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FIGURE 16-19

30 40 50 60 Days after BCG infection

Experimental demonstration of the role of IFN-7 in host defense against intracellular pathogens. Knockout mice were produced by introducing a targeted mutation in the gene encoding IFN-7. The mice were then infected with 107 colony-forming units of attenuated Mycobacterium bovis (BCG) and their survival monitored. [Adapted from D. K. Dalton et al, 1993, Science 259:1739.]

This complex is internalized by antigen-presenting cells in the skin (e.g., Langerhans cells), then processed and presented together with class II MHC molecules, causing activation of sensitized TH1 cells. In the reaction to poison oak, for example, a pentadecacatechol compound from the leaves of the plant forms a complex with skin proteins. When TH cells react with this compound appropriately displayed by local antigen-presenting cells, they differentiate into sensitized Th1 cells. A subsequent exposure to pentadecacatechol will elicit activation of TH1 cells and induce cytokine production (Figure 16-20). Approximately 48-72 h after the second exposure, the secreted cytokines cause macrophages to accumulate at the site. Activation of these macrophages and release of lytic enzymes result in the redness and pustules that characterize a reaction to poison oak.

SUMMARY

■ Hypersensitive reactions are inflammatory reactions within the humoral or cell-mediated branches of the immune system that lead to extensive tissue damage or even death. The four types of hypersensitive reaction generate characteristic effector molecules and clinical manifestations.

■ A type I hypersensitive reaction is mediated by IgE antibodies, whose Fc region binds to receptors on mast cells or blood basophils. Crosslinkage of the fixed IgE by allergen leads to mast cell or basophil degranulation with release of pharmacologically active mediators. The principal effects of these mediators are smooth-muscle contraction and vasodilation. Clinical manifestations of type I reactions include potentially life-threatening systemic anaphylaxis and localized responses such as hay fever and asthma.

■ A type II hypersensitive reaction occurs when antibody reacts with antigenic determinants present on the surface of cells, leading to cell damage or death through complement-mediated lysis or antibody-dependent cell-mediated cyto-toxicity (ADCC). Transfusion reactions and hemolytic disease of the newborn are type II reactions.

■ A type III hypersensitive reaction is mediated by the formation of immune complexes and the ensuing activation of complement. Complement split products serve as immune effector molecules that elicit localized vasodilation and chemotactically attract neutrophils. Deposition of immune complexes near the site of antigen entry can induce an Arthus reaction, in which lytic enzymes released by the accumulated neutrophils and the complement membrane-attack complex cause localized tissue damage.

■ A type IV hypersensitive reaction involves the cell-mediated branch of the immune system. Antigen activation of sensitized Th1 cells induces release of various cytokines that cause macrophages to accumulate and become activated. The net effect of the activation of macrophages is to release lytic enzymes that cause localized tissue damage.

Poison oak

(Toxicodendron radicans)

Poison oak

(Toxicodendron radicans)

Pentadecacatechol «

Pentadecacatechol «

Langerhans Cell Apc

Langerhans cell (APC)

Lytic enzymes

\ Tissue macrophage

Langerhans cell (APC)

FIGURE 16-20

Development of delayed-type hypersensitivity reaction after a second exposure to poison oak. Cytokines such as IFN-7, macrophage-chemotactic factor (MCF), and migration-inhibition factor (MIF) released from sensitized TH1 cells mediate this reaction. Tissue damage results from lytic enzymes released from activated macrophages.

Lytic enzymes

\ Tissue macrophage

Tissue macrophage

Tissue macrophage

FIGURE 16-20

Development of delayed-type hypersensitivity reaction after a second exposure to poison oak. Cytokines such as IFN-7, macrophage-chemotactic factor (MCF), and migration-inhibition factor (MIF) released from sensitized TH1 cells mediate this reaction. Tissue damage results from lytic enzymes released from activated macrophages.

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