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].