Page 76 - Veterinary Immunology, 10th Edition

VetBooks.ir Products of Sentinel Cells

Macrophages, dendritic cells, and mast cells are activated when
PAMPs or DAMPs bind to their pattern-recognition receptors

(PRRs). As a result, they synthesize and secrete molecules that
trigger inflammation, inhibit microbial growth, and initiate the first
steps in adaptive immunity. Mediators released by the sentinel cells
diffuse to others nearby, where they bind to specific receptors and
trigger their responses. The cells of the immune system can

synthesize and secrete hundreds of different proteins that control
the immune responses in this way. These proteins are called
cytokines. Cytokines affect many different cell types, and cells

rarely secrete a single cytokine at a time. This generates a cytokine
network; a web of different signals transmitted among the cells of
the immune system mediated by complex mixtures of cytokines.

Cytokines

When exposed to infectious agents or PAMPs through PRRs,
sentinel cell signaling pathways activate the genes that result in the
synthesis and secretion of three major cytokines. These are called
tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), and IL-6.

TNF-α is produced very early in inflammation and is followed by
waves of IL-1 and then by IL-6. Activated sentinel cells also secrete
a mixture of small chemotactic proteins called chemokines. These
chemokines attract defensive cells to sites of microbial invasion. At

the same time, stimulated sentinel cells synthesize enzymes such as
nitric oxide synthase 2 (NOS2) that in turn generates nitric oxide
(NO), a powerful and lethal oxidant. They also make the enzyme
cyclooxygenase-2 (COX-2) that generates inflammatory lipids such

as the prostaglandins and leukotrienes. When these molecules reach
the brain and liver, they cause a fever and sickness behavior and
promote an acute-phase response (Chapter 7). If the sentinel cells
detect the presence of damaged or foreign DNA or RNA, such as

that from viruses, they will also secrete the antiviral type I
interferons, IFN-α and IFN-β (Chapter 27).

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