It is estimated that 20% to 30% of immediate hypersensitivity reactions are triggered by nonantigenic stimuli such as temperature extremes and exercise, and do not involve TH2 cells or IgE. It is believed that in these cases mast cells are abnormally sensitive to activation by various nonimmune stimuli.
The incidence of many allergic diseases is increasing in developed countries and seems to be related to a decrease in infections during early life. These observations have http://ebooksmedicine.net
Fig. 5.13 Phasesofimmediatehypersensitivityreactions.(A)Kineticsoftheimmediateandlate-phasereactions.Theimmediatevascularandsmoothmusclereactiontoallergendevelopswithinminutesafterchallenge(allergenexposureinapreviouslysensitizedindividual),andthelate-phasereactiondevelops2to24hourslater.Theimmediatereaction(B)ischaracterizedbyvasodilation,congestion,andedema,andthelate-phasereaction(C)ischaracterizedbyaninflammatoryinfiltraterichineosinophils,neutrophils,andTcells.(Courtesy of Dr. Daniel Friend, Department of Pathology, Brigham and Women’s Hospital, Boston,
Massachusetts.) led to an idea, sometimes called the hygiene hypothesis, that early childhood and even prenatal exposure to microbial antigens educates the immune system in such a way that subsequent pathologic responses against common environmental allergens are prevented. Thus, too much hygiene in childhood may increase allergies later in life. The idea that early childhood exposure to antigens may reduce later allergies against those antigens has received support from clinical trials demonstrating that exposing infants to peanuts reduces the incidence of peanut allergy later in life.
Often, the IgE-triggered reaction has two well-defined phases (
Fig. 5.13 ): (1) the immediate response, which is stimulated by mast cell granule contents and lipid mediators and is characterized by vasodilation, vascular leakage, and smooth muscle spasm, usually evident within 5 to 30 minutes after exposure to an allergen and subsiding by 60 minutes; and (2) a second, late-phase reaction stimulated mainly by cytokines, which usually sets in 2 to 8 hours later, may last for several days, and is characterized by inflammation as well as tissue destruction, such as mucosal epithelial cell damage. The dominant inflammatory cells in the late-phase reaction are neutrophils, eosinophils, and lymphocytes, especially TH2 cells. Neutrophils are recruited by various chemokines; their roles in inflammation were described in Chapter 3. Eosinophils are recruited by eotaxin and other chemokines released from epithelium and are important effectors of tissue injury in the late-phase response. Eosinophils produce major basic protein and eosinophil cationic protein, which are toxic to epithelial cells, and LTC4 and platelet-activating factor, which promote inflammation. The TH2 cells produce cytokines that have multiple actions, as described earlier. These recruited leukocytes can amplify and sustain the inflammatory response, even in the absence of continuous allergen exposure. In addition, inflammatory leukocytes are responsible for much of the epithelial cell injury in immediate hypersensitivity. Because inflammation is a major component of many allergic diseases, notably asthma and atopic dermatitis, therapy includes anti-inflammatory drugs such as corticosteroids.
An immediate hypersensitivity reaction may occur as a systemic disorder or as a local reaction (