Immunologic changes during the course of AIT. Starting with the first injection, decreases in mast cell and basophil activity, degranulation and tendency for systemic anaphylaxis degranulation takes place within the first hours. This is followed by generation of allergen-specific Treg and Breg cells and suppression of allergen-specific Th1 and Th2 cells. Specific IgE shows an early increase and decreases relatively late. These events are in parallel to increases of IgG4 that continuously increases as long as the treatment continues. After several months, the allergen-specific IgE/IgG4 ratio decreases. After a few months, decreases in tissue mast cells and eosinophils and release of their mediators and skin late phase response occurs. A significant decrease in type I skin test reactivity is also observed relatively late in the course. It has to be noted that there is significant variation between donors and protocols.