 receptors appear on cells in the most delicate part of the lungs: the alveoli. Damage to these cells is what causes some of the most common symptoms of the virus, like shortness of breath.

  3. SARS-CoV-2 virus contains certain virulence factors that stimulates a very strong immune response, and activates a super charged  inflammatory response in the form of creating inflammasomes - which creates a cytokine storm of over abundance and so resolution mechanisms become unbalanced. 

Vitamin D and A do not increase Ace2 receptors in any way as much as pharmaceuticals. 

So what has ageing got to do with it? 

Immunosenescence refers to the gradual deterioration of the immune system brought on by ageing. Immunosenescence involves both the host's capacity to respond to infections and the development of long-term immune memory - which is vital for remembering the virus a second time round, or even elements of the virus, even if it’s mutated. 

If we remember back to those neutrophils, the process by which neutrophils “tunnel” through tissues is called chemotaxis, and this becomes increasingly depleted and their efficacy is rather hit and miss as we age. The confused and “hit and miss” neutrophils cause significant cellular damage and this is problematic for two reasons:

  1. It reduces the speed and efficiency of the defence mechanism.
  2. It also causes more inflammation in it’s own right and there isn’t enough macrophages to come in to clear up the debris that the neutrophils are causing.

The other components to this is the adaptive immune system, which basically develops your memory T and B cells. These are produced in thymus and bone marrow respectively and sadly production slows with age, by about 3 per cent a year from the onset of puberty! 

This is where diet and lifestyle really comes into play. Reducing calorie dense nutrient poor foods is key. 

The key is to deactivate a calorie-sensing pathway inside cells called mTOR. When the calorie load is low, mTOR switches off and it’s this action that has been shown to improve immunosenescence!! So powerful is this mechanism, switching off mTOR, that drugs called mTOR inhibitors, the best-known being rapamycin are being used as “immune boosters”. 

For us, there are other ways to achieve mTOR inhibition through “fasting”. There are three main categories of fasting: time restricted fasting; intermittent fasting; and short term and prolonged or periodic fasting. Intermittent fasting, a temporary state of caloric restriction that is enough to switch off mTOR for a short while and still obtain its benefits. There are various regimes including the 16:8 diet, which involves completely eschewing calories for 16 hours and only eating in an 8-hour window. Even done once a week, this is an effective way of slowing ageing and strengthening the immune system. Finally, short term and prolonged, or periodic fasting, defines periods of consecutive days of fasting. Short-term (ST) is less than 3 days and Prolonged Fasting is 3 or more than days. This is the wonderful work of Professor Valter Longo and his Prolon Fasting Mimicking Diet, I wrote a blog on this here

Exercise is also a proven mTOR inhibitor and getting optimal sleep! 

What else can we offer?

I preempt this section by saying there is no cure for COVID19 to date, but we can help facilitate an optimal immune response by understanding mechanisms. 

  1. Facilitating Natural Killer cells into action with Astragalus, andrographis and reishi
  2. Improve innate (Th1) immune cell status which helps the neutrophil and macrophage response with berberine, sulforaphane (in broccoli sprout extract) and ginger
  3. Mitigate tissue damage and oxidative levels with glutathione and or NAC and vitamin C. Glutathione reduces lung inflammation while also supporting Th1 response, an essential component of competent immune response against viral burdens.
  4. Total avoidance of sugary foods and nutrient devoid high calories foods like pizza , pasta (which is sold out currently anyway!!) cakes, biscuits, crumpets etc
  5. Try to manage mental stress - which of course I know is so easy to say, especially right now! But stress chemistry (cortisol and Il6) drives inflammation. Try breathing techniques, yoga and being in nature.
  6. Melatonin which is a hormone produced in the brain stimulated by darkness and induces sleep is also shown to reduce chronic and acute inflammation. It acts on the immune system by regulating cytokine production of immunocompetent cells.
  7. Exercise - a study in 2016, measured exercise levels and neutrophil migration in 211 older adults. “Those doing 10,000 steps on average had neutrophils as good as young adults,” the study says.
  8. Taking small daily doses of vitamin E may help rejuvenate immune cells. 
  9. Vitamin D - A 2017 review of the evidence for taking vitamin D supplementation concluded that it prevents upper respiratory tract infections. About 1000 to 2000 IUs should be safe and beneficial
  10. Implement some form of time restricted fasting; intermittent fasting; and short term and prolonged or periodic fasting.

For any practitioners I will be delving more into immune cell differentiation and how to see this on a blood chemistry in my upcoming Virtual Masterclass on Interpreting Blood Chemistry on 21st April

For more information and resources for clients, think about my virtual day retreat: Taming Inflammation & Autoimmunity on the 29th April, especially if you have an autoimmune condition, as there is even more information I can share!  And of course I offer private 1:1 packages and appointments. 

In health as always, Tanya x