Allergic rhinoconjunctivitis, asthma, and food allergy are some
of the prototypical allergic diseases. While allergies may develop
at any age, allergic sensitization (ie, development of IgE responses)
occurs predominantly early in life. Food-specific IgE antibodies
may appear in the very young 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 or the allergic marathon. 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
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 between elements of the innate and the
adaptive immune system and involves multiple 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 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.
191-1). Specific interactions between these two key players
lead to the differentiation of naïve T cells into one of
three 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
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
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 sensitization
is the ...
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