Reprogramming the Immune System – where conventional and complementary medicine can come together

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Contents

(By Dr Sarah Myhill and Craig Robinson)

Preliminary thoughts

I think of the immune system as a “mobile brain” in that it displays common features to those of the brain. Both the brain and immune system are intelligent, capable of making decisions, hold memory and each can solve “problems”. They are both susceptible to and employ the same hormones and neuro-transmitters. Cells of the immune system are soft (they are contained within the bony “skull” of long bones) and they are loving of fat – bone marrow and brain matter are both delicate, friable materials.

The immune system has to be clever, just as most brains have to be! The immune system’s cleverness is not demonstrated through its ability to solve algebraic equations though, but rather through its ability to distinguish between “good” and “bad” and mount an appropriate response, a much trickier and more finely balanced task.

The immune system is our standing army. It is enormously demanding of energy and raw materials. We need it to fight battles against foreigners from outside. However the immune system, just like the brain, can get its wired crossed. If the immune system is inappropriately switched on then there is the potential for disaster.

The immune system has huge potential to punch an immunological hole in our energy bucket – we all know this – give a healthy person a dose of ‘flu and they will be bed bound. We need the immune system to fight infection but switching the immune system on is the last resort for the body and, I suspect, is symptomatic of a failure in other departments, (e.g. damaged skin, inadequate stomach acid, poor mucous production and so on). Problems arise when the immune system will not, or cannot, switch itself off - this results in inappropriate reactions. Clinically we call this allergy and auto-immunity. But I suspect other battles, hitherto unrecognised, are on-going reactions against microbes which would normally be allowed to lie dormant.

We imagine our bodies to be completely free from other microbes (infection). But this is not the case. Firstly the gut is teeming with bacteria, yeast and viruses - indeed if we were to total all the cells in the body then bacteria would outnumber human cells by ten to one. These bacterial cells are constantly leaking into the blood stream and this process is called bacterial translocation. Please see Bacterial translocation from the gastrointestinal tract. Even human DNA is not pristine –the human genome carries about 100,000 pieces of DNA that come from retroviruses, known as endogenous retroviruses. All told, these add up to an estimated 5-8% of the entire human genome - that is several times more DNA than makes up all 20,000 of our protein coding genes. Please see - Our Inner Viruses: Forty Million Years In the Making

The immune system cannot “kill” all these microbes - it would end up killing the host ie you and me. It has to do deals with them – you leave me alone and I will leave you alone. I suspect many CFSs have inappropriate on-going reactions against gut flora and viruses when their immune systems should really be doing deals with these microbes. One example we all know about is the chicken pox virus - once infected with this, the virus lies dormant causing no trouble, for years. However it can flare as shingles. Typically this happens if our immune system becomes less vigilant or “gets its wires crossed”. Possibly for the same reason, I suspect Epstein Barr Virus (EBV, otherwise known as glandular fever or infectious mononucleosis, or "mono") can cause a low grade chronic reaction that makes people ill – please see Wikipedia article on Chickenpox and Chronic Viral Presence in CFS/ME

So how do we switch off an inappropriate chronic response to the immune system?

My ideas for this come from the treatment of polymyalgia rheumatic and temporal arteritis. These conditions are clearly pro-inflammatory and are highly damaging to self. They are useless and self –destructive immune reactions. These conditions are both effectively treated with steroids, drugs which, in this context, have the effect of putting the immune system into a “straitjacket”. It is not allowed to react! However what is interesting is that after several months of use, these drugs can slowly be tailed off and the patient is cured. So we must ask ourselves what is the mechanism of this? How does this happen?

                        “Things do not [just] happen. Things are made to happen.”
                                                                                        John F. Kennedy

(HISTORICAL NOTE - The straitjacket was invented in France in 1790 by an upholsterer named Guilleret, for Bicêtre Hospital and was first known as Camisole de Force. Some camisole! )

Let us start from the very beginning - how are our immune cells programmed to learn what is right and what is wrong?

I suspect that the immune system learns, just as all other biological systems learn, i.e. on the apprenticeship system. The immature immune system that we are born with is initially programmed by Mother. It is programmed to accept whatever Mother offers the baby as being safe. The biggest two factors in this are diet and gut flora. Mother should be eating a Stone Age diet, meaning that those antigens spill over into breast milk and the baby learns to accept those as the norm. The same is true of gut flora – the foetal gut starts to be inoculated even across the placenta whilst in utero and then there is a further large inoculation at the moment of birth. Indeed we know these first 24 hours after birth are a critical window of time for this education to take place. These microbes are then fed friendly foods from breast milk and so the gut is colonised with friendly bacteria. In its plastic learning state the baby’s immune system accepts all this as the norm.

90% of the immune system is gut associated and these mature, grown up cells at the “coal face” know what they must and must not react to. Immature adolescent immune cells are released on a daily basis from the bone marrow into the blood stream and they learn from the “grown-ups” (i.e. the already existing immune cells). They learn to tolerate the status quo, they too become mature cells and so immune memory is passed down through the generations and maintained in this way. This explains the mechanism of on-going immune tolerance to gut microbes and food – ie most of the time we ignore these antigens and do not react against them as if they were viruses. We have learnt not to.

Western diets and lifestyles interfere with normal immune programming and tolerance

The problem with modern life is that it is pro-inflammatory and there are many factors which tend to switch the immune system on –

These all have the potential to switch the immune system on so that it loses its innate natural tolerance to foods, microbes and self. The problem is that this can become self-perpetuating. This is because those immature adolescent cells coming along behind the adults will copy them and so do the same. Immune tolerance is lost. This is disastrous civil war, damaging to the body, wasteful of precious energy and draining of raw materials.

This means that in such a state we need to employ a four pronged approach.

  • Firstly put the immune system in a straitjacket and stop these mature cells reacting. If this is done for a sufficient length of time (probably months - see below) then the immature cells coming along behind will learn not to react. They will again become immune tolerant.
  • Secondly use proven methods to switch off the immune system such as incremental desensitising injections, oral immunotherapy (food drops), probiotics (such as lactobacillus rhamnosus - please see Probiotics - lactobacillus rhamnosus ) and Enzyme Potentiated Desensitisation (EPD) and neutralisation - please see Enzyme Potentiated Desensitisation - how it works and Neutralisation
  • Thirdly avoid all those factors, in as much as one can, which are switching the immune system on.
  • Fourthly put in place all possible interventions to make the immune system less twitchy and prone to inflammation

Now to look at each prong in detail.......

Straitjacket examples include:

Imuno-suppressives such as

  • Steroids for auto-immune conditions rheumatoid arthritis, lupus.
  • Steroids for polymyalgia rheumatic, temporal arteritis, which I suspect results from allergy to gut microbes
  • Steroids for severe allergies such as asthma, ulcerative colitis, Crohn’s disease.
  • Anti-inflammatory drugs such as NSAIs
  • Antihistamines for chronic urticaria
  • Immunosupressives such as methotrexate, entanercept and gold injections for rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and juvenile idiopathic arthritis (all of which I suspect are allergies primarily to gut flora)
  • Rituximab for CFS and inflammatory arthritides – I do not recommend Rituximab for the treatment of CFS at this current time (one of the side-effects is death!) but one can infer the need for immune system re-programming from the results of its use. Please see Energy Expenditure in ME/CFS: Immune wastage of energy and Rituximab
  • Female sex hormones – these are immunosuppressive and straitjacket the immune system during pregnancy. This prevents Mother from rejecting Baby as a foreign body (genetically Baby is, well less than 50%, Dad – less than 50% because the mitochondria are all Mum). Mums often reduce their allergies during pregnancy and feel well as a result!

Antimicrobials to reduce the infectious load so the immune system switches itself off

However, all the time it should be remembered that putting the immune system in a straitjacket is potentially dangerous – it may impair the normal efficient response to infection as well as impairing normal cancer surveillance. Any such intervention should be done for as short a time as possible.

Switch the immune system off

Incremental immunotherapy has long been recognised as being effective in inducing immune tolerance. The idea here is that one gradually increases the dose of antigen from a very low to a very high level over a period of time – typically two to three months – the immune system learns immune tolerance because the mature cells are not activated by a sudden hike in antigen.

Other immunotherapy techniques which have been shown to be effective include EPD (enzyme potentiated desensitisation), neutralisation and oral immunotherapy (food drops) - again the time scale for many of these is 6 months to a year for them to be effective. The “apprenticeship” of new immune cells often takes this long to become the norm. Please see - Enzyme Potentiated Desensitisation - how it works , Neutralisation and Oral immunotherapy: switching off food allergies using food.

Do not switch the immune system on

Some interventions are a red rag to the bull as far as the immune system is concerned. The obvious examples are

  • viral infection - EBV is particularly good at switching the immune system on
  • vaccination,
  • sugar and carbohydrates,
  • tissue damage (from trauma, accidents or over training),
  • strong antigens, (e.g. gluten and casein)
  • unnecessary infections e.g. from foreign travel and
  • sexually transmitted disease
  • pollutants - such as diesel particulates, pesticides, heavy metals (nickel, mercury and aluminium possbly others)
  • silicones - eg breast implants, surgical prostheses
  • mood - it may be that an angry brain results in an angry immune system!

Make the immune system less prone to inflammation

The immune system, when inflamed, has a momentum of its own – I think of this as a pro-inflammatory fire (please see Inflammation ). This fire can be damped down with anti-oxidants such as:-

  • Improving front-line antioxidant status:- superoxide dismutase, co-enzyme Q10 and glutathione peroxidase – please see Antioxidants
  • Vitamin D3 – please see Vitamin D
  • Vitamin C
  • High dose vitamin B12 by injection – please see B12 - rationale for using vitamin B12 in CFS
  • Low dose naltrexone
  • Worms - these are of proven benefit in inflammatory bowel disease

Cautionary Note

I think it is important to recognise that for the above to be effective the patient needs to be as free from symptoms as possible. If patients are not free from symptoms, then the immune system is active and reacting and, therefore, not being educated “the right way” – i.e. towards being less prone to inflammation. If the patient is experiencing symptoms then immune system education is all going in the wrong direction – ie it is pro-inflammatory.

This means that the dose of any drug must be very carefully balanced. Too little and the education is incorrect or “not enough”, too much and the immune suppression occurs with all its risk of resulting overwhelming infection, poor cancer surveillance and so on.

                                       “Too much of a good thing can be a bad thing”
                                                                          Old English saying

(Deriving from Proverbs 25:16 – “Hast thou found honey? Eat so much as is sufficient for thee, lest thou be filled therewith and vomit it”)

I think one has to be additionally cautious using symptom suppressing medication – it is all too tempting to overdo things – remember cell damage from not pacing well (which may be a “human” consequence of suppressing symptoms i.e one feels better and so one feels one can do more) will also activate the immune system. It is only by a clear understanding of the above principles that the individual patient can balance up the treatments to maximise benefit with the lowest possible dose of drug in the shortest possible time (and the shortest time will be several months).

The above mechanism may not be proven but it is a biologically plausible mechanism which has clearly passed the clinical test of time! It may well be that there are some years before the science catches up but this is characteristic of the development of new ideas in a clinical setting.

Summary

To re-programme the immune system we have to think about how it is programmed in the first place. Therefore, we have a two pronged approach over and above all else to try to re-programme the immune system:-

  • Use drugs, nutritional supplements or whatever to straitjacket the immune system so that it stops reacting. We have to stop it doing wrong and highly damaging things
  • Encourage immune tolerance. This may happen simply with time. But perhaps in parallel with this use a desensitisation technique.

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