The eotaxin receptor on eosinophils, CCR3, is quite promiscuous and binds other CC chemokines, including CCL5, CCL7, and CCL13, which also induce eosinophil chemotaxis and activation. Identical or similar chemokines stimulate mast cells and basophils. For example, eotaxins attract basophils and cause their degranulation. TH2 cells also carry the receptor CCR3 and migrate toward eotaxins.
Basophils are also present at the site of an inflammatory reaction, and growth factors for basophils are very similar to those for eosinophils; they include IL-3, IL-5, and GM-CSF. There is evidence for reciprocal control of the maturation of the stem-cell population into basophils or eosinophils. For example, TGF-β in the presence of IL-3 suppresses eosinophil differentiation and enhances that of basophils. Basophils are normally present in very low numbers in the circulation and seem to have a similar role to that of eosinophils in defense against pathogens. Like eosinophils, they are recruited to the sites of IgE-mediated allergic reactions. Basophils express high-affinity FcεRI on their cell surfaces and so have IgE bound. On activation by antigen binding to IgE or by cytokines, they release histamine from their granules and also produce IL-4 and IL-13.
Eosinophils, mast cells, and basophils can interact with each other. Eosinophil degranulation releases major basic protein (see Fig. 14.10), which in turn causes the degranulation of mast cells and basophils. This effect is augmented by any of the cytokines that affect eosinophil and basophil growth, differentiation, and activation, such as IL-3, IL-5, and GM-CSF.
14-9 IgE-mediated allergic reactions have a rapid onset but can also lead to chronic responses.
Under laboratory conditions, the clinical response of a sensitized individual to challenge by intradermal allergen or inhalation of allergen can be divided into an ‘immediate reaction’ and a ‘late-phase reaction’ (Fig. 14.11). The immediate
Fig. 14.11 Allergic reactions in response to test antigens can be divided into an immediate response and a late-phase response.
Left panel: the response to an inhaled antigen can be divided into early and late responses. An asthmatic response in the lungs with narrowing of the airways caused by the constriction of bronchial smooth muscle and development of edema can be measured as a fall in the peak expiratory flow rate (PEFR). The immediate response peaks within minutes after antigen inhalation and then subsides, returning to near baseline PEFR. Six to eight hours after antigen challenge, there can be a late-phase response that also results in a fall in the PEFR. The immediate response is caused by the direct effects on blood vessels, nerves, and smooth muscle of rapidly metabolized mediators such as histamine and lipid mediators released by mast cells. The late-phase response is caused by the continued production of these mediators, by the production of vasoactive compounds that dilate blood vessels, and by recruitment of lymphocytes and myeloid cells, which together lead to the production of edema. Right panel: a wheal-and-flare allergic reaction develops within a minute or two of intradermal injection of antigen and lasts for up to 30–60 minutes. The more widespread edematous response characteristic of the late phase develops approximately 6 hours later and can persist for up to 2 or 3 days. The photograph shows an intradermal skin challenge with allergen resulting in a wheal-and-flare (early-phase) reaction observed 15 minutes after allergen challenge (left) and a late-phase reaction occurring 6 hours after challenge (right). The allergen was grass pollen extract. Photograph courtesy of S.R. Durham.