Porth's Pathophysiology, 9e

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UNIT IV Infection, Inflammation, and Immunity

Key Points

INNATE IMMUNITY

INNATE IMMUNITY •  Innate immunity consists of physical, chemical, cellular, and molecular defenses that are ready for activation and mediate rapid, initial protection against infection. •  The effector responses of innate immunity involve the inflammatory process and phagocytosis by cells that express pattern recognition receptors (PRRs) that bind with broad patterns shared by groups of microbes but not present on mammalian cells. Toll-like receptors, a major type of PRR, are expressed on phagocytes and are potent activa- tors of innate immune system cells and molecules. Epithelial Barriers Physical, mechanical, and biochemical barriers against micro- bial invasion are found in all common portals of entry into the body, including the skin and respiratory, gastrointestinal, and urogenital tracts. The intact skin is by far the most formidable physical barrier available to infection because of its design. It is comprised of closely packed cells that are organized in mul- tiple layers that are continuously shed. In addition, a protective layer of protein, known as keratin, covers the skin. The skin has simple chemicals that create a nonspecific, salty, acidic environment and antibacterial proteins, such as the enzyme lysozyme, that inhibit the colonization of microorganisms and aid in their destruction. The complexity of the skin becomes evident in cases of contact dermatitis where increased suscep- tibility to cutaneous infection occurs as the result of abnor- malities of the innate immune response including defects in the epithelial layer itself and defects in both signaling and or expression of innate responses. 11 Sheets of tightly packed epithelial cells line and pro- tect the gastrointestinal, respiratory, and urogenital tracts and physically prevent microorganisms from entering the body. These cells destroy the invading organisms by secreting anti- microbial enzymes, proteins, and peptides. Specialized cells in these linings, such as the goblet cells in the gastrointestinal tract, secrete a viscous material comprised of high molecular weight glycoproteins known as mucins, which when hydrated form mucus . The mucins bind to pathogens, thereby trapping them and washing away potential invaders. In the lower respi- ratory tract, hairlike, mobile structures called cilia protrude through the epithelial cells and move microbes trapped in the mucus up the tracheobronchial tree and toward the throat. The physiologic responses of coughing and sneezing further aid in their removal from the body. Microorganisms that are trapped by mucus are then subjected to various chemical defenses present throughout the body. Lysozyme is a hydrolytic enzyme found in tears,

After completing this section of the chapter, you should be able to meet the following objectives: •• Understand the recognition systems for pathogens in innate immunity. •• Describe the functions of the various cytokines involved in innate immunity. •• Define the role of the complement system in immu- nity and inflammation. The innate immune system is comprised of two separate but interrelated lines of defense: the epithelial layer, which acts as a physical barrier to invading substances and organ- isms, and the inflammatory response. The innate immune response utilizes the body’s natural epithelial barriers along with phagocytic cells (mainly neutrophils and mac- rophages), natural killer (NK) cells, and several plasma proteins, including kinins, clotting factors, and those of the complement system, to maintain internal homeostasis. The innate immune response relies on the body’s ability to distinguish evolutionarily conserved structures on patho- gens known as PAMPs from structures on human cells. 3 The response of the innate immune system is rapid, usu- ally within minutes to hours, and prevents the establishment of infection and deeper tissue penetration of microorgan- isms. The innate immune response is usually very effective against most pathogens. However, when the innate response is overwhelmed, adaptive immune responses become acti- vated as the final line of defense against invading organisms. Innate immune mechanisms are always present in the body before an encounter with an infectious agent and are rap- idly activated by microorganisms and foreign substances. Therefore, the body’s defenses are in full swing before the development of the adaptive immune response. The innate immune system also interacts with and directs adaptive immune responses. Under normal conditions, the innate immune response is essential to the continued health and well-being of the body. However, during times of hyperresponsiveness or hypore- sponsiveness, the innate immune system plays a role in the pathogenesis of disease. One of the main functions of the innate immune system is the initiation of the inflammatory response, which involves the activation of a complex cas- cade of events and chemical mediators. As part of the innate immune response, inflammation plays a key role in the patho- genesis of many common pathophysiologic states includ- ing atherosclerosis and coronary artery disease, bronchial asthma, non–insulin-dependent diabetes mellitus (NIDDM), rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus.