Immuno-Primers - powerful new activators for the Immune System

‘Give me spots on my apples, but leave me the birds and the bees, please!’ (From Big Yellow Taxi by Joni Mitchell, 1970).

Joni was more right than she, or we, knew. 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.

To compound the problem, we have over-sanitised our environment, through the wide-spread use of fungicides and bactericidal household sprays. (This is known as the hygiene hypothesis – and it is supported by the fact that children with pets do tend to have stronger immune systems).

Consequently we have left our immune systems less effective at defending us against bacteria and viruses - and we are more likely to develop allergic symptoms.

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.

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. It is provided by Biothera – a leading company in the research of yeast-derived beta glucans and the manufacturer of a refined and patented source of 1-3, 1-6 beta glucans (WGP 3-6).

Biothera’s WGP 3-6 has been subjected to a significant number of clinical trials and has recently been chosen by the US Government for trials in situations where the public may face radiation hazards, whether accidental or deliberate.

A biological Guided missile - how WGP 3-6 works

figure_11. Once swallowed, whole beta glucans particles pass through the stomach into the small intestine where they are taken up by specialised regions called the Peyer’s Patches.

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.figure_2

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

figure_3The 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 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.

Research results

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 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.

Recommended use

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.

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.

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 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, D-depletion also increases our risk of cancer.

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

Safety

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.

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

Disclosure: I have advised on the formulation of Uni-Vite ImmunoShield, a natural nutritional immune system booster containing a combination of WGP 3-6 beta glucans supplied by Biothera and beta sitosterol, another immune modulator.


  References
 

de Felippe JJ, da Rocha-Silva FM, Maciel FM, Soares A de M, Mendes NF. Infection prevention in patients with severe multiple trauma with the immunomodulator beta 1-3 polyglucose (glucan). Surgery, Gynecology and Obstetrics 1993;177(4): 383-388.

Patchen ML, McVittie TJ. Stimulated hemopoesis and enhanced survival following glucan treatment in sublethally and lethally irradiated mice. Int J Immunopharmac 1985; 7: 923-932.

Bouic PJ, Etsebeth S, Liebenberg RW, Albrecht CF, Pegel K, Van Jaarsveld PP. Beta-sitosterol and beta-sitosterol glucoside stimulate human peripheral blood lymphocyte proliferation: implications for their use as an immunomodulatory combination. Int J Immunopharmacol 1996 Dec;18(12):693-700

Patchen ML, D'Alesandro MM, Brook I, Blakely WF, McVittie TJ. Glucan: mechanisms involved in its "radioprotective" effect. J Leuc Biol 1987; 42: 95-105.

Vetvicka V, Terayama K, Mandeville R, Brousseau P, Kournikakis B, Ostroff G. Pilot Study:Orally-Administered Yeast Beta1,3-glucan Prophylactically Protects Against Anthrax Infection and Cancer in Mice. J Am Nutraceutical Assocn 2002; 5: 1-5.

Babineau TJ, Hackford A, Kenler A, Bistrian B, Forse RA, Fairchild PG, Heard S, Keroack M, Caushaj P, Benotti P. A phase II multicenter, double-blind, randomized, placebo-controlled study of three dosages of an immunomodulator (PGG-glucan) in high-risk surgical patients. Arch Surg. 1994 Nov;129(11):1204-10.

Beck MA, Levander OA, Handy J. Selenium Deficiency and Viral Infection. J Nutr. 2003;133(5):1463S-1467S

Chandra RK. Effect of vitamin and trace-element supplementation on immune responses and infection in elderly subjects. Lancet 1992; 340:1124-1127..

Di Luzio NR, Williams DL. The role of glucan in the prevention and modification of microparasitic diseases. In: Assessments of chemical regulation of immunity in veterinary medici Di Luzio NR, Williams DL.

Rasmussen LT and Seljelid R. Novel Immunomodulators With Pronounced In Vitro Effects Caused by Stimulation of Cytokine Release. J Cell Biochem 1991; 46:60-68. Quote: "Beta-1, 3-D-polyglucose derivatives protect mice against otherwise lethal bacterial infections."

Tzianabos AO, Cisneros RL. Prophylaxis with the immunomodulator PGG glucan enhances antibiotic efficacy in rats infected with antibiotic-resistant bacteria. Ann NY Acad Sci Oct 1996; 797: 285-287.

Williams DL et al. Protective Effect of Glucan in Experimentally Induced Candidiasis. J Reticuloendothel Soc 1978; 23: 479-490.