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

Allergen

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

Immune complex

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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