Porth's Essentials of Pathophysiology, 4e

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Innate and Adaptive Immunity

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complement system, including enhanced inflammatory responses, increased phagocytosis, and destruction and clearance of the pathogen from the body, make it an inte- gral component of innate immunity and inflammation.

Adaptive Immunity The adaptive immune system is able to distinguish among different, even closely related, microbes and molecules and to “remember” the pathogen by quickly producing a heightened immune response on subse- quent encounters with the same agent. The components of the adaptive immune system are lymphocytes and their products. Foreign substances that elicit specific responses are called antigens. There are two types of adaptive immune responses: humoral and cell-mediated immunity. Humoral immu- nity is mediated by secreted molecules and is the prin- cipal defense against extracellular microbes and toxins. Cell-mediated immunity, or cellular immunity, is medi- ated by specific T lymphocytes and defends against intracellular microbes such as viruses. Antigens Before discussing the cells and responses inherent to adaptive immunity, it is important to understand the substances that elicit a response from the host. Antigens, also called immunogens, are substances foreign to the in three ways: by the classical pathway, an adaptive immune pathway which recognizes antibody bound to the surface of a microbe or other structure; by the lectin pathway, an innate pathway which uses a plasma protein called the mannose-binding ligand that binds to mannose residues on microbial glycoproteins or glycolipids; and by the alternative pathway, an innate pathway which recognizes certain microbial molecules. ■■ The effector responses of innate immunity involve viral destruction by natural killer (NK) cells, phagocytosis of microbes by neutrophils and monocytes, initiation of the inflammatory response, and recruitment of the complement system. ■■ Development of innate immunity and regulation of effector cells depends on the secretion of soluble mediators, such as opsonins, cytokines, and acute-phase proteins. Opsonins bind to and tag microorganisms for more efficient recognition by phagocytes. Cytokines released from activated leukocytes regulate the activity of other cells, amplify inflammation, stimulate the production of acute-phase proteins, and aid in the initiation of an adaptive immune response. ■■ The complement system, which is a primary effector system for both the innate and adaptive immune systems, consists of a group of proteins that are activated by microbes and promote inflammation and destruction of the microbes. Recognition of microbes by complement occurs

Role of Innate Immunity in Stimulating Adaptive Immunity

In addition to its role as a first-line defense in recog- nizing microbes and preventing infections, the innate immune response generates molecules that function as “second signals” together with antigens to activate the adaptive immune response. Full activation of antigen-specific B and T lymphocytes requires two signals. Antigen provides the first signal. Microbes, the response of the innate immune system to microbes, and host cells damaged by microbes all may provide the second sig- nal. This requirement for a second microbe-initiated sig- nal ensures that lymphocytes respond to microbes (the natural inducers of innate immunity) and not to harm- less noninfectious substances. For the purpose of induc- ing immunity through vaccination, adaptive immune responses may be induced by antigens without microbes. In such instances, the antigens have to be administered with substances called adjuvants that elicit the same adaptive immune reactions as microbes do. The second signals that are necessary for activa- tion of the adaptive immune system can be generated by antigen-presenting dendritic cells and macrophages or by activation of the complement system. Microbes that breach the epithelial barriers of the innate immune system stimulate dendritic cells and macrophages to produce two types of second signals that activate T lym- phocytes. First, the dendritic cells and macrophages express surface molecules called co-stimulators , which bind to receptors on naive T cells and function together with antigen recognition to activate T cells. Second, the dendritic cells and macrophages secrete cytokines that stimulate the differentiation of naive T cells into effector cells of cell-mediated adaptive immunity. Blood-borne microbes activate the complement system by the alter- native pathway. One of the proteins produced by the complement system becomes covalently attached to the microbe, producing a second signal for activation of B lymphocytes.

SUMMARY CONCEPTS

■■ Innate immunity consists of the physical, cellular, chemical, and molecular defenses that are ready for activation and mediate rapid initial protection against infectious agents. Epithelial cells of the skin and mucous membranes, which are the first line of defense, block the entry of infectious agents and secrete antimicrobial molecules that can effectively kill a wide variety of microbes.