8536d_ch01_001-0238/1/02 4: 25 PM Page 9 mac79 Mac 79: 45_BW: Goldsby et al./ Immunology 5e Overview of the Immune System CHAPTER 1 creased permeability of capillaries. A particular kinin, called sponses are intimately involved in activating the specific im bradykinin, also stimulates pain receptors in the skin. This mune response. Conversely, various soluble factors produced ffect probably serves a protective role, because pain ne y a specific immune response have been shown to augment mally causes an individual to protect the injured area the activity of these phagocytic cells. As an inflammatory re- an injured tissue also enable enzymes of the blood-clotting duced that attract cells of the soluble mediators are pro- Vasodilation and the increase in capillary permeability in sponse develops, for examp mmune system. The immune system to enter the tissue. These enzymes activate an enzyme response will, in turn, serve to regulate the intensity of the in cascade that results in the deposition of insoluble strands of flammatory response. Through the carefully regulated inter fibrin, which is the main component of a blood clot. The fib- play of adaptive and innate immunity, the two systems work rin strands wall off the injured area from the rest of the body together to eliminate a foreign invader. and serve t the spread of infection. Once the infammatory response has subsided and most The Adaptive Immune System Requires repair and regeneration of new tissue begins. Capillaries Cooperation Between Lymphocytes and grow into the fibrin of a blood clot. New connective tissue Antigen-Presenting Cells cells, called fibroblasts, replace the fibrin as the clot dissolves. An effective immune response involves two major groups of As fibroblasts and capillaries accumulate, scar tissue forms. cells: T lymphocytes and antigen-presenting cells. Lympho The inflammatory response is described in more detail in cytes are one of many types of white blood cells produced in Chapter 15. the bone marrow by the process of hematopoiesis(see Chap- ter 2) Lymphocytes leave the bone marrow, circulate in the blood and lymphatic systems, and reside in various lym Adaptive Immunity phoid organs. Because they produce and display antigen binding cell-surface receptors, lymphocytes mediate the Adaptive immunity is capable of recognizing and selectively defining immunologic attributes of specificity, diversity, eliminating specific foreign microorganisms and molecules memory, and self/nonself recognition. The two major popu (i.e, foreign antigens). Unlike innate immune responses, lations of lymphocytes--Blymphocytes(B cells)and Tlym- adaptive immune responses are not the same in all members phocytes(T cells)-are described briefly here and in greater of a species but are reactions to specific antigenic challenges. detail in later chapters Adaptive immunity displays four characteristic attributes: B LYMPHOCYTES n Diversity B lymphocytes mature within the bone marrow; when they ave it, each expresses a unique antigen-binding receptor on a Immunologic memory its membrane(Figure 1-5a). This antigen-binding or B-cell n Self/nonself recognition receptor is a membrane-bound antibody molecule. Anti bodies are glycoproteins that consist of two identical heavy The antigenic specificity of the immune system permits it to polypeptide chains and two identical light polypeptic distinguish subtle differences among antigens. Antibodies chains. Each heavy chain is joined with a light chain by disul can distinguish between two protein molecules that differ in fide bonds, and additional disulfide bonds hold the two pairs only a single amino acid. The immune system is capable of together. The amino-terminal ends of the pairs of heavy and generating tremendous diversity in its recognition molecules, light chains form a cleft within which antigen binds. When a llowing it to recognize billions of unique structures on for- naive B cell (one that has not previously encountered anti- eign antigens. Once the immune system has recognized and gen)first encounters the antigen that matches its membrane- responded to an antigen, it exhibits immunologic memory; bound antibody, the binding of the antigen to the antibody that is, a second encounter with the same antigen induces a causes the cell to divide rapidly; its progeny differentiate into heightened state of immune reactivity. Because of this memory B cells and effector B cells called plasma cells tribute, the immune system can confer life-long immunity to Memory B cells have a longer life span than naive cells, and many infectious agents after an initial encounter. Finally, the they express the same membrane-bound antibody as their immune system normally responds only to foreign antigens, parent B cell. Plasma cells produce the antibody in a form indicating that it is capable of self/nonself recognition. The that can be secreted and have little or no membrane-bound ability of the immune system to distinguish self from nonself antibody. Although plasma cells live for only a few days, they d respond only to nonself molecules is essential, for, as de- secrete enormous amounts of antibody during this time scribed below, the outcome of an inappropriate response to It has been estimated that a single plasma cell can secrete self molecules can be fatal more than 2000 molecules of antibody per second. Secreted o Adaptive immunity is not independent of innate immu- antibodies are the major effector molecules of humoral ity. The phagocytic cells crucial to nonspecific immune re- immunity.creased permeability of capillaries. A particular kinin, called bradykinin, also stimulates pain receptors in the skin. This effect probably serves a protective role, because pain nor￾mally causes an individual to protect the injured area. Vasodilation and the increase in capillary permeability in an injured tissue also enable enzymes of the blood-clotting system to enter the tissue. These enzymes activate an enzyme cascade that results in the deposition of insoluble strands of fibrin, which is the main component of a blood clot. The fib￾rin strands wall off the injured area from the rest of the body and serve to prevent the spread of infection. Once the inflammatory response has subsided and most of the debris has been cleared away by phagocytic cells, tissue repair and regeneration of new tissue begins. Capillaries grow into the fibrin of a blood clot. New connective tissue cells, called fibroblasts, replace the fibrin as the clot dissolves. As fibroblasts and capillaries accumulate, scar tissue forms. The inflammatory response is described in more detail in Chapter 15. Adaptive Immunity Adaptive immunity is capable of recognizing and selectively eliminating specific foreign microorganisms and molecules (i.e., foreign antigens). Unlike innate immune responses, adaptive immune responses are not the same in all members of a species but are reactions to specific antigenic challenges. Adaptive immunity displays four characteristic attributes: ■ Antigenic specificity ■ Diversity ■ Immunologic memory ■ Self/nonself recognition The antigenic specificity of the immune system permits it to distinguish subtle differences among antigens. Antibodies can distinguish between two protein molecules that differ in only a single amino acid. The immune system is capable of generating tremendous diversity in its recognition molecules, allowing it to recognize billions of unique structures on for￾eign antigens. Once the immune system has recognized and responded to an antigen, it exhibits immunologic memory; that is, a second encounter with the same antigen induces a heightened state of immune reactivity. Because of this at￾tribute, the immune system can confer life-long immunity to many infectious agents after an initial encounter. Finally, the immune system normally responds only to foreign antigens, indicating that it is capable of self/nonself recognition. The ability of the immune system to distinguish self from nonself and respond only to nonself molecules is essential, for, as de￾scribed below, the outcome of an inappropriate response to self molecules can be fatal. Adaptive immunity is not independent of innate immu￾nity. The phagocytic cells crucial to nonspecific immune re￾sponses are intimately involved in activating the specific im￾mune response. Conversely, various soluble factors produced by a specific immune response have been shown to augment the activity of these phagocytic cells. As an inflammatory re￾sponse develops, for example, soluble mediators are pro￾duced that attract cells of the immune system. The immune response will, in turn, serve to regulate the intensity of the in￾flammatory response. Through the carefully regulated inter￾play of adaptive and innate immunity, the two systems work together to eliminate a foreign invader. The Adaptive Immune System Requires Cooperation Between Lymphocytes and Antigen-Presenting Cells An effective immune response involves two major groups of cells: T lymphocytes and antigen-presenting cells. Lympho￾cytes are one of many types of white blood cells produced in the bone marrow by the process of hematopoiesis (see Chap￾ter 2). Lymphocytes leave the bone marrow, circulate in the blood and lymphatic systems, and reside in various lym￾phoid organs. Because they produce and display antigen￾binding cell-surface receptors, lymphocytes mediate the defining immunologic attributes of specificity, diversity, memory, and self/nonself recognition. The two major popu￾lations of lymphocytes—B lymphocytes (B cells) and T lym￾phocytes (T cells)—are described briefly here and in greater detail in later chapters. B LYMPHOCYTES B lymphocytes mature within the bone marrow; when they leave it, each expresses a unique antigen-binding receptor on its membrane (Figure 1-5a). This antigen-binding or B-cell receptor is a membrane-bound antibody molecule. Anti￾bodies are glycoproteins that consist of two identical heavy polypeptide chains and two identical light polypeptide chains. Each heavy chain is joined with a light chain by disul￾fide bonds, and additional disulfide bonds hold the two pairs together. The amino-terminal ends of the pairs of heavy and light chains form a cleft within which antigen binds. When a naive B cell (one that has not previously encountered anti￾gen) first encounters the antigen that matches its membrane￾bound antibody, the binding of the antigen to the antibody causes the cell to divide rapidly; its progeny differentiate into memory B cells and effector B cells called plasma cells. Memory B cells have a longer life span than naive cells, and they express the same membrane-bound antibody as their parent B cell. Plasma cells produce the antibody in a form that can be secreted and have little or no membrane-bound antibody. Although plasma cells live for only a few days, they secrete enormous amounts of antibody during this time. It has been estimated that a single plasma cell can secrete more than 2000 molecules of antibody per second. Secreted antibodies are the major effector molecules of humoral immunity. Overview of the Immune System CHAPTER 1 9 8536d_ch01_001-023 8/1/02 4:25 PM Page 9 mac79 Mac 79:45_BW:Goldsby et al. / Immunology 5e: