Exposure to sufficiently high allergen levels of some allergens appears to protect
against the development of allergic diseases, and has also been used to treat
established allergic diseases. A reduced prevalence of sensitization and, in some
cases, asthma was reported among individuals living in homes with high allergen
levels. Furthermore, allergic patients treated with high allergen doses during
immunotherapy experienced improved allergic symptoms. The mechanisms for
how high allergen exposure may prevent disease are not known and thus, a model
in which these mechanisms could be studied in detail is warranted. The objective
of this thesis was to model and further characterize the phenomenon of high
allergen dose-dependent protection against the development of allergic responses,
using a mouse model of epicutaneous sensitization. The impact of exposure to a
high dose of cat dander in established allergic disease was also evaluated.
Epicutaneous exposure to a high dose of cat dander (150 μg) prevented airway
inflammation and airway hyperresponsiveness in genetically different strains of
mice, including Th2 prone BALB/c mice. The protective effects against airway
inflammation appeared to wane between 10 and 120 days after exposure. When
the high dose of cat dander was applied with a sensitizing dose of peanut, peanut induced anaphylaxis was prevented. Exposure to a high dose of another allergen,
ovalbumin, was also able to prevent the development of allergic airway disease.
In contrast, the high dose of cat dander did not improve established states of
allergic disease. Thus, in our mouse model, a high dose of cat dander prevented
the development of allergic responses and reflected characteristics of the
phenomenon reported in humans. As such, this model may be useful for
investigating mechanisms and potential prophylactic options for allergic diseases.
As the high dose of cat dander either had no effect or worsened established
allergic responses in our model, it is possible that the dose was not high enough to
improve disease in sensitized mice. It is also possible that established disease
cannot be modified by epicutaneous exposure. / Thesis / Master of Science (MSc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/20500 |
| Date | January 2016 |
| Creators | Singh, Tarandeep |
| Contributors | Larché, Mark, Medical Sciences (Molecular Virology and Immunology Program) |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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