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“Adaptive Immunity”

Systemic manifestations of inflammation:- Include leukocytosis with a shift to the left, malaise, nausea and anorexia, Increased pulse and respiratory rate, and fever.  Leukoctosis results from the increased release of leukoytes form the bone marrow. An increase in the circulating number of one or more types of leukocytes may be found. Inflammatory responses are accompanied by the vaguely defined constitutional symptoms of malaise, nausea, anorexia, and fatigue. The causes of these systemic changes are poorly understood but are probably due to complement activation and the release of cytokines (soluble factors secreted by WBCs that act as intercellular messengers) from stimulated WBCs. Three of these cytokines, interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF), are important in causing the constitutional manifestations of inflammation, as well as inducing the production of fever. An increase in pulse and respiration follows the rise in metabolism as a result of an increase in body temperature.  Fever Pathophysiology 37 o The onset of fever is triggered by the release of cytokines. The most potent of these cytokines are IL-1, IL- 6, and TNF (released from mononuclear phagocytic cells). o These cytokines cause fever by their ability to initiate metabolic changes in the temperatureregulating center. The synthesis of prostaglandin E2 (PGE2) is the most critical metabolic change. PGE2 acts directly to increase the thermostatic set point. The hypothalamus then activates the sympathetic branch of the autonomic nervous system to stimulate increased muscle tone and shivering and decreased perspiration and blood flow to the periphery. Epinephrine released from the adrenal medulla increases the metabolic rate. The net result is fever. o With the physiologic thermostat fixed at a higherthan –normal temperature, the rate of heat production is increased until the body temperature reaches the new set point. As the set point is raised, the hypothalamus signals and increases in heat production and conservation to raise the body temperature to the new level.