FEATURE ARTICLE
Why We Develop Food Allergies
Coached by breast milk and good bacteria, the immune system strives to learn the difference between food and pathogens before the first morsel crosses our lips
Per Brandtzaeg
Cultivating Tolerance
Oral tolerance is not a single process but a complex series of events that contribute to intestinal and systemic immunosuppression. Many variables influence the development of oral tolerance (and therefore of food allergy): genetics, age, the dose and postnatal timing of fed antigens, the structure and composition of those antigens, the integrity of the epithelial barrier, and the extent to which nearby immune cells are simultaneously activated.
Human milk helps the gut tolerate certain food antigens early in life. Antibodies to gluten peptides from wheat are present in breast milk, and breastfeeding has been shown to protect significantly against the development of gluten-triggered celiac disease in children. This observation hints that mixed feeding, rather than abrupt weaning, may promote greater tolerance to food proteins in general.
This tolerance depends in part on the mothers' own immune function. In a study of breastfed infants, the ones whose mothers had low levels of anti-bovine antibodies were more likely to develop cow's-milk allergy later in life. Human milk also contains cytokines and growth factors that might account for its tolerance-promoting properties by modulating the activation of GALT and enhancing the function of the epithelial barrier. Most epidemiological studies support the view that breastfeeding protects against asthma and atopic dermatitis, or eczema, although this notion remains controversial. Nonetheless, the reinforcing effect of breast milk on mucosal barrier function in infants is robust and has special significance in families with a history of allergy.
As we currently understand it, oral tolerance is effected mainly through T-cell maturation events, such as anergy (a kind of cellular hibernation), clonal deletion (which removes T cells with undesirable targets) and, particularly, amplification of the immune system's voice of reason, the regulatory T (Treg) cell. As a result, healthy people have hardly any hyperactivated effector T cells (Teff) in their gut mucosa, scant mucosal production of proinflammatory IgG, and only low levels of IgG antibodies to food antigens in serum.
Food allergies vary in their severity and how swiftly symptoms appear. The immediate, life-threatening reactions experienced by some people (most often to peanuts) happen when the allergen binds to IgE-type antibodies, which then trigger the release of histamine, the compound responsible for acute inflammation with itching, sneezing and other allergy symptoms. Other types of food allergies result from IgG or IgM antibodies, or from so-called delayed-type hypersensitivity (not depending on antibodies). The latter reaction is typified by gluten-triggered celiac disease and may involve local dysregulation of both innate and adaptive immune functions. Delayed-type reactions may not show the hallmarks of classical inflammation that characterizes faster reactions.
Food allergies can be serious enough by themselves, but they can also announce the start of an "allergic march" that leads to antigen-triggered respiratory diseases. People who inherit a predisposition to atopy are at particular risk. Asthma and other atopic respiratory diseases have certainly become more common in developed countries during the past two decades.
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