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Mechanisms of Allergic Sensitization and Desensitization in a Mouse Model

Gudimetla, Vishnu
http://orcid.org/0000-0002-9215-1345
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1529667182585476

Abstract Details

2017, MS, University of Cincinnati, Medicine: Immunology.
Food allergy is defined as an abnormal immune response following ingestion of food-based allergens. Ingestion of a food allergen, by a sensitized individual, can induce shock and cause the development of different localized responses such as urticaria, wheezing, cramping, vomiting, or diarrhea. Food allergy is a type I hypersensitivity that is mast cell- and basophil-dependent; an absorbed allergen binds to IgE associated with the high-affinity IgE receptor, Fc?RI, on the cell surface of mast cells and basophils leading to the secretion of compounds causing signs and symptoms. However, the role of mast cells, along with the mediators released, is not well understood. Two mouse models were utilized to investigate the clinical response of food allergy as determined by measuring hypothermia and the development of diarrhea. One model, the active model, is sensitization through injection of a food antigen with an adjuvant. Sensitized mice were then orally challenged two times a week until both hypothermia and diarrhea were observed. The second model, the passive model, requires an intravenous injection of antigen-specific IgE monoclonal antibody (mAb) twenty-four hours prior to an oral challenge with the specific antigen. Previous studies in our lab indicated that an allergic response, modeled in mice utilizing the active immunization method, induces both hypothermia and diarrhea in response to an oral antigen challenge. However, the passive immunization model induces hypothermia without diarrhea. This led to the hypothesis that changes within the gastrointestinal tract induced by active sensitization were required for the development of diarrhea. Our results indicated that mice sensitized to egg white protein (EW), using the active model of sensitization, developed diarrhea in response to a challenge with TNP-BSA after sensitization with IgE anti-TNP mAb. This contrasted with mice that were not actively immunized and only developed a temperature drop to a similar IgE anti-TNP/TNP-BSA challenge. These observations provide support for the idea that organ specific changes, induced by prior sensitization with an antigen can facilitate the development of an organ specific local response such as diarrhea to a separate and systemic allergen. Treating allergy mainly focused on avoidance of the allergen but another method, oral immunotherapy, has been suggested. Oral immunotherapy, is carried out by increasing doses of an allergen until a large dose does not elicit a response and the patient has been desensitized. However, this process can take weeks to month, may not work in some individuals, and is temporary. Efforts to understand desensitization have discovered mechanisms associated with an establishment of a non-responsive state however, the effect of desensitization on mast cells has not been understood. We hypothesized that mast cell degranulation and/or sensitivity to mast cell mediators, as measured by a temperature drop, might be decreased. Our studies show degranulation of mast cells increased and decreased sensitivity to histamine was a short-lived phenomenon. Additionally, treatment with propranolol one day after desensitization re-established a temperature response. These observations suggested novel mechanisms, such as decreased sensitivity to vasoactive mediators and an induction of an adrenergic response in desensitization.
Jonathan Katz, Ph.D. (Committee Chair)
Patricia Fulkerson, Ph.D. (Committee Member)
Simon Hogan, Ph.D. (Committee Member)
64 p.
Immunology
Food Allergy; Mast Cells; IgE; Sensitization; Desensitization; Mouse Model

Recommended Citations

Citations

  • Gudimetla, V. (2017). Mechanisms of Allergic Sensitization and Desensitization in a Mouse Model [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1529667182585476

    APA Style (7th edition)

  • Gudimetla, Vishnu. Mechanisms of Allergic Sensitization and Desensitization in a Mouse Model. 2017. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1529667182585476.

    MLA Style (8th edition)

  • Gudimetla, Vishnu. "Mechanisms of Allergic Sensitization and Desensitization in a Mouse Model." Master's thesis, University of Cincinnati, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1529667182585476

    Chicago Manual of Style (17th edition)

ucin1529667182585476
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This open access ETD is published by University of Cincinnati and OhioLINK.