Posts Tagged ‘immunity’

When Leonard Noon reported his first tentative experiments with immunotherapy for hayfever, in 1911 (see p. 164), he believed that pollen contained a toxin. Most people were

‘immune’ to this toxin, he said, in the same way that people might be immune to measles or diphtheria, but hayfever sufferers lacked this immunity. Noon thought that his

steadily increasing doses of pollen, injected just under the skin, were inducing immunity to the pollen toxin, in the same way that a smallpox vaccine could induce immunity to

smallpox.
Noon’s theory was all wrong, as we now know, but the important thing was that the treatment seemed to work. In fact it transformed the lives of some patients, especially those

who were very severely affected by hayfever. One spoke of a ‘marvellous cure’, another of going for walks to kick my old enemy the hay’.
So doctors kept using Noon’s treatment, and in time — when it became clear that Noon’s theory was flawed — medical researchers began trying to figure out how the injections

really worked.
Surprisingly, they have still not succeeded, even though a great deal is now known about the changes that can occur in people undergoing immunotherapy. Despite a wealth of

detailed knowledge (see p. 166), it remains impossible to say exactly how conventional immunotherapy reduces allergic reactions. Surprising discoveries about the effects of

conventional immunotherapy are being made all the time.
New methods of immunotherapy are still being devised today, and there are three different approaches being taken.
Firstly, there are doctors experimenting with modifications of the technique devised by Noon. For example, instead of injecting the allergen extract, some doctors are giving it

to their patients in capsule form. to be swallowed. Others are giving it as a liquid, to be placed under the tongue and held there for a few minutes, then swallowed (see p.

169). Sound scientific trials show that both these methods work well, at least with some allergens.
There are also experiments with speeded-up immunotherapy
(see p. 166), called ultrarush techniques — at the outset, injections are given at hourly intervals, or even more frequently (in hospital, of course, where severe reactions can

be dealt with immediately). Doctors have found that they can induce a remarkably rapid tolerance of the allergen in this way.
The second approach is to apply modern medical knowledge about allergic reactions and so develop entirely new methods of immunotherapy (see p. 168-9). Such research involves

working out, from first principles, novel ways of modifying the immune response in general, or the reaction to one allergen in particular.
This theory-led approach is certainly successful for classical allergies such as hayfever and perennial allergic rhinitis, where there is a good understanding of the basic

mechanism (i.e. the malfunctions of the immune system that produce the disease). But for those diseases where the underlying mechanism is only partially understood, such as

atopic eczema, this approach is not necessarily the best one. And for diseases such as food intolerance, where the cause of the illness remains largely unknown, it is a complete

non-starter.
The third type of approach is to devise a technique by trial and error, and then puzzle out the ‘how’ question later. This is the same sort of path as Noon originally took, and

some believe that this kind of pragmatic experimental approach — practising a method which seems to be effective, even though it’s a mystery how it works — is as valid now as it

was in 1911. Others disagree.
210 complementary therapies The two most widely used methods that have been developed in this way are Provocation-Neutralisation and Enzyme- Potentiated Desensitisation.

Although these techniques are practised by doctors with a conventional medical training, they remain ‘outside the pale’ as far as orthodox medicine is concerned. The

controversies that surround them are discussed below.
Enzyme- Potentiated Desensitisation (EPD)
This technique has been developed by a British doctor, Dr Len McEwen, who began work on it in the 1960s. It is now practised in many parts of the world, as well as Britain,

including the United States, Germany and Italy.
EPD is used for a far wider range of problems than conventional immunotherapy, being given to people with food intolerance and chemical intolerance, as well as to those with

true allergies. This — along with the fact that it is unclear how it works —contributes to the controversies that surround it, because these conditions do not have the same

basic causes.
Dr McEwen began with the observation that, when immune cells are aroused during inflammation — whether caused by allergy or some other stimulus — they release large amounts of

an enzyme called beta-glucuronidase. This enzyme increases the immune response to the allergen or antigen that provoked the inflammation.
Dr McEwen experimented with injecting beta-glucuronidase into the skin, along with very small amounts of allergen, believing that in such circumstances the enzyme might have the

opposite effect, and reduce the immune reaction to the allergen. Eventually he discovered a combination of enzyme and allergen which seemed to have the desired effect.
EPD has been tested, in a rigorous scientific manner, and the results suggest that it can work for hayfever and asthma, as well as for childhood migraine and hyperactivity in

children when these are triggered by foods.
In one trial with hayfever patients, researchers measured the levels of anti-pollen IgE following EPD treatment, and it did not rise during the pollen season as it normally does

in those with hayfever. This kind of finding is impressive because it is unlikely to be due to placebo effect. Not all studies have produced positive results, however.
In addition, doctors using EPD claim that it is very effective for patients with allergies who have not done well on the standard course of immunotherapy injections (see p.

164). This fits in with other studies suggesting that the immune changes brought about by EPD are fundamentally different from those induced by traditional immunotherapy.
Patients with true food allergy have been given EPD, and while it does not enable them to eat their culprit food, it does
seem to reduce their reaction to accidental exposures.
Doctors in the Netherlands are using EPD as a treatment for people with Chronic Fatigue Syndrome (CFS), and report that it helps about 50% of patients.
One point in favour of EPD is that it uses very small amounts of allergen, and is therefore very safe — anaphylaxis has never occurred with this technique.
Provocation-Neutralisation
‘After following conventional methods [of immunotherapy] for thirteen years, I heard Carleton H. Lee deliver a paper on provocative testing in 1965, at a meeting of the American

College of Allergists in Chicago. I was naturally sceptical, but tried his suggestions when I returned to my office. The results can only be described as astounding. Many

patients with unresolved allergic problems responded markedly and rapidly. Many with resistant asthma or perennial allergic rhinitis improved greatly or cleared completely when

food injection therapy was added to their inhalant injection therapy.’ So wrote Dr Joseph B. Miller — a distinguished allergist and paediatrician, and a Professor of Medicine at

the University of Alabama, in 1972.
The technique which he learned from Carleton H. Lee was controversial then and, although Miller developed it with great care and precision during the years that followed, it

remains controversial now.
There are two elements in provocation - neutralisation: testing and treatment. Both are used for a wide range of problems — not just classical allergic diseases, but also food

intolerance and chemical intolerance. As with EPD (see left), this is one of the controversial aspects of the technique.
Although provocation-neutralisation involves an injection technique that looks, superficially, very much like conventional immunotherapy (see p. 164), there are several

important differences. Firstly, the allergen extract used (in the case of true allergies) is a very dilute extract, so that far less of the allergen is injected than in

conventional immunotherapy. Likewise, in the case of food intolerance and chemical intolerance, the extracts of the offending substance are used in highly dilute form.
Secondly, the idea of the neutralising dose — which is the central plank of provocation-neutralisation — is quite different from anything in conventional immunotherapy. Broadly

speaking, the conventional technique (see pp. 165-6) works by slowly reeducating the immune system with a gradually increasing dose of the allergen. Only after a succession of

injections does the immune system start to behave differently on encountering the allergen. By contrast, in provocation-neutralisation treatment, the neutralising dose is

claimed to have an instantaneous and direct effect on the body, ‘turning off’ symptoms that have already begun. This is the neutralisation aspect of the technique. The doctors

who practise this technique do not claim to know how the neutralising dose might work.
According to the theory of provocation-neutralisation, the strength of the extract that acts as a neutralising dose is specific for a particular allergen and a particular

person. It can only be worked out by a rather slow procedure involving a series of injections. These are intradermal injections – they place the allergen extract in the skin, at

a slightly deeper level than a skin-prick test. (For treatment, rather than testing, subcutaneous injections are used – these go deeper than intradermal injections, placing the

allergen extract just underneath the skin. Neither hurts very much.)
Ideally, the neutralising dose should be decided on by measuring the size of the wheal (a raised area of skin around the injection site), and whether it grows, stays the same

size, or disappears. The doctor or nurse carrying out the procedure can, in theory, work out the neutralising dose just by careful examination of the skin wheals.
However, it is part of the tradition of provocation-neutralisation techniques that verbal feedback from the patient is also taken into account – so if the patient says that an

injection has turned off the symptoms, that reinforces the belief that the neutralising dose has been found.
The problem with this aspect of provocation-neutralisation is that expectations, and the power of suggestion, can become involved. So if the doctor or nurse says ‘you may find

that this next injection makes the symptoms go away’, that is often exactly what happens – because the forces of placebo effect (see p. 233) come into play. Unfortunately,

verbal interactions such as this are a key aspect of the provocation-neutralisation procedure in many clinics.
Just the same hazard besets provocation - neutralisation if it is used to test for the existence of allergy or intolerance, because it is quite common for practitioners to tell

patients which allergen (or other offending substance) is being injected and to ask if any symptoms are provoked by the injection. This is not good practice – if someone expects

to react to a particular substance, they are quite likely to produce symptoms through purely psychological mechanisms (see pp. 232-3).
Quite apart from this, the question of allergy testing with provocation-neutralisation techniques is contentious, because the pioneers of the technique, such as Professor

Miller, never advocated using provocation - neutralisation in this way. Using it as a routine test for sensitivity reactions was a later development, and there are many doctors

today who, while they practise provocation-neutralisation as a treatment, say that it does not work well as a test for sensitivity reactions. While they agree that injecting a

dose
which is either stronger or weaker than the neutralising dose may provoke actual symptoms (this is the provocation aspect of the technique) they don’t think the reaction is

reliable enough to form the basis of a test for allergies. Nor do they think that using skin-wheal measurements alone (i.e. silent testing) turns the technique into an accurate

test for allergies. That is not what the provocation-neutralisation technique was designed for – it is about treatment, not testing.
The evidence from research
Recent research from the Nova Scotia Environmental Health Centre in Canada confirms that testing by provocation injections is not reliable. The subjects in this study were all

suffering fr= multiple chemical intolerance, a condition which – for one reasor or another – makes patients liable to develop symptoms at an,, time. No less than 70% of these

patients experienced symptoms in response to a dummy injection which contained none of the offending substance. Indeed, 15% of patients also produced a skin wheal in response to

some of the dummy injections, confirming that even this reaction may be subject to the power of suggestion (see pp. 232-3).
Looking just at the patients who did not react to the placebo injection (i.e. those least susceptible to suggestion) the test still did not yield any reliable result – a person

might react to one injection with a particular substance, but fail to react to a subsequent injection with the same substance. The authors concluded that their patients were ‘in

a state of heightened sensitivity as the result of the chronic irritation by various environmental components and other external and internal stressors’. In this state of

sensitivity. patients are so close to the brink all the time that the smallest thing can trigger symptoms. So the apparent reactions to the test injections were actually

determined by other factors – some psychological factors (including a psychological response to the prick of the needle) and some external ones, such as exposure to smells or

very small amounts of airborne chemicals.
Another recent research study, carried out by scientists at the University of California, confirmed the finding of the Nova Scotia team as regards testing. Although this study

did not set out to look at the use of the neutralising dose for treatment, some of the patients were given neutralising doses during the testing process and the researchers

observed that ‘in most cases a single neutralising injection relieved the symptoms’. This casual observation clearly needs to be confirmed by more rigorous testing. Oddly

enough, despite this positive observation about the neutralising doses, the overall conclusion of the researchers was to completely dismiss all aspects of

provocation-neutralisation as ‘the result of suggestion and chance’. This conclusion has been widely publicised in the United States as part of a general campaign against

provocation-neutralisation and doctors who practise it.
Other researchers have looked at treatment with neutralising doses, using stringent scientific methods (a double-blind placebo-controlled trial — see p. 90), and found that they

do work. In one such trial, patients with asthma. and allergies to dogs or cats, were treated with injections of the neutralising dose. They showed a reduction in the

sensitivity of their airways, as measured by objective tests. In another experiment, patients with perennial allergic rhinitis and an allergy to house-dust mite were studied,

and the neutralising dose was given as drops of allergen extract placed under the tongue (sublingual drops) – an alternative to injections. The blockage of the nose, as measured

by scientific tests, was reduced by the neutralising dose.
A great many more trials of this kind would be required to convince most doctors that provocation-neutralisation works.
Furthermore, the recent study from California – which observed a number of practitioners of provocation-neutralisation at work with their patients — showed that these

practitioners need to be a lot more rigorous and objective in their approach. However, the fact that provocation-neutralisation is often practised badly does not necessarily

mean that the basic technique is without any value. There are a great many level-headed doctors and patients who, while initially very sceptical about

provocation-neutralisation, have found it surprisingly effective – just as Professor Miller did back in 1965.
Deciding for yourself
So is provocation-neutralisation an option that is worth trying for your condition?
As regards testing, the answer is probably ‘no’. The most reliable tests are skin-prick tests or FAST blood tests for true allergies (see pp. 91-2), an elimination diet for food

intolerance (see p. 194), and avoidance followed by re-exposure (a challenge test) for chemical intolerance.
As regards treatment for true allergies, conventional immunotherapy has been far more thoroughly tested and, if you can get it (not easy in Britain — see p. 164), is probably a

better bet. It is definitely the best treatment for allergy to insect stings.
The major advantage that provocation-neutralisation has over conventional immunotherapy, in the case of true allergies, is that it is far safer. Because such small amounts of

allergen are used, anaphylactic reactions (see p. 58) don’t occur.
When it comes to treatment for food intolerance, complete avoidance of the problem food(s), for a period of a year or two, is usually a very effective treatment (see p. 77).

Other forms of treatment are only needed for people who find that they have
intolerance to a great many different foods (on the basis of an elimination diet, not kinesiology, blood tests and the like — see p. 93) and cannot devise an adequate diet from

the foods they are able to eat. For such people, provocation-neutralisation may be worth a try. Many patients feel that they have gained considerable help from this treatment.

They report suffering fewer symptoms and being able to return to a more nutritionally balanced diet.
In the case of chemical intolerance, the first line of treatment should be to avoid the substances concerned as far as possible, eat a good balanced diet, and take a vitamin and

mineral supplement if nutritional deficiencies are suspected. Treating any underlying hyperventilation (see pp. 226-9) can also help considerably. Only if there are persistent

symptoms, and you are sure these are not due to psychological causes, might provocation-neutralisation be worth a try. Some people with chemical intolerance do find it is

helpful, but whether this is a real effect, or simply placebo, remains uncertain.
If you decide to give provocation-neutralisation a try, find a practitioner who has good medical qualifications, who seems objective and sensible in their approach, and who

doesn’t make implausible claims for the technique. Take note of what other treatments the practitioner offers, and whether these seem rational or not – this is often a good

guide to the care and objectivity with which provocation - neutralisation is carried out.
Ask the doctor how he or she assesses the neutralising dose. and avoid anyone who does not use the traditional method of a series of injections combined with wheal measurement.

When the neutralising dose is being assessed, say that you would like it to be done ’single-blind’ – that is, you don’t want to be told anything about what is being injected.

Reporting how you feel to the doctor or nurse during the assessment is fine, but only mention really significant symptoms, or a very definite clearance of the symptoms, if this

occurs. These precautions will help you to be sure that you are getting something which is of genuine benefit, rather than just a very expensive form of placebo treatment.
I always wanted to be a doctor, and I enjoyed
medical school immensely, but once I became a
ell GP, I no longer felt quite so sure about what I was doing. It seemed clear to me that there were a lot of people coming to my surgery who I couldn’t do much for. And there

were others who, while I could treat their obvious medical problems with some success, remained distressed and were not coping well with life. Once I became a senior partner in

this practice, I experimented with having a counsellor come in for one session a week, and then an osteopath for the bad backs. It was popular with the patients, and I saw some

people improve enormously. Now we have stress-management classes too, and one of my colleagues has trained in acupuncture, which he uses for selected patients. We also use

elimination diets for patients with a lot of long-term problems like migraine. Overall, I think of it in terms of having more tools at our disposal - being able to tackle things

from a different angle when standard medicine isn’t hitting the spot.’
Geoffrey, a GP in the north of England, is typical of the reconciliation that is now beginning to occur between conventional medicine and alternative medicine. But he also has

plenty of criticisms to make of the alternative scene. ‘The idea that alternative medicine is “holistic” while conventional medicine isn’t, really raises my hackles. Most GPs

could be magnificently holistic if they had an hour with each patient as alternative therapists usually do. We have just 15 minutes, on average, and we have to pack a lot into

that - including our basic duty to eliminate the possibility of serious organic disease such as cancer. Time pressure is everything now, and it has squeezed the humanity out of

medicine, to a very large extent. But the potential for a holistic approach is there - most doctors have a tremendous store of wisdom and life
experience at their disposal, which could form the basis of a holistic approach to treatment if only there were more time to spend with each patient.’
It is in search of a more unhurried and all-embracing approach to treatment that many people turn to alternative medicine. Frequently, what they get out of the therapy has less

to do with the actual methods used, and still less with the theories behind those methods, but everything to do with spending a quiet hour with someone supportive and caring who

listens to all the complex concerns that surround any illness, gives reassurance or advice, or just offers a `safe space’ in which to talk about life’s difficulties.
Other people turn to alternative therapies due to a more serious disillusionment with orthodox medicine. When patients with inscrutable medical problems -such as persistent

unexplained diarrhoea, joint pain or chronic urticaria - are given a succession of different diagnoses by different doctors, they often lose faith entirely in modern medicine

and reject orthodox treatment in favour of alternatives. This is a great mistake. Modern medicine isn’t perfect, but that is only to be expected, because it is not a fixed body

of knowledge but a process - a continuing journey of questioning, investigation, discovery and improvement. Scientific medicine has come a tremendously long way from the state

of ignorance that prevailed two centuries ago, and it will undoubtedly go farther.
Conventional medicine has a great deal going for it - ask anyone over 50, with severe life-long asthma, what they think of treatment now compared to treatment in the 1950s or

early 1960s. You will hear a hymn of praise to the improvements in both drugs and drug delivery systems. Asthma is just one example -conventional medicine has a lot to offer for

all the classical allergic diseases. Alternative medicine should always be regarded as an adjunct to conventional treatment, not a replacement. That is why many doctors prefer

the term complementary medicine.
A third reason for using alternative medicine is a more philosophical one, a need to understand illness in some larger sense, often part of a general search for meaning in life.

Some types of alternative treatment attempt to offer metaphysical reasons for allergy -rather than the mundane explanations of antibodies and immune cells that are given in this

book - and this can be attractive to some people. There is no harm in this approach, which can prompt you to make a critical review of your life, look at unresolved emotional

issues, or reassess choices that are making you unhappy.
But not all illness, or worsening symptoms, can be explained by emotional causes, and the rigid belief that every illness must have a meaning can be damaging. It easily

degenerates into the wholesale psychologisation of illness, the kind of blame-the-victim mentality which can attribute hayfever to ‘Emotional congestion; fear of the calendar; a

belief in persecution; guilt’ and asthma in babies to ‘Fear of life; not wanting to be here’. Both these diagnoses are taken from the best-selling You
can Heal your Life by Louise Hay, which is very influential among some alternative therapists. This compulsive psychologisation of illness can be profoundly damaging, and if

your complementary therapist is preoccupied by ideas of this kind, you could find yourself on a very long guilt trip indeed.
Apart from the psychological aspects of alternative medicine, there is the question of whether it actually works in a practical sense - whether it provides more than just

emotional support and placebo effect (the benefit that comes from any treatment which you believe in). This is always the central question for scientific medicine in relation to

its own treatments,
and conventional doctors naturally apply the same criteria to alternative medicine. Most of this chapter is concerned with trying to answer that question.
Unfortunately, there are so many different kinds of alternative therapy available today that it is impossible to cover all of them in this book. To complicate matters further,

many complementary therapists now practise two or more different techniques, mixing them to
produce their own unique cocktail of diagnosis and treatment. This eclectic approach can span a remarkable range - you may find a therapist doing distinctly whacky stuff such as

iridology (looking at the eye to diagnose all illness - it has been tested and definitely doesn’t work), combined with something perfectly rational such as an elimination diet.

(The elimination diet might be presented as a ‘detox diet’, but it is actually being used to detect food intolerances.)
With new forms of therapy springing up all over the place, a healthy scepticism is a distinct asset for the consumer. Be sceptical about any diagnostic test or treatment that is

only being practised by one person in the country, or in the world - when doctors hit on something that works, they want other doctors to try it out. World exclusives in

medicine are usually suspect.
Avoid any practitioner who tells you to stop using your drugs without your doctor’s consent. Likewise, avoid those with a messianic gleam in their eye, an evident disregard for

logic or reasonable discussion, or an amazing cure that fixes everything from acne to AIDS. Very few of those who sell bogus cures and phoney diagnostic tests are complete

rogues. Most are nice people who are quite genuinely convinced that they have indeed found the answer to people’s problems. The powers of placebo effect (see p. 233) can sustain

such a conviction for a very long time.

how does allergy begin?
A mast cell, magnified about 10,000 times. The black granules contain histamine.
`At the beginning, I thought I just had a cold. I kept sneezing and coughing, and my nose was dripping. It got better at the weekend, and I thought — that’s good, it’s gone — but then on the Monday evening it started up again. The next thing I knew, I kept getting breathless. I’d been at the sawmill a month when it began. We were cutting planks of red cedar all day, and the dust was bad, it’s true. But I didn’t know that sawdust could cause you allergies. We were given dust masks, but they made you too hot. No one wore them. I found out later, from the doctor, that some men could work years at it before they got allergic to the dust, but with me it was just a month.’
Like many people with work-related allergy, Dan can actually pinpoint the time he became sensitised – when he began making IgE antibodies against the red cedar dust allergen. For allergies that are not caused by workplace allergens, this is rarely possible. The moment when symptoms begin may be obvious, but that is often long after sensitisation (making IgE to the allergen) first occurred. Long-term studies of children show that they may start giving positive skin-prick tests to pollens (a sign that they are making IgE to those pollens) while they are toddlers, but not develop hayfever until ten years later.
The basics of immunity
The immune system defends the body against infections and cancerous cells. One of its key jobs, before going on the offensive, is to recognise the difference between:
• self and non-self (e.g. the cells lining the lung, and bacteria trying to infect the lung)
• safe-non-self (e.g. a sandwich) and dangerous-non-self (e.g. Salmonella bacteria in the sandwich).
Through mis-regulation the immune system can cause:
• allergies (perceiving safe-non-self, such as pollen, as dangerous-non-self)
• autoimmune diseases (perceiving self as non-self).
The immune system consists of dozens of different kinds of cells (the immune cells) and a number of different antibodies – specialised ‘guided missiles’ (see box on p. 15) which are produced by certain immune cells.
There is also a huge array of messenger chemicals, which send general instructions (e.g. ‘calm down!’, ‘go for it!’ or’exterminate!’) from one type of cell to another.
Immune cells are self-contained units, many of them mobile and dispersed throughout the body. They travel around in the blood, and can move out of the blood vessels and into the surrounding tissues (skin, lung, nose, etc.).
These different components – immune cells, antibodies and messenger chemicals – interact in very complex ways. When an immune reaction occurs – i.e. the immune system recognises something, or mounts an attack on something – numerous different players are involved. All the reactions described in this book are very simplified versions of what actually happens.
Research shows that the first two years of life is the most vulnerable time as regards sensitisation to allergens. Very often, sensitisation occurs in the first few months, and sometimes even before birth.
Why is a young infant so easily sensitised? The answer lies not with the baby, but with the pregnant mother-to-be, whose immune system has to overrule its natural inclination to attack anything that is non-self. Potentially, a woman’s immune system could reject a foetus in just the same way that heart transplants are rejected. To prevent attacks on the foetus, the immune system is re-tuned during pregnancy, with one aspect of immunity – the part that’s most keen to attack a foreign body – being damped down.
This aspect of immunity is coordinated by cells known as T-helper-1 cells, or Th1 cells for short. To protect the foetus, these Th1 cells are asked to ease up during pregnancy. Meanwhile, since immune protection is still needed, their colleagues, called T-helper-2 cells or Th2 cells, become more active.
The classical allergic diseases
These four pages are concerned only with the classical allergic diseases, that is:
hayfever (an allergy to pollen)
perennial allergic rhinitis (a nasal allergy to a year-round allergen such as house-dust mite)
asthma where this includes an allergic reaction atopic eczema (42)
urticaria (nettle rash or hives) where this is allergic in origin, and the accompanying angioedema (swelling due to fluid escaping from tiny blood vessels into the surrounding area; it is sometimes called ‘water retention’)
anaphylaxis (a violent allergic reaction to food, insect stings, penicillin, latex, etc.)
food allergy (in most cases, an immediate and marked reaction to food, with symptoms in the mouth; there may also be anaphylaxis).
Running the immune system
T-helper cells are, in a way, mis-named, because they do not help at all – they just give orders.
These are the supervisors of the immune reactions, telling other immune cells either to lie low or to get busy. Where Th1 and Th2 cells differ is in the types of immune cells they send into action. Among those who get their go-ahead from Th1 cells are immune cells that attack directly, without producing antibodies – these are the ones that reject transplants and could, if given free rein, reject a foetus or retard its growth.
The Th2 cells, on the other hand, have among their preferred troops the immune cells that produce IgE antibodies – the allergy-causing antibodies. So one effect of protecting the foetus from rejection is to push the immune system towards a greater tendency to allergy.
This shift of emphasis occurs in the mother’s immune system, but it carries over into the immune system of the foetus because they are sharing the same blood supply, and the blood contains the messenger substances which fine-tune the immune system. Immediately after birth, the baby’s immune system is still following the same pattern, continuing to upregulate Th2 cells and downregulate Th1 cells. This is a crucial factor in setting the stage for allergic sensitisation.
Ideally, the world that the baby encounters just after birth should nudge the immune system in the opposite direction and get it operating in a non-allergic way. But the world in which we live is far from ideal in this regard.
For one thing, it is much too clean. As far as the immune system is concerned, ‘ideal’ would mean encountering quite a bit of dirt, such as garden soil, in the early stages of life. The soil contains harmless bacteria which do not cause any symptoms, but do tweak the immune system towards Th1 cells and away from Th2 cells. Bacterial products in household dust may do the same thing (21).
A long period of consuming nothing but breast milk would also suit the baby’s immune system rather better than being fed on cow’s milk formula or being suddenly weaned onto a number of highly allergenic foods, such as egg, wheat, soya (ubiquitous in The basic cause of classical allergy is an immune reaction involving mast cells and IgE antibodies.
Mast cells are plentiful in the lining of the nose, the airways, and the digestive tract. They have counterparts in the blood, called basophils.
Seen under the microscope, both mast cells and basophils look very granular inside. The granules are tiny storage compartments, containing stockpiles of messenger chemicals, notably histamine.
Histamine causes several different reactions:
• contraction of muscle around the airways. This reduces the diameter of the airway, producing an asthma attack.
• widening of blood vessels
• increased leakiness of the smallest blood vessels, allowing fluid and immune cells to escape into the surrounding area – for example, the skin or airway lining
• as a result of these two above effects, local swelling (called oedema or angioedema) and irritation – in the skin this is experienced as urticaria, or nettle rash, in the nose it causes blockage, itching and sneezing
• if sufficient histamine is released into the blood, a drastic fall in blood pressure, due to widespread opening of blood vessels, and leakage of fluid into the tissues; this occurs in anaphylaxis (58).
Histamine is released when mast cells are activated, a process called degranulation because the cells discharge their storage granules.
Mast cells release other substances at the same time, some of which attract more immune cells to the area, causing more inflammation. They help to produce a ‘Late Phase Reaction’ which occurs after the initial allergic reaction has died down, and lasts about 24 hours (13). Once activated, mast cells also start making messenger chemicals called leukotrienes which are highly inflammatory.
What causes a mast cell to degranulate? The answer is found on the surface of the cells, where the allergy antibody, IgE, sits. One end of the IgE molecule is bound to the mast cell, and the other end can bind to the allergen concerned. In someone allergic to egg, for example, egg allergen will bind, with great specificity, to egg-specific IgE antibody.
For the receptors to pass a message to the mast cell there have to be two IgE antibodies specific for the same allergen on the mast cell – and the allergen has to bind to both these IgE molecules, cross-linking them. This is the ‘go’ signal for the mast cell to degranulate.
processed foods), fish or peanuts, before it can handle them. Not taking antibiotics before two years of age would also help (although it might, of course, be very bad for the baby in other ways). Exactly why is not yet fully understood .
An ideal world for the immune system would also lack the by-products of cigarette smoking, whether in the blood of a pregnant woman or in the air that a baby breathes – both seem to promote the allergic tendency. In addition, the perfect world would lack central heating, fitted carpets, draught-proofing and thick upholstery. A house like this is heaven for house-dust mites but not for innocent young immune systems.
The problem with house-dust mites – apart from the fact that they breed like wildfire, and hole-up in mattresses, armchairs and soft toys – is that they produce a highly allergenic protein in their droppings. This protein interferes with the membranes of cells, making them less stable. It irritates various immune cells, including mast cells (see box at left), and can even make mast cells degranulate, as if there were a true allergic reaction happening.
Once mast cells have done this, they release messenger substances that arouse the immune system and make a genuine allergic reaction –beginning with the production of IgE to the dust-mite allergen – much more likely. In other words, dust-mite allergen is an agent provocateur, an aggressive substance that actually provokes the immune system into reacting allergically.
Until recently it was widely assumed that allergens were just inoffensive, passive substances which the immune system happened to take objection to, in a distinctly unreasonable way. The new discoveries about dust-mite allergen raise the question: could other allergens be more aggressive than previously thought? Certainly the peanut allergen, or other substances found in peanuts, seems to destabilise cell membranes, which may explain why this allergen so easily sensitises young children.
The role of genes
Faced with this non-ideal world, many children pull through without developing allergies, but others do not. This is where genes come in, making one child more susceptible to our allergy-promoting lifestyle and another child less so. Exactly how the genes make this difference is still not fully understood, but there are at least twenty genes involved , and it is clearly going to be a complex story. The overall effect of these genes is a greater tendency to make IgE, combined with mast cells and basophils  that are distinctly trigger-happy –much more eager to degranulate than in healthy individuals.
Given all the mayhem caused by mast cells and IgE, why does the body produce them at all? They cause a lot of damage to allergy sufferers and do little apparent good, at least for people in the Western world. The value of the mast-cell-IgE-reaction, for most of us, is historical – it wages war against large-bodied parasites such as tapeworms and schistosomes. (They are large by comparison with bacteria and viruses, and not easily tackled by other immune cells.) These unpleasant invaders have largely been eliminated in the developed world but are still rife in other countries. For millions of years such parasites were an inevitable part of human life, and this bit of our evolutionary past survives in our immune system.
The complexity of allergic reactions
`Each time the pollen season came around. I would start to get these pains, especially in my knees. I asked my doctor about it but she just looked at me rather oddly and said “take a paracetamol”. I couldn’t be sure it was linked to my hayfever, but the pains always came on just after the sneezing started. One year, it was all worse than usual, and I felt very tired too. My face was all puffy and I could feel that something was seriously amiss. That, as I now know, was because my kidneys were being affected. It was years before the doctor would refer me to an allergist, and I actually got an explanation for all this. I think for a long time my doctor thought I was making it up, or just imagining the pain in my knees.’
Karen suffers from a rare complication of hayfever involving an overload of pollen antigens and antibodies in the blood. Very large numbers of both are involved, and are bound to each other in dense tangled masses called immune complexes. Because these are carried around in the blood they are known as circulating immune complexes. They may be too large to be cleared quickly by the normal junk-munching systems that keep the blood clean.
Like a river choked with fallen leaves, which deposits some of the debris on its banks as it flows past, the blood inevitably
The other antibodies
Other than IgE, four main types of antibody exist – IgA, IgD, IgG and IgM. Although some of these antibodies help fight bacterial and viral diseases, they lack IgE’s ability to tackle certain large parasites. These other antibodies do not generally bind to mast cells, and therefore do not cause IgEstyle allergy. But they can be involved in various other sensitivity reactions – it is IgG antibodies that are active in coeliac disease for example, and IgA in dermatitis herpetiformis. And any kind of antibody can participate in circulating immune complexes, causing multiple symptoms (see below).
leaves behind some of the circulating immune complexes. They mostly become deposited in the tiny blood vessels called capillaries, particularly those in the skin, the kidneys and the joints. Inflammation (140) here can cause a range of symptoms.
This problem is known to doctors either as serum sickness or as Type III hypersensitivity. It is a well-known feature of several infections and of some autoimmune diseases.
Unfortunately, the potential for Type III hypersensitivity in allergies such as hayfever is much less well known among doctors, as Karen discovered. As well as affecting hayfever sufferers, Type III hypersensitivity can also be a complication of reactions to penicillin and certain other allergic reactions, such as insect-sting allergy.
When a reaction occurs to snake anti-venom – and it only occurs in an individual who has received snake anti-venom before – this too is Type III hypersensitivity. The snake anti-venom is cultured in horses, and the snake-bitten human who has received the snake anti-venom previously mounts a massive immune reaction to the horse proteins when snake anti-venom is injected for a second time. Large and numerous circulating immune complexes are formed, and although IgE is not involved, a very severe anaphylactoid reaction (see box on p. 59) follows.
Circulating immune complexes do not affect most allergy sufferers. But there are other immune responses that follow on from the initial allergic response in everyone with allergies –they are generally summed up as the ‘Late Phase Reaction’. This reaction starts 4-12 hours after the exposure to the allergen, and lasts about a day. It involves a number of different immune cells (including eosinophils – p. 19) and an even more varied array of messenger chemicals, making everything very complicated for medical researchers to investigate. When allergic symptoms become entrenched and difficult to treat, the Late Phase Reaction is usually implicated. But it has not been given much attention by doctors until recently, because the details are so complex and so poorly understood.

What is Allergy?
Words matter, particularly in medicine. Using the same words to mean different things is a major difficulty for patients when discussing allergies with a doctor. Unfortunately, few patients realise this, and doctors are frequently too busy to explain what they themselves mean. The result can be a great deal of misunderstanding, confusion and mutual irritation.
Unclear meanings can also create problems if you start exploring other treatment options. The word `allergy’ is like one of those cats that eat at six different houses in the neighbourhood: everyone feels as if they own it exclusively. A conventional allergist will understand one thing by ‘allergy’, while a more unorthodox doctor may have a broader definition, and a herbalist or naturopath may be using the word in a completely different way again.
This is an absolute jungle for the medically unqualified, and it can be an expensive jungle if you are looking around for an answer to your health problems. With the help of this book, you should be able to make sense of all this, and understand the seemingly contradictory advice on offer.
The word allergy was coined in 1906 when it was used to mean altered reactivity - any change in the way the body responds to the environment, whether immunity to a disease already encountered, or a sudden fit of sneezing from pollen. Immunity to disease was soon shunted off into a separate category
altogether, leaving allergy with a narrower meaning:
any adverse reaction to substances that are normally harmless - definition 1. In this book, that meaning is covered by the word sensitivity.
One group of American doctors, who later became known as clinical ecologists, stuck with this definition. Their broad view of allergy is still found among some other doctors today, generally those whose approach to medicine is fairly unorthodox. It is a concept of allergy that is also shared by most practitioners of alternative medicine or complementary therapists.
The rift between the clinical ecologists and mainstream medicine came in the 1920s when the definition of allergy used by conventional doctors was narrowed further to mean reactions to harmless items where the immune system is definitely involved -definition 2. The term immune sensitivity is used in this book to convey that meaning.
In the 1960s, conventional allergists narrowed the definition of allergy again. It was an exciting time because the antibody known as IgE (sometimes called the allergy antibody - see box on p. 12) had just been discovered. The new, tighter meaning of allergy was
reactions to harmless items where IgE is involved -definition 3.
If asked to define allergy, most doctors would give the second of these definitions.
However, when they talk of ‘a tendency to allergy’, ‘allergy treatment’ or `the allergy epidemic’, doctors are generally using the third definition, and just mean IgE-mediated allergy. They may not be conscious of the fact that they are switching from one definition to another. This is not an ideal situation but, generally speaking, it does not create too many problems.
This book deals with ‘allergy’ in the very broadest sense of the word - all kinds of sensitivity. However -and this is purely for the purposes of clarity - where the word allergy is used in the text it always means IgE-mediated allergy (definition 3).
Other immune-mediated problems are called non-IgE immune sensitivity in this book.
Finally, any reaction where the immune system has no proven central role is called an intolerance. (As for other technical words, if you want to find the full definition, look in the index and turn to the page number shown in bold type.)
If you are reading widely on this topic, you may come across sensitivity used either according to definition 1 above, or as another name for intolerance. You may also encounter the word hypersensitivity. This is actually a precise medical term,
but be warned that some writers use ‘hypersensitivity’ very loosely to mean just ’sensitivity’ (definition 1).
Remember that medical politics and economics are powerful forces in all this debate over meanings. Words are quite often redefined by medical interest
groups (such as professional associations) with the clear intention of staking out territory and claiming sole access to medical truth. What is at stake, ultimately, is the right of different doctors to treat patients with certain conditions - and the right of patients to choose for themselves. To add to the longstanding battle over ‘allergy’, there are now rival claims about the meaning of intolerance (74) which have distinctly political overtones.
When you talk with doctors, using the most appropriate terms will help enormously. Talking to a mainstream doctor about ‘food allergy’ when the symptoms suggest food intolerance, for example, is very likely to cause annoyance. This is not unreasonable because IgE-mediated food allergy, unlike food intolerance, is a disease that can very suddenly kill an otherwise healthy person. Using the term `food allergy’ for a headache or mild bowel symptoms is, doctors feel, trivialising a potentially fatal condition.
The important thing is to get along well and communicate clearly with doctors, not to get into a battle about what words mean (in that sense, words don’t matter - they are just labels). Avoid using the word ‘allergy’ unless you are sure it fits in with your doctor’s perception of what is wrong. Just describing how you react - the actual symptoms - is usually the best approach. If you need a general word for your condition, ’sensitive’ is usually a much more diplomatic choice than ‘allergic’.