24–72 hours A TH1 effector cell recognizes antigen and releases cytokines, which act on vascular endothelium Recruitment of phagocytes and plasma to site of antigen injection causes visible lesion Antigen is injected into subcutaneous tissue and processed by local antigen-presenting cells
Fig. 14.19 Cellular hypersensitivity reactions. These responses are mediated by T cells and require 3–5 days or more to develop. They can be grouped into three syndromes, according to the route by which antigen passes into the body. In delayed-type hypersensitivity the antigen is injected into the skin; in contact hypersensitivity it is absorbed into the skin; and in gluten-sensitive enteropathy it is absorbed by the gut. In contact hypersensitivity, vesicles commonly form. They represent accumulations of fluid in small blister-like lesions at the level of the basement membrane between the dermis and epidermis. Their formation at this location is probably the result of antigen penetrating the epidermis, accumulating at the basement membrane, and inducing a local inflammatory response with edema fluid. DNFB (dinitrofluorobenzene) is a sensitizing agent that can cause contact hypersensitivity.
MOVIE 14.1
Fig. 14.20 The stages of a delayed-type hypersensitivity reaction. The first phase involves uptake, processing, and presentation of the antigen by local antigen-presenting cells. In the second phase, TH1 cells that have been primed by a previous exposure to the antigen migrate into the site of injection and become activated. Because these specific cells are rare, and because there is little inflammation to attract cells into the site, it can take several hours for a T cell of the correct specificity to arrive. These cells release mediators that activate local endothelial cells, which recruit an inflammatory cell infiltrate dominated by macrophages and cause the accumulation of fluid, serum proteins, and more leukocytes, thus producing a visible lesion.
Antigen in the local tissues is internalized and processed by antigen-presenting cells and presented on MHC class II molecules. Antigen-specific TH1 cells that recognize the antigen:MHC complexes locally at the site of antigen injection release chemokines and cytokines that recruit macrophages and other leukocytes to the site. Antigen presentation by the newly recruited macrophages then amplifies the response. T cells can also affect local blood vessels through the release of TNF-α and lymphotoxin (LT), and stimulate the production of macrophages through the release of IL-3 and GM-CSF. TH1 cells activate macrophages through the release of IFN-γ and TNF-α, and kill macrophages and other sensitive cells through the cell-surface expression of the Fas ligand.
Contact Sensitivity to Poison Ivy
Fig. 14.21 The delayed-type hypersensitivity response is directed by chemokines and cytokines released by antigen-stimulated TH1 cells.
TNF-˜ and LT Chemokines lL-3/GM-CSFIFN-˛ Stimulate monocyte production by bone marrow stem cells Recruit macrophages and other leukocytes to site of antigen deposition Induces expression of vascular adhesion molecules. Activates macrophages, increasing release of infammatory mediators Cause local tissue destruction. Cooperate with IFN-˜to increase expression of adhesion molecules on local blood vessels Antigen is processed by tissue macrophages and stimulates TH1 cells cytokines cytotoxins chemokines TH1