Science of Allergy

The immune system protects us against microbes and other invaders and helps to repair tissues if they are damaged. The immune system is made up of a number of organs, cells and substances (e.g. antibodies) which it uses to help it carry out these functions. Each of these components has their own unique role to play. For example, cells which are called neutrophils eat and kill microbes, other types of cells called eosinophils use poisons to kill worms and parasites, while others known as T cells fight viruses by killing cells of the body in which the viruses are living. T cells also work by helping all of the other cells of the immune system do their job more effectively. In order for the cells of the immune system to work efficiently, they must be able to get to the area where the microbe is present or where the tissue has become damaged, as quickly as possible.

Cells of the immune system travel around the body mainly in blood vessels and they must be able to leave these blood vessels quickly and travel to where they are needed. (Figure 1.) This process is called inflammation.

Figure 1. Cells of the immune system leave the blood vessel and are guided to the site of infection or injury by chemicals. This process is called inflammation.

Interestingly, it is when cells of the immune system begin to leave the blood vessels that we experience several common symptoms such as fever, loss of appetite, increased secretions (e.g. runny nose), cough, sneezing, swelling and pain in the injured/infected tissues. For example, if we have an infected throat, cells of the immune system travel to this site and our throat becomes swollen painful and sore. We may also have a fever, be tired and not feel like eating. Many of these symptoms occur because of the chemicals (Figure 1) which are produced by cells and other sources which warn the immune system that an invader is present or that a tissue has become damaged. Although these symptoms are unpleasant when we experience them we can be reassured that our immune system is working overtime. One cell which produces these chemicals which warn the immune system that an invader is present is known as a mast cell. One of the chemicals it produces is called histamine link which helps cells of the immune system (especially eosinophils) get to the precise place in the body where the intruder is present.

Earlier we mentioned that antibodies are an important part of the immune system. The main role of antibodies in the immune system is to help neutrophils eat microbes, in much the same way as we use a fork to help us eat our food. Antibodies have other roles too, and they can help mast cells (above) recognise when an invader is present and cause them to secrete the chemicals which guide cells of the immune system to the site of infection. It is worth noting, that the immune system is very destructive and it is very important that this destructiveness remains firmly focused on the microbes and other invaders which are present everywhere in our environment.

Occasionally instead of the immune system reacting to invaders or to tissue damage, it reacts with otherwise harmless substances in the environment such as pollens, metals or most commonly the excretions of a very common bug known as the house dust mite. When this arises we call it “allergy” and the harmless agents in the environment to which the immune system has responded, we call “allergens”. Allergy can be defined as an inappropriate or exaggerated immune response to harmless substances (allergens) in the environment. As a result of this abnormal response the person develops typical signs and symptoms of allergy such as a runny nose, itchy eyes, wheezing or a skin rash (Figure 2). Usually, these symptoms are mild and readily controlled. However, in a tiny minority of patients they may develop a severe allergic reaction termed “anaphylaxis”

Figure 2. The red and itchy eye typical of hay fever is illustrated in this patient allergic to tree pollen .

Most allergy symptoms, like the symptoms which occur when the immune system is working normally, happen when cells of the immune system are leaving the blood vessels and travelling through the tissue, a process which we previously termed inflammation.

There are a number of distinct ways in which the immune system may respond to allergens and cause symptoms. Most commonly, a patient suffering from allergy makes a particular type of antibody known as an IgE (pronounced literally I, g, e) antibody to the allergens in question.

IgE antibodies are a particular type of antibody that is normally used to protect us against parasites such as worms and flukes. The IgE antibodies particularly work in conjunction with other cells of the immune system such as mast cells and eosinophils to help get rid of the worm or fluke by poisoning it. (figure 3). During this normal process, a patient may experience symptoms such as swellings, itchy rashes, hives, wheezing, the production of excessive secretions and diarrhoea. These symptoms are part of inflammation and are caused by activation of the immune system. Very occasionally as a result of this immune response a patient may experience collapse, especially if the worm or parasite gets into the blood stream. Often however, when the eosinophil arrives at the worm it realises that the job is too big to handle by itself and it sends out yet other chemicals to attract additional types of cells such as macrophages (the real “heavyweights” of the immune system), T cells and natural killer cells. All of this means more inflammation, more symptoms and the potential for additional collateral damage as the immune system attempts to remove the invader.

In the most common type of allergy which is caused by IgE antibodies, the patient makes IgE antibodies not against worms and other parasites but against the harmless agents in the environment which we have termed allergens. These antibodies work in exactly the same way as shown in figure 3 but instead of being directed against the worm they are directed against the allergens (pollens etc) in the environment

(figure 4.)

The IgE antibodies now are working in conjunction with the mast cells and eosinophils to try and get rid of the allergen. This process gives rise to the symptoms of allergy, which are similar to the symptoms which may arise during infection with parasites. The features of allergy which are experienced, will partly depend on the part of the body in which the immune system encounters the allergen. If it is in the eyes and nose, the symptoms will be mainly of hay fever (sneezing, itchy eyes and runny nose). link If however, the allergen is encountered lower down in the respiratory system the symptoms will be mainly wheezing and asthma link. Sometimes a patient would have symptoms of both hay fever and asthma and a skin rash known as eczema. link Less commonly a patient may become allergic to a food and in this instance the allergen is encountered in the gastrointestinal tract and sometimes in the blood stream link. When this happens the symptoms would be mainly of nausea, diarrhoea and very rarely collapse. Insect venom, animal danders (especially from house pets) and a whole variety of drugs may also be targeted in some patients with IgE related allergy links. As drugs and insect venom are ingested or injected they often get into the blood stream and some individuals may experience severe allergic reactions when exposed to these allergens.

A person with IgE allergy may make IgE antibodies to only one allergen. However, it is quite common for a person to make IgE antibodies against several different allergens. Such a person may therefore experience symptoms of allergy after contact with each of these allergens. IgE allergy frequently runs in families. It is interesting, that IgE allergy is very common in the western world where there are few parasites but it is uncommon in the underdeveloped world where it seems that the immune system is too busy with parasites to be bothered with allergens. There is also some evidence that this type of allergy is less common in children who are breast fed. Another interesting feature is that we tend to “grow out of ” IgE allergy as we get older. The reasons for this are not very clear but may well be due to hormonal influences. A particular feature of IgE allergy is that a person usually develops symptoms of allergy within minutes of exposure to the allergen. link

As other diseases especially infection may mimic allergy, a careful documentation of the patient’s history can often identify if the person is likely to be suffering from allergy and what it is they are allergic to. For example, a person may only have symptoms of hay fever during May to September indicating that they are likely to have pollen allergy. A variety of tests are also available to aid in the diagnoses of allergy.

As discussed earlier in IgE allergy, symptoms of allergy arise within minutes of exposure to allergens. The skin can therefore be pricked with a number of suspect allergens and examined for signs of inflammation after approximately fifteen minutes. (Figure 5) This is known as a skin prick test link and can be a useful aid to the diagnosis of allergy. Blood tests are also frequently used to aid in the diagnosis of allergy. The total amount of IgE antibody can be measured in blood and it can also be determined what allergens the IgE is directed against (specific IgE). The number of eosinophils can also be measured in blood and individuals with allergy often have increased numbers of these cells. However, a diagnosis of allergy requires both a careful history and physical examination and a detailed consideration of the results of skin and blood tests. Unfortunately, there are occasional patients in whom, despite testing, it remains difficult to be certain of the precise cause of the allergic reaction. It is important to note, there is no magic wand or machine that can be waived over a patient to detect or diagnose allergy.

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Figure 5. The skin is pricked with a small amount of allergen and examined for signs of inflammation. Typical redness and swelling are observed after approximately ten minutes .

Treatment of IgE allergy.

An important aim of treatment is to identify the allergen which is causing the problem and to avoid or minimise contact with it. In some cases, total avoidance is possible, e.g. in food or drug allergy, in other situations contact can be lessened e.g. regular use of the vacuum cleaner in individuals with house dust mite allergy. However, in many cases avoiding complete contact with the allergen is not possible and drug therapy may be required. The most common form of treatment is antihistamine drugs (links). These neutralise the histamine released from mast cells (figure 4.) which results in attraction of eosinophils to the site of allergen exposure. Another drug called sodium chromoglycate helps prevent the mast cell from releasing histamine in the first instance. Both of these types of drugs are very safe and the only side effects are likely to be drowsiness in some individuals treated with some of the older anti-histamine drugs. Usually these drugs adequately control the symptoms of allergy. However, in some conditions especially asthma, other cells of the immune system such as macrophages and T cells (see above) become involved in the allergic reaction and other more potent anti-inflammatory drugs such as hydrocortisone (link) are prescribed (note; there are several types of hydrocortisone like drugs). In most patients with asthma very small doses of this drug can be delivered to the site of the allergic reaction (i.e. the lungs) by using inhalers. This greatly minimises drug exposure while effectively controlling symptoms. In a very small number of individuals with a history of severe allergic reactions, they may need to be treated with a drug called adrenaline. This drug neutralises the effects of the chemicals released from mast cells and other sources and are an effective way of reversing severe allergic reactions. This drug is normally carried in a convenient form (link) by highly sensitive patients. It can then be immediately administered in the event of a severe allergic reaction.

T cell allergy .

Another form of allergy may be observed if a different cell of the immune system known as a T cell responds inappropriately to an allergen. This type of allergy most commonly arises through contact of the skin with metals, chemicals and detergents etc. The main symptom of this type of allergy is a skin rash, in the area of skin in contact with the allergen (Figure 6).

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Figure 6. Examples of T cell allergy. A, the patient is allergic to eye shadow, B the allergy is to hair dye and C the allergy is to the metal in the trouser zip. Note that the allergy only occurs on the skin in contact with the allergen.

Sometimes this type of allergy is called “contact sensitivity” or “delayed hypersensitivity”. Unlike IgE allergy this allergic reaction usually arises approximately 2-3 days after contact with the allergen.

What is thought to happen in T cell allergy is that the allergen (cosmetic, detergent, metal etc) mixes with the skin and alters some of the cells and molecules which make up normal skin. When this occurs, the T cells confuse the altered skin with an invader and start reacting with it. In the process the T cells attract macrophages (Figure 7) to the site and it is this which causes most of the inflammation and damage to the skin. This type of allergy never causes severe reactions and the symptoms are confined solely to the skin or mucous membrane areas.

Diagnosis of T cell allergy link.

T cell allergy is best diagnosed by doing what is called a Patch Test link. This involves placing a small amount of the suspected allergen on the skin, covering it with a light dressing and observing for signs of inflammation after 2-3 days ( Figure 8).

Figure 8. Patch test Inflammation can be observed in the skin after 48Hrs contact with the allergen.

Treatment of T cell allergy.

As with IgE allergy the best form of treatment is to avoid contact with the allergen. This is usually more straightforward than with IgE mediated allergy. For example the offending cosmetic can be avoided or if the problem is in the hands gloves can be worn to protect them. For the alleviation of a severe skin reaction hydrocortisone creams may be prescribed for a short period.

Allergy caused by other antibodies. (IgG allergy)

There are different types of antibodies that the immune system uses to repel invaders. We mentioned earlier that antibodies work like forks in helping immune cells eat microbes. Using this analogy, different types of foods sometimes require the use of different sizes and types of forks. We noted earlier that IgE antibodies help trigger mast cells. Different types of antibodies such as IgG can help and trigger cells such as neutrophils, natural killer cells, macrophages and in addition can help activate a series of chemicals in the blood known as complement. Complement (like histamine) helps get cells of the immune system to site of invasion or tissue damage. IgG is the most important type of antibody that our immune system uses to get rid of infections and if we don’t make enough of this antibody we will suffer from excessive infections. Interestingly, when we are born our immune system is not able to make any antibodies and it doesn’t start producing them until the first or second year of life. During pregnancy, a mother makes lots of IgG and transfers it to the developing child before birth. In this way the child is born with large amounts of IgG which it uses to defend itself against infection.

In IgG allergy the immune system makes IgG antibodies inappropriately to allergens. When the IgG antibodies bind to the allergens they can activate complement and cells of the immune system and cause the symptoms of this type of allergy (Figure 9).

Figure 9: IgG recognises allergen. Complement damages tissue and attract neutrophils which cause further tissue damage.

This is probably a much rarer form of allergy than IgE or T cell allergy. It is most likely to happen when a susceptible person is exposed to certain drugs or inhales certain types of moulds. If this type of allergy is caused by a drug the most likely symptoms will be aches and pains in the muscles and joints, skin rashes or hives and stomach upsets. A patient may make IgG antibodies against allergens which are inhaled and these allergen are usually moulds, yeasts or dusts from caged birds. This may give rise to a cough or to wheezing and the resulting allergic diseases have names such “farmers lung” “pigeon fanciers disease” etc. Unlike IgE allergy or T cell allergy it is often difficult to directly relate the development of symptoms to contact with allergen.

Diagnosis of IgG allergy is based on history, physical examination lung function tests and X-rays. In the case of drugs which may cause this type of allergy withdrawal of the offending drug will result in disappearance of the symptoms of allergy. There are blood tests available for diagnosing IgG allergy but they are not as useful as in IgE allergy. In general, treatment will be aimed at avoiding contact with the allergen and may also necessitate the use of hydrocortisone.