Macrophages activated to secrete Macrophages activated in the liver and TNF-˜ in the tissue spleen secrete TNF-˜ into the bloodstream
Increased release of plasma proteins into Systemic edema causing decreased blood tissue. Increased phagocyte and volume, hypoproteinemia, and neutropenia, lymphocyte migration into tissue. Increased followed by neutrophilia. Decreased blood platelet adhesion to blood vessel wall volume causes collapse of vessels
Phagocytosis of bacteria. Local vessel Disseminated intravascular coagulation occlusion. Plasma and cells drain to leading to wasting and multiple local lymph node organ failure
Removal of infection DeathAdaptive immunity mainly by TNF-α, IL-1β, and IL-6. These cytokines are termed endogenous pyrogens because they cause fever and derive from an endogenous source rather than from bacterial components such as LPS, which also induces fever and is an exogenous pyrogen. Endogenous pyrogens cause fever by inducing the synthesis of prostaglandin E2 by the enzyme cyclooxygenase-2, the expression of which is induced by these cytokines. Prostaglandin E2 then acts on the hypothalamus, resulting in an increase in both heat production from the catabolism of brown fat and heat retention from vasoconstriction, which decreases the loss of excess heat through the skin. Exogenous pyrogens are able to induce fever by promoting the production of the endogenous pyrogens
Induced innate responses to infection. 119
Fig. 3.32 The release of TNF-α by macrophages induces local protective effects, but TNF-α can be damaging when released systemically. The panels on the left show the causes and consequences of local release of TNF-α, and the panels on the right show the causes and consequences of systemic release. In both cases TNF-α acts on blood vessels, especially venules, to increase blood flow and vascular permeability to fluid, proteins, and cells, and to increase endothelial adhesiveness for leukocytes and platelets (center row). Local release thus allows an influx of fluid, cells, and proteins into the infected tissue, where they participate in host defense. Later, blood clots form in the small vessels (bottom left panel), preventing spread of infection via the blood, and the accumulated fluid and cells drain to regional lymph nodes, where an adaptive immune response is initiated. When there is a systemic infection, or sepsis, with bacteria that elicit TNF-α production, TNF-α is released into the blood by macrophages in the liver and spleen and acts in a similar way on all small blood vessels in the body (bottom right panel). The result is shock, disseminated intravascular coagulation with depletion of clotting factors, and consequent bleeding, multiple organ failure, and frequently death.
Fig. 3.33 The cytokines TNF-α, IL-1β, and IL-6 have a wide spectrum of biological activities that help to coordinate the body’s responses to infection. IL-1β, IL-6, and TNF-α activate hepatocytes to synthesize acute-phase proteins, and bone marrow endothelium to release neutrophils. The acute-phase proteins act as opsonins, whereas the disposal of opsonized pathogens is augmented by the enhanced recruitment of neutrophils from the bone marrow. IL-1β, IL-6, and TNF-α are also endogenous pyrogens, raising body temperature, which is believed to help in eliminating infections. A major effect of these cytokines is to act on the hypothalamus, altering the body’s temperature regulation, and on muscle and fat cells, altering energy mobilization to increase the body temperature. At higher temperatures, bacterial and viral replication is less efficient, whereas the adaptive immune response operates more efficiently.