This is the role of our immune system. As there are many types of aggressors (which in medical terms are called antigens), the immune system has developed complex and sophisticated ways to fight them. One defending strategy is to produce antibodies. These are small protein molecules in the shape of the letter Y, designed to recognize specifically each foreign substance and microbe that comes in contact with our body. Upon this recognition, the antibody sticks to the aggressor preventing it from exerting its harmful actions and at the same time helping the immune cells to destroy and eliminate it.

Most of the time, the actions of the immune system are beneficial. In the absence of the immune system our body would disintegrate under the attack of aggressive chemicals and microbes from the environment. 

But sometimes the immune system gets things wrong and treats as aggressors substances which possess no real threat for us. In the absence of a real aggressor, the defending attack mounted by the immune system only results in harming our body.Allergy is one example of such over-reaction in which the immune system wrongly identifies as harmful harmless substances such as pollen, house dust mites or even food.  A whole defending strategy is then mounted.

The mast cell
The first time when we come in contact with the allergen, the immune system  will produce special antibodies that can recognise the allergen.  These are called immunoglobulin E (IgE) . These antibodies then attach to a special cell present in the lining of the nose, lungs, eyes, stomach, gut and skin – the mast cell. When the allergen is encountered again, IgE binds them and sends awake-up message to the mast cell which then burst with the release of chemicalsubstances that are called mediators.  The commonest of these is called histamine and it will cause symptoms like itching, sneezing, redness, nasal dripping or lacrimation. This is why anti-histamine drugs are often helpful. 

The eosinophil
Next the immune system sends into battle a contingent of different cells called eosinophils, which also contain mediators, only that much more aggressive than those of the mast cells.

These mediators are released from the eosinophils in an effort to stop the harmful invasion. But as there is no harmful invasion, they cause symptoms or even tissue damage instead.  In hay fever for example, the immune system thinks that the pollen grains in the air we inhale are a threat. Consequently IgE antibodies are produced which on re-exposure to pollen triggers the release of histamine from the mast cells causing symptoms like sneezing, nose and eyes itching and redness, nasal dripping. Eosinophils also come and release their mediators. This causes severe nasal blockage and also worsens all the symptoms mentioned above. 

The substances that can cause an allergic reactions are called allergens  There are many allergens (pollen, house dust mite, feathers, moulds, cat dander, foods) and they can all trigger this type of allergic response.  The immune system reacts in essentially the same way to any of them but the same reaction can cause a variety of diseases and symptoms, depending on which organ is affected  (hay fever in the nose, asthma in the lungs, urticaria in the skin). The intensity of the reaction can be quite different each time, even in the same person. But thanks to immune system memory, every time the same antigen attacks the body again, the immune system recognises it in a fraction of the time and sets the response within a few hours.

This is why someone suffering from hay fever might have come in contact with the allergen several times without having any symptoms. However, once that the pollen allergen has been memorised by the immune system and the ways to defend the body against it have been set, the person will react promptly, every time when coming in contact with it.

What is sensitisation?

If you had a skin or blood allergy test which was positive (the dust mite for example) the doctor or nurse might  have told you that you are sensitised to this allergen. What does the word sensitisation mean? Is it synonymous with allergy?  

Being sensitised means that the immune system is already acquainted with the allergen (that is it came in contact with it, has synthesised IgE antibodies against it, and has committed it to its memory, so it could launch a defence reaction when the allergen reappears).  The time it takes to become sensitised to an allergen varies from person to person, from a few days to several years.  Sensitisation occurs silently, without one knowing that it happened. This is because unless IgE antibodies trigger release of histamine from the mast cells, sensitised persons will have no symptoms.  

Sensitisation is the first step towards developing allergy but allergy does not always follow.  Some people stop in this phase and never develop allergy symptoms even if exposed heavily and persistently.  These people have positive allergy tests but no manifestations of allergy. Therefore they are considered to be healthy but with a higher risk for developing allergy than people wothout sensitisation.

So if you had a positive test, but no symptoms of allergy  you don’t have to change anything in your life. Remember that allergy skin tests and blood tests assess whether you have IgE against a particular allergen. This is not a cause for concern and so don’t go out of your way to try avoiding that allergen. Allergen avoidance measures are often difficult to follow; think what it would mean to avoid all foods containing soya for example!. There is also recent evidence to suggest that rather than preventing you from getting the allergy, allergen avoidance, followed by accidental re-exposure, could actually cause the allergy to start. 

So remember
You can be sensitised without being allergic, but you can’t be allergic without being sensitised!

How does atopy differ from allergy?

Very often allergy sufferers are said to suffer from atopy and are described as atopic.  So what does this means; is it the same thing as allergy?  The answer is not straightforward. 

Atopy is the genetic predisposition of an individual to produce high quantities of IgE antibodies in response to allergens in the environment (pollens, house dust mites, moulds, cat dander, foods, etc).  Heredity is very important: the an abnormal inclination of the immune system to react to allergens is inherited from the mother, the father, or maybe both. 

So atopy is a innate state which is silent (a child born atopic does not differ in any way from a non-atopic child). Atopy precedes and allows sensitisation to take place. Currently there is no test for atopy (this is because we don’t know yet all genes responsible for allergy and also we dn’t have genetic tests to identify those we know).  However, a person can suspect that they might be atopic if they have family relatives with allergy.  We can only identify the atopic state when it progresses to sensitisation (when the person has developed IgE which will give a positive skin or blood allergy test).  

So these are three states of allergy:

Atopy
The inherited condition that predisposes a person to allergy

Sensitisation
Atopy taken one step further – the immune system is primed (specific IgE has been formed) to react to an allergen

Allergy
Sensitisation taken one step further – symptoms occur following contact with the allergen

So you need to be atopic to become allergic but not all atopic people become allergic.  So what is it that makes atopic people behave differently and progress to allergy.

Environmental factors can certainly influence the development of allergy.  For example, someone with inherited atopy might become sensitised to hamsters because of an early exposure to them.  But if that person does not subsequently come into contact with hamsters, no allergy will develop. However things are further complicated by the fact that several genes create the predisposition and several environmental factors can interact with these.  In the past twenty years several genes involved in allergy have been discovered and many lifestyle pro-allergenic factors identified (and more are are constantly disclosed). 

This is just the start of an understanding about how genes and environment factors interact to result in allergy. These interactions are complex and unfortunately there is no single answer for all allergy sufferers.  It will take some time before we will understand properly what makes us allergic.

Other forms of allergy

The mechanisms of allergy described above is mainly involved in hay fever, eye allergy, asthma, insect allergy and simple food allergy. Skin allergy, drug allergy and other type of food allergy can work in rather different ways.  

Allergy in the skin involves rather different mechanisms.  Atopic (allergic) eczema is the usual type of eczema that starts in childhood.  IgE antibodies are certainly involved in causing and maintaining the condition, but infection, other immune mechanisms, and inherited abnormailities in skin structure can also be involved.

Contact dermatitis (sometime called contact eczema) is another common skin condition linked to allergy; the responsible allergens being chemical substances that come into contact with the skin.  Amongst the commonest contact allergens are compounds containing the metals nickel or chrome, but many other substances such as fragrances, synthetic dyes, animal products, food products and cosmetics can be to blame.  In this case the allergy is of a different type sometimes called cell-mediated allergy because sensitised white blood cells rather than IgE antibodies are at the heart of this kind of reaction.

Allergy in the gastrointestinal tract can also behave rather differently. Coeliac disease (its other name is gluten enteropathy) is the name given to a gut condition caused by allergy to a protein called gluten that is found in wheat, rye and barley.  Although an immune system reaction is involved, it works in quite a different way (IgE antibodies are not involved) and this means that the symptoms (tiredness, diarrhoea, iron-deficiency anaemia) are very different from those normally associated with allergy.  It is an example of non-IgE-mediated allergy.

What is food intolerance?

Simple (antibody-mediated) allergy to foods such as fish, shell fish, nuts, fruits, wheat and egg affect up to 4% of adults and 8% of children. These reactions may result in swelling and or itching of the mouth, difficult breathing, tummy pain, vomiting, diarrhoea or even loss of consciousness usually within minutes from eating the food.  However, many genuine food reations are not caused by this easily-diagnosed form of food allergy.  Around 1 person in 6 finds that they get symptoms each time they consume a certain food, and therefore benefit from its avoidance even though allergy tests are negative.  Such cases are usually described as food intolerance although it is clear that there are a number of different kinds that are caused in a variety of different ways.   

False allergy 
The scientific term is pseudo-allergy, pseudo meaning false in Greek
This causes similar symptoms to allergy (e.g.  skin rash, itching, sneezing, runny nose, coughing, wheezing).  The difference from a real allergy is that false allergy is not caused by a recognised dysfunction of the immune system, and no specific IgE antibodies can be found.  This means that if allergy tests are performed, they will be negative.   

False allergy can occur in both atopic (people without the allergic tendency and with no family history of allergy) and non-atopic people.  Certain drugs (for example aspirin and aspirin-like drugs such as ibuprofen) can cause side effects that mimic true allergy by interfering with the body’s normal biochemical processes.  Some foods (e.g. strawberries, wines, chocolate, fish that is not fresh) contain enough histamine and similar compounds to cause susceptible people – those that metabolise these compounds inefficiently – to develop false allergy if they eat enough of them.

Enzyme deficiency 
The gastrointestinal tract produces a variety of digestive enzymes to assist us in digesting our food.  Some people to suffer symptoms when they eat certain foods because they lack the necessary enzyme required to digest it.  

The commonest example is lactose intolerance, an inability to digest the sugar lactose that is present in milk and milk products.  This enzyme is called lactase and lactase deficiency is very common, especially amongst Asian people.  Lactose intolerance is considerably under-diagnosed.  

There are also a number of less common conditions that are due to deficiencies of other enzymes.  

Food sensitivity 
The scientific term is non-allergic food hypersensitivity 
Studies that have used elimination diets followed by 'blinded' re-introductions of the avoided foods has shown non-allergic food sensitivity to be reproducible and therefore not all in the mind. However, this type of food sensitivity is far from easy to diagnose and may have been considerably underestimated as a provoking factor in a number of conditions not conventionally thought of as due to allergy.  Indeed, most of these are conditions have no generally accepted cause.  

Irritable bowel syndrome is a good example of this. Studies have suggested that food sensitivity may be involved in about a half of all cases but his is a controversial idea that is not generally accepted. However, this debate is likely to continue because of two findings from recent studies. A hidden type of true allergy in which the allergic reaction is localised to the lining of the gut (and therefore does not show up on allergy tests) may explain some cases whilst cell-mediated (rather than antibody-mediated) food allergy may explain other cases.  Cell-mediated food allergy may also be the explanation when foods provoke eczema in children and food allergy tests are negative.   

So it is possible that future research may unfold a much wider role for food allergy in its various forms.  Already there have been scientific studies that have suggested that food sensitivity with negative allergy tests may trigger or worsen the symptoms of the following common conditions. 

 
Whilst it is very clear that much more work needs to be done in this very important area of medical research (and, sadly, little is being done at present), in at least the above conditions it is worth considering the possibility of food sensitivity.  Whilst the possibility of following a trial elimination diet under the supervision of a doctor or dietitian might seem appealing, this will certainly not be suitable in all cases and patients certainly need to take into account, and be guided by the advice and experience of health professionals.     

As with any medical treatment, side effects are possible with the elimination diet approach.  Because as yet there are no accurate and trusted tests, some assessment needs to follow the 'trial and error' approach making it imperative that patients follow professional guidance.  Whilst in the majority of cases, this approach is safe and satisfactory, in a few cases problems may arise.  For example, some patients may be very vulnerable and susceptible to suggestion.

In such cases, pre-existing anxiety and depression can be worsened by providing patients with a fresh focus for their fears and anxieties.  In the past, certain cases, undoubtedly suffering more than a small element of psychiatric illness and anorexia in addition to any 'allergies', have gained media attention, with headlines containing emotive phrases such as 'Allergic to the Twentieth Century'.  

Psychological effects

When medical scientists are investigating see if food intolerance might be the explanation for uneplained symptoms they need to take psychological factors into account.  When people suffer from symptoms that are unexplained, they are often considered to be suffering from anxiety or depression.  Quite often these patients are keen to find alternative explanations for their symptoms and this can make them prone to suggestion.  One type of anxiety is called  phobia - an irrational fear of harmless things.  So for some patients a suspicion of food intolerance could turn out to be a food phobia.  We also know from animal experiments that sympoms indistinguishable from those of allergy can be induced by psychological conditioning.

The name for symptoms induced by suggestion is placebo effect and the best way to exclude this is to use a double-blind test.  An explanation of both these terms follows.  

Placebo effect 
This is the name of the benefit that is due to belief in the doctor or belief in the treatment as opposed to a real or treatment effect.   When doctors are trying to assess treatments objectively, as in a clinical trial, the reason they do not usually compare treatment with no treatment is because of the existence of placebo effect which in many cases can be very significant.  All kinds of treatment for example conventional medicines, herbal medicines, physiotherapy and even elimination diets can cause placebo effect.  So doctors prefer to compare treatment with placebo treatment.  This might be a dummy pill (in the case of conventional or herbal medicine); a safe but ineffective physical treatment (in the case of a study of physiotherapy); or a diet comprising non-suspect foods (in the case of a study of an elimination diet).  

Double-blind test

A double-blind test

A double-blind test sticks to two principles.  Firstly things are so arranged that the patient has no idea whether real or placebo treatment is being used.  Secondly things are so arranged that the doctor or nurse reviewing the patient also has no idea whether real or dummy treatment is being used.  So it becomes doubly difficult for psychological effects to have any bearing on the result.  So if a difference between treatments is still shown when a double-blind test is used, this difference must be due to treatment effect rather than placebo effect.