1. Mosby items and derived items © 2007, 2003 by Mosby, Inc.Slide 1 Chapter 21 Immune System

2. Mosby items and derived items © 2007, 2003 by Mosby, Inc.Slide 2 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

3. Mosby items and derived items © 2007, 2003 by Mosby, Inc.Slide 3 Organization of the Immune System  The immune system is continually at work patrolling and protecting the body  Identification of cells and other particles  Self markers—molecules on the surface of human cells that are unique to an individual, thus identifying the cell as “self” to the immune system  Non–self markers—molecules on the surface of foreign or abnormal cells or particles and identify the particle as “non–self” to the immune system  Self-tolerance—the ability of our immune system to attack abnormal or foreign cells but spare our own normal cells  Two major categories of immune mechanisms—innate immunity and adaptive immunity (Figure 21-1; Table 21-1)  Innate immunity provides a general, nonspecific defense against anything that is not “self”

4. Mosby items and derived items © 2007, 2003 by Mosby, Inc.Slide 4 Organization of the Immune System  Adaptive immunity acts as a specific defense against specific threatening agents  Primary cells for innate immunity—epithelial barrier cells, phagocytes (neutrophils, macrophages), and natural killer cells; chemicals used in innate immunity—complement and interferon  Primary types of cells for adaptive immunity—lymphocytes called T cells and B cells  Cytokines—any of several kinds of chemical released by cells to promote innate and adaptive immune responses (examples: interleukin, interferon, leukotriene)  Other chemicals (e.g., complement, other enzymes, and histamine) also play regulatory roles in immunity

5. Mosby items and derived items © 2007, 2003 by Mosby, Inc.Slide 5 Innate Immunity (Table 21-2)  Species resistance—genetic characteristics of an organism or species defends against pathogens  Mechanical and chemical barriers—first line of defense (Figure 21-2)  The internal environment of the body is protected by a barrier formed by skin and mucous membranes  Skin and mucous membranes provide additional immune mechanisms—sebum, mucus, enzymes, and hydrochloric acid in the stomach

6. Mosby items and derived items © 2007, 2003 by Mosby, Inc.Slide 6 Innate Immunity  Inflammation—second line of defense (Figure 21-3)  Inflammatory response—tissue damage elicits responses to counteract injury and promote normalcy Inflammation mediators include histamine, kinins, prostaglandins, and related compounds (Figure 21-4) Inflammation mediators include histamine, kinins, prostaglandins, and related compounds (Figure 21-4) Chemotactic factors—substances that attract white blood cells to the area in a process called chemotaxis Chemotactic factors—substances that attract white blood cells to the area in a process called chemotaxis Characteristic signs of inflammation—heat, redness, pain, and swelling Characteristic signs of inflammation—heat, redness, pain, and swelling Systemic inflammation—occurs from a body-wide inflammatory response Systemic inflammation—occurs from a body-wide inflammatory response

7. Mosby items and derived items © 2007, 2003 by Mosby, Inc.Slide 7 Innate Immunity  Inflammation—second line of defense (cont.)  Phagocytosis—ingestion and destruction of microorganisms or other small particles by phagocytes (Figure 21-7) Antigen-presenting cells (APCs)—phagocytes that ingest foreign particles, isolate protein segments (peptides), and display them as antigens on their surfaces to trigger an immune response when recognized by a specific (adaptive) immune cell Antigen-presenting cells (APCs)—phagocytes that ingest foreign particles, isolate protein segments (peptides), and display them as antigens on their surfaces to trigger an immune response when recognized by a specific (adaptive) immune cell Chemotaxis—chemical attraction of cells to the source of the chemical attractant (Figure 21-6) Chemotaxis—chemical attraction of cells to the source of the chemical attractant (Figure 21-6) Diapedesis—process by which immune cells squeeze through the wall of a blood vessel to get to the site of injury/infection (Figure 21-5) Diapedesis—process by which immune cells squeeze through the wall of a blood vessel to get to the site of injury/infection (Figure 21-5)

8. Mosby items and derived items © 2007, 2003 by Mosby, Inc.Slide 8 Innate Immunity  Phagocytosis (cont.) Neutrophil—most numerous type of phagocyte; usually first to arrive at site of injury; migrates out of bloodstream during diapedesis; forms pus Neutrophil—most numerous type of phagocyte; usually first to arrive at site of injury; migrates out of bloodstream during diapedesis; forms pus Macrophages (Table 21-3) Macrophages (Table 21-3)  Phagocytic monocytes grow larger after migrating from bloodstream  Dendritic cell (DC)—type of macrophage with long branches or extensions (Figure 21-8)  Examples are histiocytes in connective tissue, microglia in nervous system, and Kupffer cells in liver

9. Mosby items and derived items © 2007, 2003 by Mosby, Inc.Slide 9 Innate Immunity  Natural killer cells—lymphocytes that kill tumor cells and cells infected by viruses (Figure 21-9)  Method of recognizing abnormal or non–self 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  Interferon (INF)—protein synthesized and released into the 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 21-10)  Lyse cells when activated by either adaptive or innate mechanisms  Opsinization—mark cells for destruction by phagocytes  Variety of other immune responses

10. Mosby items and derived items © 2007, 2003 by Mosby, Inc.Slide 10 Overview of Adaptive Immunity  Adaptive immunity is part of the third line of defense consisting of lymphocytes—two different classes of a type of white blood cell (Figure 21-11)  Two classes of lymphocytes (Figure 21-12)—B lymphocytes (B cells) and T lymphocytes (T cells)  Subsets of lymphocytes are defined by the cluster designation (CD) surface markers that the cells carry, for example, CD4 and CD8 cells  Lymphocytes flow through the bloodstream, become distributed in tissues, and return to the bloodstream in a continuous recirculation  B-cell mechanisms—antibody-mediated immunity (humoral immunity); produce antibodies that attack pathogens (Figure 21-13)

11. Mosby items and derived items © 2007, 2003 by Mosby, Inc.Slide 11 Overview of Adaptive Immunity  T cells attack pathogens more directly—classified as cell-mediated immunity (cellular immunity)  Lymphocytes have protein markers on their surfaces that are named using the CD system  Activation of lymphocytes requires two stimuli: a specific antigen and activating chemicals (Figure 21-14)  Lymphocytes are densest where they develop— in bone marrow, thymus gland, lymph nodes, and spleen (Figure 21-15)

12. Mosby items and derived items © 2007, 2003 by Mosby, Inc.Slide 12 B Cells and Antibody-Mediated Immunity  B cells develop in two stages:  Pre-B cells develop by a few months of age  The second stage occurs in lymph nodes and spleen—activation of a naïve B cell after it binds a specific antigen  B cells serve as ancestors to antibody-secreting plasma cells  Antibodies—proteins (immunoglobulins) secreted by activated B cell (Figure 21-16)  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 21-17)  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 is different from the sequence synthesized by other clones

13. Mosby items and derived items © 2007, 2003 by Mosby, Inc.Slide 13 B Cells and Antibody-Mediated Immunity  Five classes of antibodies (Figure 21-18)— immunoglobulins M, G, A, E, and D  IgM—antibody that naïve B cells synthesize and insert into their own plasma membranes; it is 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  IgA—major class of antibody in the mucous membranes and in saliva and tears  IgE—small amount; produces harmful effects such as allergies  IgD—small amount in blood; precise function unknown  Antibody molecules produce antibody-mediated immunity (humoral immunity)—within plasma

14. Mosby items and derived items © 2007, 2003 by Mosby, Inc.Slide 14 B Cells and Antibody-Mediated Immunity  Antibodies resist disease first by recognizing foreign or abnormal substances (Figure 21-19)  Epitopes bind to an antibody molecule’s antigen-binding sites, forming an antigen-antibody complex that may produce several effects (Figure 21-20)  Complement—a component of blood plasma consisting of several protein compounds  Complement kills foreign cells by cytolysis or apoptosis (Figures 21-21 and 21-22)  Complement causes vasodilation, enhances phagocytosis, and other functions  Complement activity can also be initiated by innate immune mechanisms Formation by innate immunity is called the alternate pathway Formation by innate immunity is called the alternate pathway Complement protein 3—activated without antigen stimulation—produces full complement effect by binding to bacteria or viruses in presence of properdin Complement protein 3—activated without antigen stimulation—produces full complement effect by binding to bacteria or viruses in presence of properdin

15. Mosby items and derived items © 2007, 2003 by Mosby, Inc.Slide 15 B Cells and Antibody-Mediated Immunity  Primary and secondary responses (Figure 21-23)  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 wit the same antigen triggers a much quicker response; B memory cells rapidly divide, producing more plasma cells and thus more antibodies  Clonal selection theory (Figure 21-24)  The 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 according to the shape of antigen receptors on the lymphocyte’s plasma membrane

16. Mosby items and derived items © 2007, 2003 by Mosby, Inc.Slide 16 T Cells and Cell-Mediated Immunity  T cells—lymphocytes that go through the thymus gland before migrating to the lymph nodes and spleen  Pre-T cells develop into thymocytes while in thymus  Thymocytes stream into blood and are carried to T-dependent zones in spleen and lymph nodes  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 (presented by an APC) binds to its receptors, causing it to divide repeatedly to form a clone of identical T cells (Figure 21-25) Cells of the clone differentiate into effector T cells and memory T cells Cells of the clone differentiate into effector T cells and memory T cells Effector T cells go to site where antigen entered, bind to antigens, and begin their attack Effector T cells go to site where antigen entered, bind to antigens, and begin their attack

17. Mosby items and derived items © 2007, 2003 by Mosby, Inc.Slide 17 T Cells and Cell-Mediated Immunity  Cytotoxic T cells—T cells release lymphotoxin to kill cells (Figure 21-26)  Helper T cells (TH cells) —regulate the function of B cells, T cells, phagocytes, and other leukocytes (Figure 21-27)  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

18. Mosby items and derived items © 2007, 2003 by Mosby, Inc.Slide 18 Types of Adaptive Immunity (Table 21-4)  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  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—developed when immunity from another individual is transferred to an individual who was not previously immune; it is temporary but provides immediate protection

19. Mosby items and derived items © 2007, 2003 by Mosby, Inc.Slide 19 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 21-27)  B cells—antibody-mediated (humoral) immunity  T cells—cell-mediated (cellular) immunity  Adaptive immunity occurs in a series of stages (Figure 21-28)  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 21-29)

20. Mosby items and derived items © 2007, 2003 by Mosby, Inc.Slide 20 The Big Picture: Immune System and the Whole Body  Immune system regulated to some degree by the 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