Allergic rhinoconjunctivitis, asthma, and food allergy are some of the prototypical allergic diseases. Whereas allergies may develop at any age, allergic sensitization occurs predominantly early in life. Atopy is the inherited tendency to produce allergen-specific immunoglobulin (Ig) E antibodies. Food-specific IgE antibodies may appear in the very young child to herald an early presentation of clinical food allergies. Environmental allergen-specific IgE antibodies develop mostly after the age of 2, often leading to allergic rhinitis and/or allergic asthma in preschool or school-aged children. Although not all allergic diseases invariably develop in the same patient, in a sizeable number of children, the progressive sensitization to multiple antigens will result in sequential and often cumulative manifestations of atopy, a continuum that is known as the allergic march. It follows that allergic sensitization in childhood can have long-lasting effects throughout the life of the individual and implies a considerable burden to society as a whole.
The fundamental role of the immune system is to protect the host against microbial pathogens while maintaining tolerance to “self” and to harmless exogenous antigens. This task is accomplished through a series of interactions among elements of the innate and the adaptive immune systems and involves numerous pathways of recognition, activation, response, and memory. Deficient immune responses to pathogens can lead to increased susceptibility to infection, whereas a failure in the mechanisms of tolerance results in allergy or autoimmunity. On the other hand, an uncontrolled inflammatory response during the course of an infection can increase the risk of morbidity and mortality, and augmented tolerance can hamper tumor rejection.
At the cellular level, dendritic cells and T lymphocytes are central to the regulation of immune homeostasis (Fig. 188-1). Specific interactions between these 2 key players lead to the differentiation of naïve T cells into 1 of 3 T-helper (TH) subtypes (TH1, TH2, and TH17). These effector T cells are kept in check by another set of T cells, the regulatory T cells, of which there are several subtypes that presumably represent distinct lineages.
TH2 differentiation and allergen sensitization. Allergens are sampled directly by dendritic cells at the mucosal surfaces or access the submucosal dendritic cells through the epithelium. Activated dendritic cells mature and process the allergen and then present it to naïve T cells in the context of major histocompatibility complex (MHC) class II molecules. Differentiation of naïve T cells toward the TH2 phenotype is favored by the availability of interleukin-4 (IL-4) in the microenvironment. Cellular sources of this early IL-4 include basophils, mast cells, T cells, and eosinophils. TH2 cells produce IL-4 and IL-13 cytokines that promote immunoglobulin (Ig) class-switch recombination and IgE production by B cells. IgE diffuses locally and then is distributed systemically, where it can bind to high-affinity receptors present on mast cells and basophils, “sensitizing” them to respond when the host is reexposed to the allergen. While ...