Immuno-Primers – How to Supercharge The Immune System
Victorian food contained far more yeast than today. It was clearly in bread and beer, but it also contaminated a large proportion of the other foods they ate. There are compounds in yeasts and fungi that naturally ‘prime’ your immune system to be in a high state of readiness to seek out and destroy invading pathogens. Unfortunately, these compounds, 1-3, 1-6 beta glucans, are now far less prevalent in our diets, due to food refinement techniques, over-processing and an excessive focus on kitchen hygiene.
T the spots on our apples – and indeed, the traces of yeast and moulds that used to be on almost all our foods – are now known to be as important for our health as the apples themselves. These micro organisms contain compounds in their cell walls known as 1-3, 1-6 beta glucans..
We now know that these compounds are critically important in priming a part of our immune system known as the innate immune system – but we no longer have many of them in our diet. It’s true that the Victorians ate a lot more fresh vegetables and fruits than we do now – and no highly processed foods at all. But they had another dietary element that allowed them to survive dangerous infections in a time before you could get engineered antibiotics.
That element was baker’s or brewer’s yeast.
Long before we evolved, all higher life forms were so surrounded by yeasts and fungi that our immune system evolved to combat the threat, so much so that it cannot work effectively without that stimulus!
All the medical research, spanning across two centuries has confirmed the fact that it is the Beta 1, 3d glucan linkage that ‘turns on’ the immune system.
The history of Beta 1,3-D glucan reaches into the middle of the last century. Dr. Louis Pillemer documented a material that was shown to produce amazing immune system support properties. It was given the name of Zymosan.
Later in the 20th century another doctor working at Tulane University identified the specific immune system support material as Beta-1, 3-D glucan. Medical studies on humans using this material started during the 1970’s and have continued up the the present day.
Immune function is further weakened by Type B malnutrition, a condition now recognized by the UN Standing Committee on Human Nutrition as a major cause of ill health. Type B mal-nutrition is characterized by a typical western diet – with sufficient – even excessive in calories – but often depleted in important vitamins, minerals and other nutrients.
The key to restoring optimum immune function is nutrition, and this involves not only good diet (one rich in fruits, vegetables and whole grains), but also a broad spectrum supplement, and a small number of key phyto-nutrients ie nutrients derived from plants.
1-3, 1-6 Beta Glucans – priming the immune system
Of all the natural compounds known to activate the innate immune system, the best documented and most effective are the 1-3, 1-6 beta glucans, generally derived from baker’s yeast. (Kernodle et al ’98, Wakshull et al ’99, Mansell et al ’75, Hahn & Albersheim ’78, Robertsen et al ’94, Song & Hsieh ‘94).
These micro-organisms have always been a threat to animal species, and so the innate immune system long ago developed the ability to recognise 1-3, 1-6 beta glucans and react to them by mounting an immune response. But it went further than that. As yeasts are so universal, the innate immune system actually became acclimatised to them, and dependent on them to function at peak effectiveness.
Then very late in the evolutionary day, modern technology effectively sterilised our food chain and much of our environment. Levels of yeast and other fungi in our foods, on our bodies and in our houses dropped away; and left the innate immune system weaker. This is the so-called ‘Hygiene’ hypothesis referred to above.
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Adding 1-3, 1-6 beta glucans back into the diet restores the effectiveness of the innate immune system, with considerable health benefits.
The following sequence explains how 1-3, 1-6 beta glucans prime the immune system to work at a higher level of activity.
A biological Guided missile – how Beta Glucan 3-6 works
In the Peyer’s patches, the beta glucan molecules are encountered by circulating macrophages – immune cells whose function is to engulf and digest foreign invaders – whether bacterial, fungal or viral.
Macrophages have receptors which specifically recognise 1-3, 1-6 beta glucans (Czop & Austen ’85), because they occur in the cell walls of many bacteria and fungi. This means that when you ingest beta glucans your innate immune system thinks, not unreasonably, that an enemy has arrived and it rises to the challenge.
This important first line of defence is now fully activated, and several well-conducted research papers have shown that resistance to infection is greatly enhanced (Onderdonk et al ’92, Kernodle et al ’98, Vetvicka et al ‘02).
2. Specialised cells called M-Cells transport the whole glucan particles to macrophages and these macrophages, in turn, convey the whole glucan particles to various regions of the immune system – such as lymph nodes, bone marrow and the Thymus. Figure 2
3. The macrophages then breakdown the beta glucans 1-3, 1-6 into smaller particles. These active fragments bind or lock onto the surface of neutrophils – which are the most abundant immune cells in the body.
They then lock on to a receptor called CR3 – Complement Receptor 3. Figure 3
The neutrophil is now activated or ‘primed’ and ready to seek out foreign challengers or pathogens.
4. For a neutrophil to kill a foreign challenger – or pathogen – the CR3 receptor (Complement Receptor 3) must be occupied by both complement – a blood protein – and beta glucan.
The CR3 receptor is occupied naturally by moulds and yeasts . But there are other threats, including bacteria, viruses and cancer, where beta glucan is not present.
Thus, by taking beta glucans, the neutrophils are provided with the missing element they need to trigger the neutrophil’s natural killing mechanism
5. A fully primed neutrophil now migrates to the site of a pathogen (whether virus, cancer or bacterium) through a process called chemotaxis.
The neutrophil then binds to the surface of this pathogen – and recognises it as ‘non-self’ ie foreign. It is now able to destroy that pathogen by releasing toxic chemicals Figure 4
6. At the same time, other killer cells retain fragments of the pathogens (ie. foreign invaders) that they have destroyed and ‘present’ them on their surface. These send signals to other members of the immune system family, which become memory cells.
Next time the same virus or pathogen is encountered, these newly programmed memory cells will recognise the virus and produce antibodies. These antibodies stick to the surface of the virus and prevent it from infecting healthy cells.
7. Size matters. The molecular size of the beta glucans also appears to be important. Particles of approximately 2-6 microns in size appear to be most effective.
Beta glucans are supplements derived and purified from the cell walls of common baker’s yeast (Saccharomyces cerevisiae). Research has shown that critical cellular components of the human immune system – macrophages, neutrophils and natural killer (NK) cells have specific receptors for the beta glucan molecule.
Studies that support the efficacy of beta glucans (referenced below) originated with laboratory experiments – for example, in one study 90 % of mice exposed to very high levels of E-coli survived when their innate immune systems were primed by 1-3, 1-6 beta-glucans. 0% survived in the control group in another mice study the administration of glucan before lethal irradiation (900 rads) enhanced survival. The most significant results were seen when glucan was administered 1 day prior to irradiation. .
In a further test, 80% survived exposure to high levels of Staphylococcus aureus as opposed to 0% in the control group.
When beta glucans were administered in combination with anti-biotics after exposure to bacteria, the number of bacteria needed to actually create infection was increased up to 2,000 fold
A recent human study demonstrated that a beta glucan supplement significantly increased the number of immune cells that were actively engulfing and destroying foreign particles or intruders. After 10 days of treatment, the supplement had increased the percentage of immune cells able to phagocytose (or “eat”) pathogens from 37.3% to more than 50%.
These results show that taking beta glucans enhances the human immune system to defend the body against a challenge. Additionally, the numbers of several important cytokines (proteins which support immune function) were increased.
Beta glucans can be taken by anyone wanting to maintain or enhance the effectiveness of their immune system. That includes anyone who experiences daily stress (which lowers the immune response), people who are at risk of infectious diseases, or are experiencing slow and incomplete healing. Amateur and professional athletes may also derive benefits from beta glucans, since intensive training can actually lower the immune response. They are best taken on an empty stomach 30 mins before food, three times a day. Increased dosages according to body weight may be desired for serious health challenges.
The peyer’s patches cells only seem to be receptive at certain times of the day and this seems to coincide with an empty stomach, it may also be due to the fact that these patches are at the very end of the small intestine and would normally be covered with waste materials which aren’t absorbed and need an uncluttered access to the beta glucan molecules which might pass by first.
It is reported that enterocytes facilitate the transportation of β(1,3)-glucans and similar compounds across the intestinal cell wall into the lymph, where they begin to interact with macrophages to activate immune function. Radio-labeled studies have verified that both small and large fragments of β-glucans are found in the serum, which indicates that they are absorbed from the intestinal tract. M cells within the Peyer’s patches physically transport the insoluble whole glucan particles into the gut-associated lymphoid tissue.
Additional circumstances for use would include people entering hospital – who are at greater risk of infection – as are long distance air travelers, who are exposed to higher levels of radiation. There are encouraging preliminary studies indicating that 1-3, 1-6 beta glucans can be used synergistically with monoclonal anti-body cancer treatment to increase effectiveness and reduce side effects.
Ideally, beta glucans should be taken as a daily supplement in periods of stress or threat, because the immune system’s effectiveness fluctuates from day to day and the life cycle of neutrophils is short – less than 2/3 days.
Beta Glucans and Cancer
There are several positive effects of beta glucan in tumor therapy. One is the direct positive enhancement of macrophages and NK cells. Macrophages form the first line of defense and protect our body against any type of invaders – including cancer cells. NK cells represent a special subtype of “bloodthirsty” lymphocytes, with a single but extremely important function – to specifically recognize and kill tumor cells. The job of these cells isn’t easy, considering the fact that they perform this function 24 hours a day, seven days a week. Again, they can use all the help they can get.
Recent animal studies have shown that beta glucan is extremely active in cooperation with antibodies, which naturally occur in case of cancer. This is one way that tumor cells are recognized by the immune system. Even a healthy immune system cannot adequately deal with fast-growing cancer cells alone and the situation can get serious very fast.
Antibodies alone cannot make tumor cells disappear, but following the binding of antibodies and a blood protein called complement on the surface of cancer cells, beta glucan-primed immune cells specifically recognize these complement-antibody complexes and kill the tumor cells. The cooperation of antibodies with beta glucan is more active than either irradiation or chemotherapy. Compared to traditional treatment of cancer, this type of treatment has one big advantage – it acts without any negative side effects.
Despite the fact that most tumors are recognized by the immune system, the antibody response is usually only light and often not strong enough to destroy the cancer growth. Again, beta glucan comes to the rescue. It is able to “cooperate” with antibodies. After tumor cells are recognized as foreign, antibodies specific to that cancer are formed, and subsequently bind to the cancer cells. Without the beta glucan-derived activation of immune cells, the cancer cells remain coated, but no killing occurs.
Beta glucan binds to the surface of both macrophages and NK cells, interacts with the surface molecules, and triggers the activation processes. The result of this interaction is that the highly activated tumor killers circulate in our body and actively seek and destroy their preferred targets – cancer cells. Upon contact with these cancer cells they kill them in a specific way, which means they destroy only the cancer cells and leave the surrounding tissues and organs remains intact and unharmed.
The miraculous effects of beta glucan do not end in activation of immunocytes. Beside the ability to stimulate the cells of the immune system to perform optimally and maximally, beta glucan also “cares” about their numbers. It is well established that all cells involved in immune reactions originate from common precursors – stem cells originating from bone marrow. The influx of new cells from bone marrow is steady throughout our entire life.
Beta glucan stimulates the production of precursor cells in bone marrow, resulting in a more rapid flow of new immunocytes into the bloodstream and into the various lymphoid organs throughout the body. These effects are important not only under normal conditions, as the increased amount of immunocytes in circulation means increased surveillance against potential invaders, but particularly in case of extreme stress such as cancer, where the limited influx is further reduced by exhaustion of the immune system and by treatments such as irradiation and chemotherapy.
These effects alone would be enough to consider beta glucan one of the most significant anti-cancerous immunostimulants we know, but beta glucan has still another ace up its sleeve. In addition to the already mentioned specific stimulation of cell surface receptors, beta glucan is able to nonspecifically activate of the immune system via the release of biologically important molecules.
Upon entering the blood stream, beta glucan activates various cells of the body to release numerous biological factors and signals molecules known to influence our defensive systems. Among these factors are: tumor necrosis factor (TNF), interleukins 1 and 6, hydrogen peroxide, and gamma interferon, all of which are proven effective in our fight against cancers and other invading microorganisms.
These effects are systemic, which means that even after localized application of glucan, these immunoactive molecules can influence the activity of immune system throughout the entire human body. In addition to the direct effects on tumor cells, the synthesis and release of these signals also has a direct impact on macrophages and T lymphocytes capable of producing other cytokines. In this nonspecific way, beta glucan helps to boost defensive reactions by triggering the whole complicated cascade of events leading to a fully armed immune system.
Vitamin D – activating natural killer cells
Depletion of Vitamin D in the body has long been known as a key contributory factor to the common problems of osteoporosis and osteopenia (loss of bone density). More recently, D depletion has also been shown to reduce the effectiveness of the innate immune system – the first line of defence against bacterial and viral invaders.
A gene named Vitamin D3-Upregulated Protein 1 (VDUP1) takes a vital part in giving directions to stem cells to expand into natural killer cells, one of the key elements in the innate immune system, and whose function is to seek and destroy virus-infected cells.
If you are low in vitamin D, (and reduced exposure to sun in the northern hemisphere which means we tend to be) fewer numbers of natural killer cells are formed and your innate immune defence against viruses becomes impaired. Since the other function of natural killer cells is to kill tumour cells, Vitamin D-depletion also increases our risk of cancer. Get 10,000iu capsules of Vitamin D3 here
Selenium deficiency in the body weakens resistance to invading viruses
Selenium deficiency allows invading viruses to mutate and remain for a longer period in the host. Researchers at the University of North Carolina compared mice that received a selenium-deficient diet with non-deficient animals, all of which were exposed to the human influenza virus. The deficient mice had more severe cases of the flu and it lasted for a longer period of time than the non-deficient mice.
Selenium deficiency has become a prominent dietary factor contributing to an increased risk of infection. It is prevalent in large parts of the world, including the UK.
Beta sitosterols – an important immune modulator
The nutritional plant extract beta sitosterol is an example of a group of molecules called sterols. They are regarded as the plant kingdom’s equivalent of cholesterol. Beta sitosterol is a natural immuno-modulator as it up-regulates (enhances) certain aspects of immune function while down-regulating others. Hence, a diet rich in sterols can ‘quieten’ unwanted auto-immune responses and improve desired immune response.
Beta sitosterol increases natural killer cell activity, so depletion leaves the cells under-active. This contributes to an overall degradation of the innate immune system. It is present in a large number of plant foods and especially seeds and nuts
The safety of any supplement – or treatment – has to be the first priority. Since beta sitosterol and beta glucans are natural supplements derived from food, they are safe for people of all ages, except for people who have had an organ transplant.
Indeed food derived nutrients are, in principle, normally safer than artificially created pharmaceutical drug molecules, precisely because they are natural and have been consumed for centuries.
Dr. Paul R Clayton
Beta Glucan & Immuno Primers
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