Fig.1. Sensitization to a food allergen through the unified airway
See description in the text. AG - allergens, DCs - dendritic cells, APC - allergen-presenting cells, Th2 - type 2 helper T cells, Tfh - follicular helper T cells, fDC - follicular dendritic cells, ILC2 - group 2 innate lymphoid cells, NEC - neuroendocrine cells, TLR - toll-like receptors
A food allergen that passes the epithelial barriers is processed by dendritic cells (DCs), i.e., allergen-presenting (APC) cells, which in turn migrate to draining lymph nodes, where they present allergen-derived peptides on HLA class II molecules to naïve T cells. The naïve T cells differentiate into Th2 cells and follicular helper T (Tfh) cells. Th2 cells produce type 2 cytokines such as IL-4, IL-5, IL-9, IL-13, IL-33 and drive allergic response [36; 37; 38; 39]. Tfh cells secrete IL-21, IL-4, IL-13, which promote IgE class switch recombination in B cells, plasma cell maturation, and allergen-specific IgE production. The IgE antibodies may contribute to the allergic inflammation in the unified airway, e.g., in allergic rhinitis or asthma. In this case, the allergen-specific IgE antibodies bind to FcεRI molecules on mast cells and basophils, resulting in their degranulation and allergic inflammation development due to histamine and other mediators of innate effector cells. Simultaneously, shaping two types of allergen-specific memory cells, (1) memory T cells and (2) memory B cells, occurs. These memory cells and IgE antibodies get into the bloodstream and then into the gastrointestinal tract.
Oral tolerance, an antipode of food allergies and a form of allergen tolerance, is a physiologic process of nutrient absorption with no adverse reaction. However, oral tolerance depends on multiple factors, which can maintain or destabilize it under the everyday entry of food proteins, dynamic gut microbiota, changing signals from neuro molecules, and continuous trafficking of pro-inflammatory cells and molecules [40]. Furthermore, it is unknown if feeding allergens can also induce true immune tolerance after generating a memory immune response [41].