62 paRt III Immune Effector Mechanisms VISUALIZING CONCEPTS ADCC Immune Sensitized TpTH for Ige A Fc receptor activation activation b Neutrophil Immune pe Ty IgE-Mediated Hypersensitivity IgGI d Cytotoxic Immune Complex-Mediated Cell-Mediated Hypersensitivity Hypersensitivity Ag induces crosslinking of Ab directed against cell surface Ag-Ab complexes deposited Sensitized THl cells release antigens meditates cell various tissues induc cytokines that activat asophils with release of destruct ion via complement complement activation ar acrophages or Tc cells which ensuing inflammatory mediate direct cellular damage response mediated by massive Typical manifestations include Typical manifestations include Typical manifestations include manifestations include systemic anaphylaxis and blood transfusion reactions, localized Arthus reaction and yd2址计h=小间山油h =三 nd graft rejection allergies, and eczema vasculitis, glomeruLinephritis, heumatoid arthritis. and systemic lupus erythematosus FIGURE The four types of hypersensitive responses As it became clear that several different immune mecha- but it is important to point out that secondary effects blur the nisms give rise to hypersensitive reactions, P G. H. Gell and boundaries between the four categories. R.R. A Coombs proposed a classification scheme in which hypersensitive reactions are divided into four types. Three types of hypersensitivity ocur within the humoral branch IgE-Mediated (Type D) Hypersensitiv IgE-mediated(type D), antibody-mediated (type ID), and im- a type I hypersensitive reaction is induced by certain types of mune complex-mediated(type lID). A fourth type of hyper- antigens referred to as allergens, and has all the hallmarks of sensitivity depends on reactions within the cell-mediated a normal humoral response. That is, an allergen induces branch, and is termed delayed-type hypersensitivity, or DTH humoral antibody response by the same mechanisms type Iv). Each type involves distinct mechanisms, cells, and described in Chapter 11 for other soluble antigens, result mediator molecules( Figure 16-1). This classification scheme in the generation of antibody-secreting plasma cells has served an important function in identifying the mecha- memory cells. What distinguishes a type I hypersensitive stic differences among various hypersensitive reactions, response from a normal humoral response is that the plasmaAs it became clear that several different immune mecha￾nisms give rise to hypersensitive reactions, P. G. H. Gell and R. R. A. Coombs proposed a classification scheme in which hypersensitive reactions are divided into four types. Three types of hypersensitivity occur within the humoral branch and are mediated by antibody or antigen-antibody complexes: IgE-mediated (type I), antibody-mediated (type II), and im￾mune complex–mediated (type III). A fourth type of hyper￾sensitivity depends on reactions within the cell-mediated branch, and is termed delayed-type hypersensitivity, or DTH (type IV). Each type involves distinct mechanisms, cells, and mediator molecules (Figure 16-1). This classification scheme has served an important function in identifying the mecha￾nistic differences among various hypersensitive reactions, but it is important to point out that secondary effects blur the boundaries between the four categories. IgE-Mediated (Type I) Hypersensitivity A type I hypersensitive reaction is induced by certain types of antigens referred to as allergens, and has all the hallmarks of a normal humoral response. That is, an allergen induces a humoral antibody response by the same mechanisms as described in Chapter 11 for other soluble antigens, resulting in the generation of antibody-secreting plasma cells and memory cells. What distinguishes a type I hypersensitive response from a normal humoral response is that the plasma 362 PART III Immune Effector Mechanisms VISUALIZING CONCEPTS Type I IgE-Mediated Hypersensitivity Ag induces crosslinking of IgE bound to mast cells and basophils with release of vasoactive mediators Typical manifestations include systemic anaphylaxis and localized anaphylaxis such as hay fever, asthma, hives, food allergies, and eczema Typical manifestations include blood transfusion reactions, erythroblastosis fetalis, and autoimmune hemolytic anemia Typical manifestations include contact dermatitis, tubercular lesions and graft rejection Typical manifestations include localized Arthus reaction and generalized reactions such as serum sickness, necrotizing vasculitis, glomerulnephritis, rheumatoid arthritis, and systemic lupus erythematosus Ab directed against cell surface antigens meditates cell destruction via complement activation or ADCC Ag-Ab complexes deposited in various tissues induce complement activation and an ensuing inflammatory response mediated by massive infiltration of neutrophils Sensitized TH1 cells release cytokines that activate macrophages or TC cells which mediate direct cellular damage IgG-Mediated Cytotoxic Hypersensitivity Immune Complex-Mediated Hypersensitivity Cell-Mediated Hypersensitivity Type II Type III Type IV Allergen Allergen￾specific IgE Fc receptor for IgE Fc receptor Degranulation C3b C3b C3b Antigen Immune complex Complement activation Complement activation Immune complex C C Neutrophil Activated macrophage Cytokines Sensitized TDTH ADCC Cytotoxic cell Surface Target antigen cell FIGURE 16-1 The four types of hypersensitive responses