Porth's Pathophysiology, 9e

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UNIT IV Infection, Inflammation, and Immunity

The adaptive immune system is the final line of defense against infection and is activated once the innate immune response initiates the inflammatory process. In contrast to innate immu- nity, the adaptive immune response is capable of targeting specific cells or organisms that it recognizes as foreign to the body through activation of various lymphocytes and their products, including antibodies. The lymphocytes involved in adaptive immunity have the unique ability to remember spe- cific pathogen and mount a heightened immune response dur- ing repeat exposures. Each exposure results in a more rapid and aggressive response. Substances present on the surface of pathogens or other foreign substances that elicit adaptive immune responses are called antigens . Adaptive immunity involves two distinct but interconnected mechanisms: humoral and cell-mediated responses. Humoral immunity is mediated by B-lymphocyte activation and subsequent antibody produc- tion. It is the primary defense against extracellular microbes and toxins. In contrast, cell-mediated immunity involves the activation of specific T lymphocytes (T-helper and T-cytotoxic lymphocytes), which are responsible for the body’s defense against intracellular microbes such as viruses. ADAPTIVE IMMUNITY •  The adaptive immune response involves a com- plex series of interactions between components of the immune system and the antigens of a foreign pathogen. It is able to distinguish between self and nonself, recognize and specifically react to large numbers of different microbes and pathogens, and remember the specific agents. •  Humoral immunity consists of protection provided by the B lymphocyte–derived plasma cells, which produce antibodies that travel in the blood and interact with circulating and cell surface antigens, whereas cell-mediated immunity provides pro- tection through cytotoxic T lymphocytes, which protect against virus-infected or cancer cells. Antigens Antigens, or immunogens , are substances or molecules that are foreign to the body but when introduced trigger the produc- tion of antibodies by B lymphocytes leading to the ultimate destruction of the invader. They are usually large macromol- ecules (>10,000 Da) such as proteins, polysaccharides, lipids, and free nucleic acids. Antigens are recognized by specific receptors present on the surface of lymphocytes and by the antibodies or immunoglobulins secreted in response to the antigen. Antigens can take the form of any foreign substance including bacteria, fungi, viruses, protozoa, parasites, and nonmicrobial agents such as plant pollens, insect venom, and transplanted organs. Key Points

IN SUMMARY The innate immune system is a complex system that works in an organized, rapid, yet nonspecific fashion as the body’s first line of defense against invasion. It is comprised of the epithelial cells of the skin and mucus membranes; phagocytic cells such as the neutrophils, macrophages, and NK cells; and a series of plasma proteins including cytokines, chemokines, and the proteins of the complement system. These defenses exist before the body encounters an invading microorganism and are activated independent of the adaptive humoral response. The epithelial cells of the skin and mucous membranes block the entry of infec- tious agents and secrete antimicrobial enzymes, proteins, and peptides in an attempt to prevent microorganisms from invading the internal environment. The phagocytes of the innate immune response engulf and digest infectious agents. They utilize PRRs, which are present on their membranes to recognize and bind broad patterns of molecules (PAMPs) shared by microbes and that are essential for their survival. TLRs are the most stud- ied of all PRRs and are expressed on many of the cells of the innate immune system. TLRs are involved in responses to widely divergent types of molecules that are commonly expressed by microbial but not mammalian cell types. Development of a healthy innate immune response is dependent not only upon the coordinated activity of the leuko- cytes but on the secretion of chemical mediators and soluble molecules, such as opsonins, cytokines, acute-phase proteins, and complement. Opsonins bind to and tag microorganisms for more efficient recognition by phagocytes. Activated leu- kocytes release cytokines that stimulate the migration of leu- kocytes to the site of inflammation, stimulate production of acute-phase proteins, and enhance phagocytosis. The complement system is a primary effector system that functions as part of both the innate and adaptive immune responses. It is comprised of a group of proteins that are activated by three distinct but convergent pathways: the classical, the lecithin, and the alternative pathways. The primary function of the complement system is the promo- tion of inflammation and destruction of the microbes.

ADAPTIVE IMMUNITY

After completing this section of the chapter, you should be able to meet the following objectives: •• Characterize the significance and function of major histocompatibility complex molecules. •• Compare and contrast the development and function of the T and B lymphocytes. •• Describe the function of cytokines involved in the adaptive immune response.