ATOPY
Clinical
allergic diseases are predominately type I, or IgE mediated. Approximately 40
percent of people in Western nations are inclined toward an exaggerated IgE
response to multiple environmental aller-gens such as pollen or animal dander.
This allergic state, known as atopy,
is the result of multiple genetic and environmental factors.
Our
current understanding of the devel-opment of an IgE response favors a TH2
T-cell induction. When specific inhaled, ingested, or absorbed proteins, or
aller-gens, appropriately stimulate this subset of the T-cell population, a
series of cellular reactions occurs that leads to IgE antibody production.
Inhalation
of most proteins does not cause IgE-mediated responses, whereas a limited
number of small protein aller-gens can elicit such reactions. Although the
mechanism of allergic induction is not completely clear, some general
prin-ciples have emerged. Allergens presented transmucosally at very low doses
induce IgE responses by TH2 cells. This subset of cells produces the
primary cytokines, interleukin-4 (IL-4) and interleukin-13 (IL-13). These
interleukins interact with receptors on B lymphocyte cell surfaces, which
promote class switching to the IgE antibody subclass. The subsequent class
switch produces antigen-specific IgE anti-bodies with specificity toward common
allergens such as pollen, animal dander, food, or venom.
Genetic
studies of atopic families have identified regions on chromosome 11q and 5q
that affect IgE production. Chromosome 5 contains multiple genes, including
those for IL-4, IL-5, and granulocyte-macrophage colony-stimulating factor.
Eosinophil sur-vival and mast cell proliferation are just a few pro-allergic
effects of these cytokines. Chromosome 11 encodes the beta subunit of the high-affinity
IgE receptor. Increased expression of this receptor on mast cells leads to a
more vehement response to small numbers of antigens. This increased expression
explains how exposure to min-ute amounts of allergen, such as venom from a
stinging insect, can produce sys-temic anaphylaxis.
Although
atopy has a strong genetic component, environmental factors best explain the
recent global trend toward
increased prevalence of allergic disease. Predictive factors include the
following:
(1) decreased exposure to infectious dis-ease
during early childhood, (2) changes in diet, (3) higher levels of allergen
expo-sure, and (4) increased environmental pollution. Of these factors,
variances in exposure to infectious disease appear to have
the greatest correlation with atopy. Epidemiological studies point out a
nega-tive association between atopic disease in children and a history of
measles or hepa-titis A virus infection. It is hypothesized that infections
such as these tilt the pro-duction of cytokines toward interferon gamma (IFN-γ) and the TH1
cytokines, thereby decreasing production of TH2 allergic cytokines
such as IL-4. This the-ory’s attractiveness may be its ability to explain the
global increase in atopy due to decreased infection rates in Western-ized
regions with aggressive vaccination programs. Current research trials use this
theory with protein vaccines that promote TH1 responses to shift the
immune sys-tem away from this allergic phenotype. We highlight the common
clinical manifestations of atopy and dem-onstrate how immunological reactivity
to key antigens underscores each condition. Although the Gell and Coombs
classifica-tion is not universally applicable, the fun-damental immunological
processes apply in most of the common clinical hypersen-sitivity states discussed next.
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