chapter  2
34 Pages

Antigen-Presenting Cells

Allergic diseases, such as atopic dermatitis (AD), rhinitis (AR), and asthma (AA), are thought to result from a dysregulated immune response to commonly encountered antigens in genetically predisposed individuals. Immunological research into the mechanisms of allergy has identi¢ed cytokine production by T-helper 2 (Th2) e¡ector lymphocytes as being critical for orchestrating allergic in£ammation rich in eosinophils. Upon recognition of their cognate antigen, Th2 lymphocytes produce cytokines that regulate IgE synthesis, growth and activation of eosinophils and mast cells, and expression of endothelial cell adhesionmolecules.Despite thewealthof experimental data implying allergenspeci¢cTh2 cells as critical e¡ector cells in the allergic response, less information is available on the generation of these cells from naiveTh0 precursors.The ¢rst step in the allergic immune response is the uptake and presentation of allergen by professional antigen-presenting cells (APCs) such as dendritic cells (DCs),macrophages, and B lymphocytes. ImmatureDCs reside in the epithelia of the skin, upper and lower airways, and gut and have the potential to sense foreign antigens and nonspeci¢c in£ammatory tissue damage. Following recognition and uptake of Ag, mature DCs migrate to the T-cell-rich area of draining lymph nodes,display an array of Ag-derived peptides on the surface of major histocompatibility complex (MHC) molecules, and acquire the cellular specialization to select and activate naive Ag-speci¢cTcells. Alveolar macrophages (Ams) are exposed to inhaled antigens but normally suppress immune responses in the lung. This chapter deals with the role of DCs and AMs in the generation of the immune response to inhaled allergens.