Allergic reactions are triggered when allergens cross-link preformed IgE bound to the high-affinity receptor FcεRI on mast cells. Mast cells line external mucosal surfaces and serve to alert the immune system to local infection. Once activated, they induce inflammatory reactions by secreting pharmacological mediators such as histamine stored in preformed granules and by synthesizing prostaglandins, leukotrienes, and platelet-activating factor from the plasma membrane. They also release various cytokines and chemokines after activation. In the case of an allergic reaction, they provoke unpleasant reactions to innocuous antigens that are not associated with invading pathogens that need to be expelled. The consequences of IgE-mediated mast-cell activation depend on the dose of antigen and its route of entry; symptoms range from the swollen eyes and rhinitis associated with contact of pollen with the conjunctiva of the eye and the nasal epithelium, to the life-threatening circulatory collapse that occurs in anaphylaxis (Fig. 14.8). The immediate reaction caused by mast-cell degranulation is followed, to a greater or lesser extent depending on the disease, by a more sustained inflammation, which is due to the recruitment of other effector leukocytes, notably TH2 lymphocytes, eosinophils, and basophils.
Fig. 14.8 Mast-cell activation has different effects on different tissues.
Increased ˜uid in tissues causing increased ˜ow of lymph to lymph nodes, increased cells and protein in tissues, increased effector response in tissues Hypotension potentially leading to anaphylactic shock Congestion and blockage of airways (wheezing, coughing, phlegm) Swelling and mucus secretion in nasal passages Ocular itching Sneezing Expulsion of gastrointestinal tract contents (diarrhea, vomiting) Decreased airway diameter, increased mucus secretion Eyes, nasal passages, and airways Mast-cell activation and granule release Increased ˜uid secretion, increased peristalsis Increased blood ˜ow, increased permeability Gastrointestinal tract Blood vessels 14-6 Most IgE is cell-bound and engages effector mechanisms of the immune system by pathways different from those of other antibody isotypes.
Antibodies engage effector cells such as mast cells by binding to receptors specific for their Fc constant regions. Most antibodies engage Fc receptors only after their antigen-binding sites have bound specific antigen, forming an immune complex of antigen and antibody. IgE is an exception, because it is captured by the high-affinity Fcε receptor (FcεRI) in the absence of bound antigen. This means that, unlike other antibodies, which are found mainly in body fluids, IgE is mostly found fixed on cells that carry this receptor—mast cells in tissues, and basophils in the circulation and at sites of inflammation. The ligation of the cell-bound IgE antibody by specific multivalent antigen triggers the activation of these cells at the sites of antigen entry into the tissues. The release from these activated mast cells of inflammatory lipid mediators, cytokines, and chemokines at sites of IgE-triggered reactions recruits eosinophils and basophils to augment the allergic response. It also recruits TH2 cells, which can then mount a local type 2 cellular response.