In the final step of the sensitization phase, the variable region of IgE binds to FceR receptors present on the surface of mast cells. IgE antibodies and mast cells survive in the tissue, where they are primed for a second encounter with the allergen.

IgE binds to other cells such as basophils and activated eosinophils, which secrete more IL-4. This encourages the class-switching and subsequent production of IgE of nearby B-cells.

Re-exposure to the same allergen causes the antigen to bind directly to the IgE variable regions on mast cells. A single bound IgE antibody does not incite hypersensitivity, but when two IgE antibodies bind to an antigen molecule, the mast cell undergoes de-granulation. This process releases primary mediators such as vasoactive amines into the tissue, as well as secondary mediators like leukotrienes.