Gell and Coombs Classification
Several forms of hypersensitive reaction can be distinguished, reflecting differences in the effector molecules generated in the course of the reaction. In immediate hypersensitive reactions, different antibody isotypes induce different immune effector molecules. IgE antibodies, for example, induce mast-cell degranulation with release of histamine and other biologically active molecules. IgG and IgM antibodies, on the other hand, induce hypersensitive reactions by activating complement. The effector molecules in the complement reactions are the membrane-attack complex and such complement split products as C3a, C4a, and C5a. In delayed-type hypersensitivity reactions, the effector molecules are various cytokines secreted by activated TH or TC cells.
VISUALIZING CONCEPTS
VISUALIZING CONCEPTS
Fc receptor for IgE
Allergen specific
Allergen
Allergen specific
Degranulation
Degranulation
Type I
Cytotoxic
Fc receptor v Surface ^lai-grt^ antigen cell
Complement activation
ADCC
Cytotoxic
Fc receptor v Surface ^lai-grt^ antigen cell
Complement activation
Immune complex
Type II
Complement activation ^
Immune complex NWC3b)
Complement activation ^
Type III
o Antigen o Antigen
Sensitized Tdth
Sensitized Tdth
Cytokines
Cytokines
- Activated macrophage Type IV
IgE-Mediated Hypersensitivity
IgG-Mediated Cytotoxic Hypersensitivity
Immune Complex-Mediated Hypersensitivity
Cell-Mediated Hypersensitivity
Ag induces crosslinking of IgE bound to mast cells and basophils with release of vasoactive mediators
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 Th 1 cells release cytokines that activate macrophages or Tq cells which mediate direct cellular damage
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 localized Arthus reaction and generalized reactions such as serum sickness, necrotizing vasculitis, glomerulnephritis, rheumatoid arthritis, and systemic lupus erythematosus
Typical manifestations include contact dermatitis, tubercular lesions and graft rejection
FIGURE 16-1
The four types of hypersensitive responses.
As it became clear that several different immune mechanisms 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 immune 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 mechanistic differences among various hypersensitive reactions, but it is important to point out that secondary effects blur the boundaries between the four categories.
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