Chronic Inflammatory Diseases

Recent studies suggest that regions of plump endothelial cells resembling HEVs appear along the vasculature in tertiary extralymphoid sites of chronic infection. These HEV-like regions, which appear to be sites of lymphocyte extravasation into the inflamed tissue, express several mucins (e.g., Gly-CAM-1, MAdCAM-1, and CD34) that are often displayed on normal HEVs. Several cytokines, notably IFN-y and TNF-a, that are associated with chronic inflammation may play a role in the induction of HEV-like regions along the vasculature.

These HEV-like regions have been observed in a number of chronic inflammatory diseases in humans, including i Proliferation i Production of IL-4 and IL-5

NK cell

CD4+ TH1 cell

NK cell

CD8+ TC cell

Interferon gamma (IFN-y)

CD4+ TH1 cell

CD8+ TC cell

Interferon gamma (IFN-y)

Cell Ifn Gamma Cd4 Cd8

CD4+ TH2 cell Macrophage Dendritic cell

NK cell

B cell

CD4+ TH2 cell Macrophage Dendritic cell

T Expression of class II MHC molecules T Microbicidal activity

T Expression of class II MHC molecules

NK cell

T Cytotoxic activity

FIGURE 15-15

Summary of pleiotropic activity of interferon gamma (IFN-7). The activation of macrophages induced by IFN-7 plays a critical role in chronic inflammation. This cytokine is secreted by TH1 cells,

B cell

T Differentiation T Antibody production (T IgG2a; i IgE and IgG1)

NK cells, and TC cells and acts on numerous cell types. [Adapted from Research News, 1993, Science 259:1693]

Treated

Untreated

Treated

Untreated

FIGURE 15-16

FIGURE 15-16

Biological activities of TNF-a. (a) A cancerous tumor in a mouse injected with endotoxin (left) shows hemorrhagic necrosis, unlike a tumor in an untreated mouse (right). Endotoxin induces the production of TNF-a, which then acts to destroy the tumor.

(b) Transgenic mouse (top) bearing a TNF-a transgene becomes anorectic and severely wasted. Normal mouse is shown on the bottom. [Part (a) from L. J. Old, 1988, Sci. Am. 258:59; part (b) from B. Beutler, 1993, Hosp. Prac. (April 15):45]

CLINICAL FOCUS

CLINICAL FOCUS

Leukocyte-Adhesion Deficiency (LAD) in Humans and Cattle

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