An immune response to a harmless substance. The machinery involved evolved to deal with parasites, the response causes the disease rather than the substance doing so, and allergy has become substantially more common in developed countries within a few generations.
Allergy in the classical sense is mediated by immunoglobulin E, one of the antibody classes described in the antibodies capsule.
On first exposure, the immune system produces IgE against the substance, and that IgE binds to mast cells in tissue and basophils in blood. Nothing is felt; the person is now sensitised.
On subsequent exposure, the allergen cross-links the bound IgE, which triggers the mast cell to release its granules within seconds. Histamine is the principal mediator, and it dilates blood vessels, increases their permeability, contracts smooth muscle and stimulates nerve endings.
The symptoms follow directly from those actions. Leaking vessels produce swelling and hives; smooth muscle contraction in the airways produces wheeze; nerve stimulation produces itch.
A second, later phase follows over hours as other immune cells are recruited, which is why symptoms can persist after the allergen is removed.
An allergen is generally a protein, and the substances involved are unremarkable: pollen, dust mite, animal dander, particular foods, insect venom and some drugs.
Allergic rhinitis, or hay fever, is triggered by airborne allergens and affects nasal and eye membranes.
Asthma involves airway inflammation and reversible narrowing, and is frequently but not always allergic in origin.
Atopic dermatitis, or eczema, involves an impaired skin barrier and inflammation, and its relationship to allergy is more complex than a simple response to contact.
Food allergy affects a small percentage of the population and is more common in children, with several forms commonly outgrown.
Anaphylaxis is the systemic form and is a medical emergency. Widespread mediator release causes blood vessels to dilate throughout the body, blood pressure to fall and airways to constrict. Adrenaline is the treatment, and it works by reversing exactly those effects.
Contact dermatitis, as with nickel or poison ivy, is a different mechanism, mediated by T cells rather than IgE, and develops over a day or two rather than within minutes.
Intolerances, including lactose intolerance, are not allergies at all. They involve digestion rather than immunity, and the distinction matters clinically because the risks and the management differ entirely.
The IgE system appears designed for parasites, particularly helminth worms, and the responses it produces make sense against them: mucus secretion, smooth muscle contraction and itching all tend to expel or dislodge a parasite.
Allergy is that machinery directed at a target it should ignore.
The response is not merely useless but harmful, since the damage is caused entirely by the immune reaction rather than by the substance, which is inert. Pollen does nothing to a person who is not allergic to it.
Allergic conditions have become substantially more common in developed countries over recent decades, and the increase is too rapid to be genetic.
The hygiene hypothesis, treated in its own capsule, proposed that reduced exposure to infections in early childhood leaves the immune system inadequately calibrated. It has been substantially revised, since the correlation is with microbial exposure generally rather than with infections, and the original formulation does not fit the data well.
The old friends hypothesis is the current refinement, holding that reduced exposure to the microorganisms humans co-evolved with, particularly environmental and gut organisms, is the relevant change rather than reduced illness.
Other candidates include dietary change, vitamin D status, antibiotic use altering the gut microbiome, air pollution, and reduced skin barrier integrity from soaps and detergents.
The evidence supports several contributing factors and no single explanation, and the honest position is that the increase is well documented and its cause is not established.
Testing identifies sensitisation, meaning the presence of specific IgE, which is not the same as allergy. Many people test positive to substances they tolerate without symptoms, so tests must be interpreted alongside history rather than alone.
Avoidance remains the primary management for established allergy.
Antihistamines block histamine receptors and control mild symptoms. Corticosteroids reduce the inflammatory phase. Adrenaline is the only treatment for anaphylaxis and delay in giving it is the main determinant of poor outcomes.
Immunotherapy administers gradually increasing doses to induce tolerance, and is effective for venom and several airborne allergens.
Prevention advice reversed substantially. Guidance for decades recommended delaying introduction of allergenic foods to infants. The LEAP trial, published in 2015, found that early introduction of peanut in high-risk infants reduced peanut allergy by a large margin, and guidelines were changed accordingly. It is a clear case of a plausible precaution having the opposite of its intended effect.
Allergy affects a substantial and growing share of the population, and asthma alone is among the most common chronic conditions worldwide.
It is also the clearest everyday demonstration that the immune system's errors are as consequential as its successes, since the entire disease is produced by a defence mounted against something that was never a threat.
