Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. Chapter 24: Immune System Anatomy & Physiology

Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. Introduction The immune system protects against assaults on the body  External assaults include microorganisms—protozoans, bacteria, and viruses  Internal assaults—abnormal cells reproduce and form tumors that may become cancerous and spread 2

Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. Organization of the Immune System Immune system continually patrols and protects the body Identification of cells and other particles  Markers, or antigens, are unique molecules recognized by the immune system  Self markers—molecules on the surface of our cells that are unique to an individual, thus identifying the cell as “self” to the immune system  Nonself markers—molecules on the surface of foreign or abnormal cells or particles that identify the particle as “nonself” to the immune system  Self-tolerance—the ability of our immune system to attack abnormal or foreign cells but spare our own normal cells 3

Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. Organization of the Immune System Two major categories of immune mechanisms— innate immunity and adaptive immunity (Figure 24-1; Table 24-1)  Innate immunity provides a general, nonspecific defense against anything that is not “self”  Adaptive immunity acts as a specific defense against specific threatening agents  Primary cells of innate immunity—epithelial barrier cells, phagocytes (neutrophils, macrophages, DCs), and natural killer cells; chemicals used in innate immunity— complement and interferon 4

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Organization of the Immune System Two major categories of immune mechanisms (cont)  Primary cells of adaptive immunity— lymphocytes called T cells and B cells  Cytokines—chemicals released from cells to promote or trigger innate and adaptive immune responses (e.g., interleukin, interferon, leukotriene)  Other chemicals (e.g., complement, other enzymes, histamine) also play regulatory roles in immunity 6

Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. Innate Immunity (Table 24-2) Species resistance—genetic characteristics of an organism or species defend against pathogens Mechanical and chemical barriers—first line of defense (Figure 24-2)  Internal environment of the body is protected by a barrier formed by the skin and the mucous membranes  Skin and mucous membranes provide additional immune mechanisms—sebum, mucus, enzymes, and hydrochloric acid in the stomach 7

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Innate Immunity Inflammation and fever—second line of defense (Figure 24-3)  Inflammatory response—tissue damage elicits responses to counteract injury and promote normalcy Inflammation mediators include histamine, kinins, prostaglandins, and related compounds (Figure 24-4) Chemotactic factors—substances that attract white blood cells to area of injury in a process called chemotaxis (Figure 24-6) Characteristic signs of inflammation—heat, redness, pain, and swelling Systemic inflammation—occurs from a bodywide inflammatory response 9

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Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. Innate Immunity Inflammation and fever (cont)  Fever—abnormally high body temperature triggered by inflammation mediators Triggered in SIRS (systemic inflammatory response syndrome) and other events such as viral infections, tumors, allergies 13

Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. Innate Immunity  Fever (cont) Pyrogens released from damaged tissues (endogenous) or introduced into the body (exogenous)  Promote prostaglandin (PG) production  PGs reset the hypothalamic “thermostat” to a higher temperature  Aspirin and other COX inhibitors interfere with PG production Fever is thought to increase immune function and inhibit pathogens 14

Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. Innate Immunity Phagocytosis—ingestion and destruction of microorganisms or other small particles by phagocytes (Figure 24-7)  Phagocytes—many types capable of phagocytosis (Table 24-3)  Antigen-presenting cells (APCs)—phagocytes that ingest foreign particles, isolate protein segments (peptides), and display them as antigens on their surface to trigger an immune response when recognized by a specific (adaptive) immune cell Neutrophil—most numerous phagocyte; usually first to arrive at site of injury; migrates out of bloodstream during diapedesis; form pus 15

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Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. Innate Immunity  Antigen-presenting cells (cont) Diapedesis—process by which immune cells squeeze through the wall of a blood vessel to get to the site of injury or infection (Figure 24-5) Macrophage—large phagocytic monocyte cells that grow to several times original size after migrating out of bloodstream; important APCs Dendritic cell (DC)—type of APC with long branches or extensions (Figure 24-8) Phagocytes often identified by location— histiocytes in connective tissue, microglia in nervous system, and Kupffer cells in liver 17

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Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. Innate Immunity Natural killer (NK) cells—lymphocytes that kill tumor cells and cells infected by viruses (Figure 24-9)  Method of recognizing abnormal or nonself cells—target cell is killed if killer- inhibiting receptor on NK cell does not bind to a proper MHC surface protein  Method of killing cells—lysing cells by damaging plasma membranes 20

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Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. Innate Immunity Interferon (IFN)—protein synthesized and released into circulation by certain cells if invaded by viruses to signal other nearby cells to enter a protective antiviral state Complement—group of enzymes that produce a cascade of reactions resulting in a variety of immune responses (Figure 24-10)  Lyse cells when activated by either adaptive or innate mechanisms  Opsonization—process that marks cells for destruction by phagocytes  Variety of other immune responses (Figure 24-10) 22

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Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. Innate Immunity Toll-like receptors (TLRs)—pattern- recognition receptors in the membranes of host cells; when triggered, TLRs stimulate many different kinds of innate immune responses 24

Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. Overview of Adaptive Immunity Adaptive immunity  Part of the third line of defense consisting of lymphocytes  Two different classes of a white blood cell (lymphocyte) involved (Figure ) 25

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Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. Overview of Adaptive Immunity Classes of lymphocytes (Figure )—B lymphocytes (B cells) and T lymphocytes (T cells)  B-cell mechanisms—antibody- mediated immunity (humoral immunity); produce antibodies that attack pathogens (Figure 24-13)  T cell mechanisms—attack pathogens more directly—classified as cell- mediated immunity (cellular immunity) 27

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Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. Overview of Adaptive Immunity Classes of lymphocytes (cont)  Lymphocytes have protein markers on their surfaces Surface markers named using the CD (cluster of differentiation) system Examples include CD4 and CD8 cells, clinically important in diagnosing AIDS  Activation of lymphocytes requires two stimuli: a specific antigen and activating chemicals (Figure 24-14) 30

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Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. Overview of Adaptive Immunity Classes of lymphocytes (cont)  Lymphocytes are densest where they develop—in bone marrow, thymus gland, lymph nodes, and spleen (Figure 24-15)  Lymphocytes flow through the bloodstream, become distributed in tissues, and return to the bloodstream in a continuous recirculation 32

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Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. B Cells and Antibody-Mediated Immunity Development and activation of B cells  Development occurs in two stages (Figure 24-16) Pre–B cells develop in red bone marrow (prenatal, in the yolk sac and fetal liver) Second stage occurs in lymph nodes and spleen— activation of a naïve B cell after it binds to a specific antigenic. B cells divide repeatedly—serve as ancestors to antibody-secreting plasma cells  Some of the clone cells differentiate to form B cells or plasma cells  Others remain in lymphatic tissue and become memory B cells 34

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Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. B Cells and Antibody-Mediated Immunity Antibodies—proteins (immunoglobulins) secreted by activated B cell (Figure 24-16)  Structure of antibody molecules An antibody molecule consists of two heavy and two light polypeptide chains Each molecule has two antigen-binding sites and two complement-binding sites (Figure 24-17) 36

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Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. B Cells and Antibody-Mediated Immunity Antibodies (cont)  Diversity of antibodies Babies are born with different clones of B cells in bone marrow, lymph nodes, and spleen Cells of the clone synthesize a specific antibody with a sequence of amino acids in its variable region that differs from the sequence synthesized by other clones 38

Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. B Cells and Antibody-Mediated Immunity Antibodies (cont)  Classes of antibodies (Figure 24-18)— immunoglobulins M, G, A, E, and D IgM—antibody that naïve B cells synthesize and insert into their own plasma membranes; the predominant class produced after initial contact with an antigen IgG—makes up 75% of antibodies in the blood; predominant antibody of the secondary antibody response 39

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Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. B Cells and Antibody-Mediated Immunity  Classes of antibodies (cont) IgA—major class of antibody in the mucous membranes, in saliva and tears (also found in plasma) IgE—small amount; produces harmful effects such as allergies IgD—small amount in blood; precise function unknown 41

Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. B Cells and Antibody-Mediated Immunity Antibodies (cont)  Functions of antibodies (Figure 24-19) Antigen-antibody reactions  Transforms toxic antigens into harmless substances  Agglutinates antigens to make disposal by phagocytes more rapid  Alters the shape of antigen molecule to expose complement-binding sites (Figure 24-20) 42

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Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. B Cells and Antibody-Mediated Immunity  Functions of antibodies (cont) Complement—a component of blood plasma consisting of several protein compounds (inactive enzymes)  Antibodies can activate complement after binding to an antigen by exposing complement-binding sites that trigger a cascade of linked chemical reactions to produce a variety of immune effects 45

Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. B Cells and Antibody-Mediated Immunity  Antibodies can activate complement after binding (cont) Membrane attack complex (MAC)— complement cascade can form doughnut- shaped structures that produce a hole in a foreign cell’s membrane, causing cytolysis (cell rupture) (Figures and 24-22) Complement can also cause vasodilation, enhances phagocytosis, and has other effects 46

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Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. B Cells and Antibody-Mediated Immunity Complement (cont)  Complement activity can also be initiated by innate immune mechanisms Complement protein 3 (C3)—activated without antigen stimulation—produces full complement effect by binding to bacteria or viruses in presence of properdin Complement activation by innate immunity is called the alternate pathway 49

Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. B Cells and Antibody-Mediated Immunity  Functions of antibodies (cont) Primary and secondary responses (Figure 24-23)  Primary response—initial encounter with a specific antigen triggers the formation and release of specific antibodies that reaches its peak in a few days  Secondary response—a later encounter with the same antigen triggers a much quicker response; B memory cells rapidly divide, producing more plasma cells and thus more antibodies 50

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Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. B Cells and Antibody-Mediated Immunity Clonal selection theory (Figure 24-24)  Two basic tenets Body contains many diverse clones of cells, each committed by its genes to synthesize a different antibody When an antigen enters the body, it selects the clone whose cells are synthesizing its antibody and stimulates them to proliferate and create more antibody  The clones selected by antigens consist of lymphocytes and are selected by the shape of antigen receptors on the lymphocyte’s plasma membrane 52

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Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. T Cells and Cell-Mediated Immunity Development of T cells  T Cells are lymphocytes that go through the thymus gland before migrating to the lymph nodes and spleen  Pre–T cells develop into thymocytes while in the thymus  Thymocytes stream into the blood and are carried to the T-dependent zones in the spleen and the lymph nodes 54

Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. T Cells and Cell-Mediated Immunity Activation of T cells  T cells display antigen receptors on their surface membranes that are similar to antibodies  A T cell is activated when an antigen (in an infected cell or presented by an APC) binds to its receptors (at an IS), causing the T cell to divide repeatedly to form a clone of identical T cells (Figure 24-25) Cells of the clone differentiate into effector T cells and memory T cells Effector T cells go to the site where the antigen entered, bind to antigens, and begin their attack Memory T cells remain in bone marrow until needed later to produce more effector T cells and memory T cells 55

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Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. T Cells and Cell-Mediated Immunity Functions of T cells  Cytotoxic T cells—T cells release lymphotoxin to kill cells (Figure 24-26)  Helper T cells (T H cells)—regulate the function of B cells, T cells, phagocytes, and other leukocytes (Figure 24-27)  Suppressor T cells—regulatory T cells that suppress lymphocyte function, thus regulating immunity and promoting self tolerance  T cells function to produce cell-mediated immunity and help to regulate adaptive immunity in general 57

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Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. Types of Adaptive Immunity (Table 24-4) Innate immunity (inborn or inherited immunity)— genetic mechanisms put innate immune mechanisms in place during development in the womb Adaptive or acquired immunity; resistance developed after birth; two types:  Natural immunity results from nondeliberate exposure to antigens  Artificial immunity results from deliberate exposure to antigens, called immunization 60

Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. Types of Adaptive Immunity Natural and artificial immunity may be active or passive  Active immunity—when the immune system responds to a harmful agent regardless of whether it was natural or artificial; lasts longer than passive  Passive immunity—immunity developed in another individual is transferred to an individual who was not previously immune; it is temporary but provides immediate protection 61

Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. Summary of Adaptive Immunity Adaptive immunity is specific immunity—targeting specific antigens Adaptive immunity involves two classes of lymphocyte: B cells and T cells (Figure 24-27)  B cells—antibody-mediated (humoral) immunity  T cells—cell-mediated (cellular) immunity 62

Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. Summary of Adaptive Immunity Adaptive immunity occurs in a series of stages (Figure 24-28)  Recognition of antigen  Activation of lymphocytes  Effector phase (immune attack)  Decline of antigen causes lymphocyte death (homeostatic balance)  Memory cells remain for later response if needed B cells and T cells work together in a coordinated system of adaptive immunity (Figure 24-29) 63

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Mosby items and derived items © 2013, 2010, 2007, 2003 by Mosby, Inc., an affiliate of Elsevier Inc. The Big Picture: Immune System and The Whole Body Immune system regulated to some degree by nervous and endocrine systems Agents of the immune system include blood cells, skin cells, mucosal cells, brain cells, liver cells, and other types of cells and their secretions 66