Page 188 - Veterinary Immunology, 10th Edition

VetBooks.ir Sickness Behavior

When an animal is invaded by pathogens, a response occurs
throughout the body—a response that we call sickness. The

subjective feelings of sickness (e.g., malaise, lassitude, fatigue, loss
of appetite, and muscle and joint pains, as well as a fever) are signs
of a systemic innate immune response. These reflect a change in the
body's priorities as it fights off the invaders. Microbial pathogen-
associated molecular patterns (PAMPs) acting through the pattern-

recognition receptors (PRRs) stimulate the production of
interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α).
All three of these cytokines signal to the brain using two pathways

(Fig. 7.1). One pathway acts through the sensory neurons that serve
damaged tissue. Sensory stimulation by IL-1β through the vagus
nerve can trigger signaling to the brain. (IL-1 will not trigger a fever
if the vagus nerve is cut.) Lipopolysaccharide (LPS) binding to toll-
like receptor 4 (TLR4) can also trigger these vagal signals. As a

result, they initiate fever, nausea, and other sickness responses in
the brain.

FIG. 7.1 Sickness behavior is part of the response of the body to
inflammatory stimuli. Multiple systemic effects are due to the four
major cytokines secreted by sentinel cells, mast cells, macrophages
and dendritic cells. The major sickness-inducing cytokines are IL-1,

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