Hypersensitive Reactions CHAPTER 16 cells secrete IgE. This class of antibody binds with high affin- crease and remain high until the parasite is successfully ity to Fc receptors on the surface of tissue mast cells and cleared from the body. Some persons, however, may have an blood basophils. Mast cells and basophils coated by igE are abnormality called atopy, a hereditary predisposition to the said to be sensitized. A later exposure to the same allergen development of immediate hypersensitivity reactions against cross-links the membrane-bound IgE on sensitized mast cells common environmental antigens. The IgE regulatory defects and basophils, causing degranulation of these cells(figure suffered by atopic individuals allow nonparasitic antigens to 16-2). The pharmacologically active mediators released from stimulate inappropriate igE production, leading to tissue- the granules act on the surrounding tissues. The principal damaging type I hypersensitivity. The term allergen refers effects-vasodilation and smooth-muscle contraction-may specifically to nonparasitic antigens capable of stimulating be either systemic or localized, depending on the extent of type I hypersensitive responses in allergic individuals mediator release The abnormal IgE response of atopic individuals is at least partly genetic-it often runs in families. Atopic individuals have There Are Several components abnormally high levels of circulating IgE and also more tha of Type I Reactions normal numbers of circulating eosinophils. These individuals are more susceptible to allergies such as hay fever, eczema, and As depicted in Figure 16-2, several components are critical to asthma. The genetic propensity to atopic responses has been development of type I hypersensitive reactions. This section mapped to several candidate loci. One locus, on chromosome will consider these components first and then describe the 5q, is linked to a region that encodes a variety of cytokines, mechanism of degranulation including IL-3, IL-4, IL-5, IL-9, IL-13, and GM-CSE A second ALLERGENS locus, on chromosome 11q is linked to a region that encodes the chain of the high-affinity IgE receptor. It is known that inher- The majority of humans mount significant IgE responses ited atopy is multigenic and that other loci probably also are only as a defense against parasitic infections. After an indi- involved. Indeed, as information from the Human Genome vidual has been exposed to a parasite, serum igE levels in- Project is analyzed, other candidate genes may be revealed. B cel Tu cell Allergen Small blood vessel Fc receptor amines y。必 Mucous g 名 Blood platelets 9+Aller Plasma cell Sensitized mast cell Degranulation Allergen IGURE 16-2 General mechanism underlying a type I hypersens- tor ) Second exposure to the allergen leads to crosslinking of the ve reaction. Exposure to an allergen activates B cells to form IgE- bound ige, triggering the release of pharmacologically active media- secreting plasma cells. The secreted igE molecules bind to IgE- tors, vasoactive amines, from mast cells and basophils. The media specific Fc receptors on mast cells and blood basophils. ( Many mol- tors cause smooth-muscle contraction, increased vascular perme- cules of igE with various specificities can bind to the igE-Fc recep- ability, and vasodilationcells secrete IgE. This class of antibody binds with high affin￾ity to Fc receptors on the surface of tissue mast cells and blood basophils. Mast cells and basophils coated by IgE are said to be sensitized. A later exposure to the same allergen cross-links the membrane-bound IgE on sensitized mast cells and basophils, causing degranulation of these cells (Figure 16-2). The pharmacologically active mediators released from the granules act on the surrounding tissues. The principal effects—vasodilation and smooth-muscle contraction—may be either systemic or localized, depending on the extent of mediator release. There Are Several Components of Type I Reactions As depicted in Figure 16-2, several components are critical to development of type I hypersensitive reactions. This section will consider these components first and then describe the mechanism of degranulation. ALLERGENS The majority of humans mount significant IgE responses only as a defense against parasitic infections. After an indi￾vidual has been exposed to a parasite, serum IgE levels in￾crease and remain high until the parasite is successfully cleared from the body. Some persons, however, may have an abnormality called atopy, a hereditary predisposition to the development of immediate hypersensitivity reactions against common environmental antigens. The IgE regulatory defects suffered by atopic individuals allow nonparasitic antigens to stimulate inappropriate IgE production, leading to tissue￾damaging type I hypersensitivity. The term allergen refers specifically to nonparasitic antigens capable of stimulating type I hypersensitive responses in allergic individuals. The abnormal IgE response of atopic individuals is at least partly genetic—it often runs in families.Atopic individuals have abnormally high levels of circulating IgE and also more than normal numbers of circulating eosinophils. These individuals are more susceptible to allergies such as hay fever, eczema, and asthma. The genetic propensity to atopic responses has been mapped to several candidate loci. One locus, on chromosome 5q, is linked to a region that encodes a variety of cytokines, including IL-3, IL-4, IL-5, IL-9, IL-13, and GM-CSF. A second locus,on chromosome 11q,is linked to a region that encodes the chain of the high-affinity IgE receptor. It is known that inher￾ited atopy is multigenic and that other loci probably also are involved. Indeed, as information from the Human Genome Project is analyzed, other candidate genes may be revealed. Hypersensitive Reactions CHAPTER 16 363 Memory cell Plasma cell Sensitized mast cell B cell TH cell Allergen CD4 IL-4 Allergen￾specific IgE Fc receptor for IgE + Allergen Allergen Eosinophil Sensory–nerve endings Blood platelets Mucous gland Vasoactive amines Small blood vessel Smooth muscle cell Degranulation FIGURE 16-2 General mechanism underlying a type I hypersensi￾tive reaction. Exposure to an allergen activates B cells to form IgE￾secreting plasma cells. The secreted IgE molecules bind to IgE￾specific Fc receptors on mast cells and blood basophils. (Many mol￾ecules of IgE with various specificities can bind to the IgE-Fc recep￾tor.) Second exposure to the allergen leads to crosslinking of the bound IgE, triggering the release of pharmacologically active media￾tors, vasoactive amines, from mast cells and basophils. The media￾tors cause smooth-muscle contraction, increased vascular perme￾ability, and vasodilation.