Allergic Synthesis

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The mechanism behind an allergic reaction consists of two phases. The first phase involves the initial sensitization, where an antigen is encountered by antigen presenting cells (APC) and processed for presentation to naïve T cells. The antigen can be introduced through various routes, including the gastrointestinal tract (food allergens) and lung epithelial (pollens). Animal studies have suggested an additional route through skin contact (REF), and this is supported by the previously mentioned studies regarding atopic dermatitis as a risk factor for food allergy development, However, direct evidence of this occurring in humans is limited to a number of case studies lacking supporting immunological data (REF). Accumulating evidence suggests…show more content…
For this to occur, B cell receptor activation by the antigen, the presence of a Th2 cytokine environment (IL-4), and signaling through CD40 is required (REF). Although these signals can be provided by T cells, T cell-independent class switching has also been described, where other cells including basophils and mast cells take on this role. The resulting antigen-specific IgE is a key player in the second phase of allergic inflammation, and therefore also a therapeutic target. Secreted locally in tissue and systemically in peripheral blood, IgE molecules are captured by IgE receptors on a variety of cells. Two types of IgE receptors exist. Low affinity receptors (CD23) are present on B cells, T cells, Langerhan cells, monocytes, macrophages, platelets, follicular DCs and eosinophils (Delepesse 1991 adv Immunol, Soussi 1998 ) and play an important role in IgE production regulation. Binding of IgE or IgE-immune complexes induces a negative feedback signal preventing further IgE synthesis (Sherr, JI 1989). In contrast, soluble forms of CD23 up-regulate IgE production by B cells (need human ref). High affinity receptors (FceRI) are present on basophils, mast cells and plasmacytoid dendritic cells and their expression is directly related to the amount of IgE molecules in the cell’s environment (Macglashan JI 1997).…show more content…
Although many food allergies tend to resolve in early childhood, there is still a significant impact on the quality of life of the child and their caregivers. This is exemplified by studies that have shown an increased risk of bullying in school children with food allergies (Lieberman 2010 AAAI, Shemesh Ped 2013, Sicherer 2014 JACI). In addition, food allergies constitute a significant burden on both social and economical resources in attempts to manage the disease. Food allergies that tend to persist, including shellfish, peanut, and tree nut allergies, have a continued significant impact on the quality of life, not only due to the strict dietary restrictions but also the constant fear of accidental exposure. A study investigating the economic impact of childhood food allergy in the United States estimated the overall cost to be $24.8 billion annually, averaging at $4184 per child. Approximately $4.3 billion was attributed to direct medical costs including clinician visits, emergency department visits, and hospitalizations. Other costs were borne to lost labour productivity, out of pocket and opportunity costs (Gupta 2013 JAMA Ped). The Europrevall study estimated the financial burden of food allergy across 9 European countries by comparing health care costs between food allergic individuals and

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