What Is an Allergy? An Immune Response to Something Harmless

The classic immediate allergic reaction runs on a specific antibody class, immunoglobulin E, which exists primarily to deal with parasitic worms. On first exposure to an allergen, an unlucky combination of signals leads the immune system to produce immunoglobulin E against it rather than ignoring it, a process called sensitisation, which produces no symptoms at all. Those antibodies then attach to mast cells in tissues and basophils in blood, arming them. On a later exposure, the allergen binds and cross-links those antibodies, and the mast cell degranulates, releasing histamine and other mediators within seconds to minutes. The effects follow directly from what those mediators do: blood vessels widen and leak, producing swelling, redness and a drop in blood pressure; smooth muscle contracts, narrowing airways; mucus production rises; and nerve endings are irritated, producing itching and sneezing. A later phase hours afterwards brings other immune cells in and causes the prolonged inflammation seen in asthma and eczema.

The word is used for a range of reactions with different mechanisms and different implications:

• •True immunoglobulin E mediated allergy, which is fast, reproducible, potentially life threatening and testable
• •Food intolerance, such as lactose intolerance, which is an enzyme deficiency causing digestive symptoms and involves no immune response at all
• •Coeliac disease, which is an immune condition and a different one, being an autoimmune reaction to gluten that damages the intestinal lining rather than an immediate allergy
• •Non-allergic hypersensitivity to drugs, where a substance triggers mast cells directly without antibodies, producing similar symptoms without sensitisation
• •Contact dermatitis, which is a delayed T cell mediated reaction appearing a day or two after exposure to nickel, fragrances or plants, not an immediate one
• •Anaphylaxis, the systemic severe form, which involves multiple organ systems, can kill within minutes and is treated with adrenaline into the thigh muscle, with antihistamines being useless for it

Allergic disease has risen substantially in industrialised countries over several decades, faster than genetics can explain, and the leading explanations concern early environment. The hygiene hypothesis, proposed in 1989 from the observation that hay fever was less common in children with more older siblings, held that reduced early infection leaves the immune system improperly calibrated. It has been substantially revised, since the relevant exposure appears to be not infection but the broader microbial environment, particularly the gut microbiome, whose development is influenced by birth mode, breastfeeding, antibiotics, diet and contact with animals and soil. Farm studies have been influential, repeatedly finding markedly lower allergy rates among children raised on traditional farms, with exposure to cowsheds and unprocessed milk associated with protection. A separate and complementary idea is the dual allergen exposure hypothesis, which proposes that exposure through inflamed skin promotes sensitisation while exposure through the gut promotes tolerance, which fits the strong association between infant eczema and later food allergy.

For years parents were advised to delay introducing peanuts and other allergenic foods to infants, on the reasonable-sounding assumption that avoiding exposure avoids sensitisation. The LEAP trial, published in 2015, tested it directly in infants at high risk and found the opposite: early and regular introduction of peanut from around four to eleven months reduced the development of peanut allergy by roughly eighty percent compared with avoidance. Guidelines across several countries reversed accordingly, and now recommend introducing allergenic foods early rather than late. Treatment has also moved beyond avoidance and rescue medication. Allergen immunotherapy, giving gradually increasing doses by injection or under the tongue over years, can induce lasting tolerance and is established for pollen, dust mite and venom allergy. Oral immunotherapy for food allergy raises the threshold at which a reaction occurs, which protects against accidental exposure without curing the allergy, and carries its own risk of reactions during treatment. Monoclonal antibodies targeting immunoglobulin E itself are now used in severe cases.

An allergy is a correctly executed immune response aimed at a harmless protein, using immunoglobulin E antibodies that arm mast cells during a symptomless first exposure and trigger a rapid release of histamine on a later one. Intolerance, coeliac disease and contact dermatitis are different mechanisms despite similar language. Rising rates are linked to early microbial environment rather than to infection as such, and the 2015 LEAP trial reversed decades of advice by showing early peanut introduction cuts allergy by around eighty percent.