McKenna's Pharmacology for Nursing, 2e

C H A P T E R 1 5  Introduction to the immune response and inflammation 231

in the body: the kinin system , which is discussed here; the clotting cascade, which initiates blood clotting; and the plasminogen system, which initiates the dissolution of blood clots. The last two systems are discussed in Part VIII, Drugs acting on the cardiovascular system. Kinin system Hageman factor activates kallikrein, a substance found in the local tissues, which causes the precursor sub­ stance kininogen to be converted to bradykinin and other kinins. Bradykinin was the first kinin identified and remains the one that is best understood. Bradykinin causes local vasodilation, which brings more blood to the injured area and allows white blood cells to escape into the tissues. It also stimulates nerve endings to cause pain, which alerts the body to the injury. Bradykinin also causes the release of arachidonic acid from the cell membrane. Arachidonic acid causes the release of other substances called autacoids. These substances act like local hormones—they are released from cells, cause an effect in the immediate area and are then broken down. These autacoids include the following: • Prostaglandins, some of which augment the inflammatory reaction and some of which block it. • Leukotrienes, some of which can cause vasodilation and increased capillary permeability, and some of which can block the reactions. • Thromboxanes, which cause local vasoconstriction and facilitate platelet aggregation and blood coagulation. Histamine release While this series of Hageman factor-initiated events is proceeding, another locally mediated response is occur­ ring. Injury to a cell membrane causes the local release of histamine. Histamine causes vasodilation, which brings more blood and blood components to the area. It also alters capillary permeability, making it easier for neutro­ phils and blood chemicals to leave the bloodstream and enter the injured area. In addition, histamine stimulates pain perception. The vasodilation and changes in capil­ lary permeability bring neutrophils to the area to engulf and get rid of the invader or to remove the cell that has been injured. Chemotaxis Some leukotrienes activated by arachidonic acid have a property called chemotaxis , which is the ability to attract neutrophils and to stimulate them and other macrophages in the area to be very aggressive. Activation of the neutrophils and release of other chemicals into the area can lead to cell injury and destruction. When destroyed, the cell releases various lysosomal enzymes that dissolve or destroy cell membranes and cellular

also process antigens and present them to active lympho­ cytes for destruction. Macrophages can circulate in the blood stream or they can be fixed in specific tissues, such as the Kupffer cells in the liver, the cells in the alveoli of the respira­ tory tract, and the microglia in the central nervous system (CNS), GI, circulatory and lymph tissues. As active phagocytes, macrophages release chemicals that are necessary to elicit a strong inflammatory reaction. These cells also respond to chemical mediators released by other cells that are active in the inflammatory and immune responses to increase the intensity of a response and to facilitate the body’s reaction. Lymphoid tissues Lymphoid tissues that play an important part in the cellular defence system include the lymph nodes, spleen, thymus gland (a bipolar gland located in the middle of the chest, which becomes smaller with age), bone marrow and lymphoid tissue throughout the respiratory and GI tracts. The bone marrow and the thymus gland are important for creation of the cellular components of the MPS. The bone marrow has a role in the differenti­ ation of these cellular components. The thymus gland is responsible for the final differentiation of the T cells and for regulating the actions of the immune system. The lymph nodes and lymphoid tissue store concentrated populations of neutrophils, basophils, eosinophils and lymphocytes in areas of the body that facilitate their surveillance for and destruction of foreign proteins. Other cells travel through the cardiovascular and lymph systems to search for foreign proteins or to reach the sites of injury or pathogen invasion. ■■ The body has several defence mechanisms in place to protect it from injury or foreign invasion. ■■ Barrier defences include the skin, mucous membranes, normal flora and gastric acid. ■■ Cellular defences include blood cells such as the lymphocytes (T and B cells) and the myelocytes (neutrophils, eosinophils, basophils and macrophages). The inflammatory response The inflammatory response is the local reaction of the body to invasion or injury. Any insult to the body that injures cells or tissues sets off a series of events and chemical reactions. Nutritional: Immune: Acute inflammation Cell injury causes the activation of a chemical in the plasma called factor XII or Hageman factor . Hageman factor is responsible for activating at least three systems KEY POINTS