The Immune System. In innate immunity, recognition and response rely on shared traits of pathogens

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1 hapter 43 The Immune System PowerPoint Lectures for Biology, Eighth Edition Overview: Reconnaissance, Recognition, and Response Barriers help an animal to defend itself from the many dangerous pathogens it may encounter The immune system recognizes foreign bodies and responds with the production of immune cells and proteins Two major kinds of defense: innate immunity and acquired immunity Lectures by hris Romero, updated by Erin Barley with contributions from Joan Sharp and Janette Lewis opyright 2008 Pearson Education, Inc., publishing as Pearson Benjamin ummings opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 2 of 106 How do immune cells of animals recognize foreign cells? 1.5 µm The Immune System Innate immunity is present before any exposure to pathogens and is effective from the time of birth It involves nonspecific responses to pathogens Innate immunity consists of external barriers plus internal cellular and chemical defenses Acquired immunity, or adaptive immunity, develops after exposure to agents such as microbes, toxins, or other foreign substances It involves a very specific response to pathogens opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 3 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 4 of 106 Overview of animal immunity INNATE IMMUNITY (all animals) Recognition of traits shared by broad ranges of pathogens, using a small set of receptors Rapid response ADAPTIVE IMMUNITY (vertebrates only) Recognition of traits specific to particular pathogens, using a vast array of receptors Slower response Barrier defenses: Skin Mucous membranes Secretions Pathogens (such as bacteria, fungi, and viruses) Internal defenses: Phagocytic cells Natural killer cells Antimicrobial proteins Inflammatory response Humoral response: Antibodies defend against infection in body fluids. ell-mediated response: ytotoxic cells defend against infection in body cells. oncept 43.1: In innate immunity, recognition and response rely on shared traits of pathogens In innate immunity, recognition and response rely on shared traits of pathogens Both invertebrates and vertebrates depend on innate immunity to fight infection Vertebrates also develop acquired immune defenses opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 6 of 106 1

2 Innate Immunity Innate immunity of invertebrates In insects, an exoskeleton made of chitin forms the first barrier to pathogens The digestive system is protected by low ph and lysozyme, an enzyme that digests microbial cell walls Hemocytes circulate within hemolymph and carry out phagocytosis, the ingestion and digestion of foreign substances including bacteria Phagocytosis Microbes PHAGOYTI ELL Vacuole Lysosome containing enzymes opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 7 of 106 Innate Immunity of Vertebrates The immune system of mammals is the best understood of the vertebrates Innate defenses include barrier defenses, phagocytosis antimicrobial peptides Additional defenses are unique to vertebrates: the inflammatory response natural killer cells Innate Immunity Barrier defenses include the skin and mucous membranes of the respiratory, urinary, and reproductive tracts Mucus traps and allows for the removal of microbes Many body fluids including saliva, mucus, and tears are hostile to microbes The low ph of skin and the digestive system prevents growth of microbes ilia: beat rhythmically, move pathogens out opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 9 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 10 of 106 ilia of ells in Trachea 10μm Innate Immunity: Phagocytosis Phagocytosis ellular innate defenses include white blood cells (leukocytes) engulf pathogens in the body Groups of pathogens are recognized by leukocytes by TLR, Toll-like receptors Figure 43.3 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 11 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 12 of 106 2

3 TLR signaling EXTRAELLULAR FLUID WHITE BLOOD ELL VESILE pg DNA ds RNA Helper protein Lipopolysaccharide TLR9 TLR3 TLR4 Flagellin TLR5 Inflammatory responses Innate Immunity: Phagocytosis A white blood cell engulfs a microbe, then fuses with a lysosome to destroy the microbe There are different types of phagocytic WBs: Neutrophils engulf and destroy microbes Macrophages are part of the lymphatic system and are found throughout the body Eosinophils discharge destructive enzymes Dendritic cells stimulate development of acquired immunity opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 13 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 14 of 106 InnateImmunity The lymphatic system returns lost fluid and proteins (lymph) from the tissues to the blood lymph nodes filter lymph contain white blood cells that attack viruses and bacteria include: tonsils, adenoids, spleen, appendix and portions of the small intestine The human lymphatic system: Innate Immunity Adenoid Tonsil Lymph nodes Spleen Peyer s patches (small intestine) Appendix Tissue cells Interstitial fluid Lymphatic vessel Blood capillary Lymphatic vessels Lymph node Masses of defensive cells opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 15 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 16 of 106 Innate Immunity Inflammatory Responses Following an injury, mast cells release histamine, which promotes changes in blood vessels; this is part of the inflammatory response These changes increase local blood supply and allow more phagocytes and antimicrobial proteins to enter tissues Pus, a fluid rich in white blood cells, dead microbes, and cell debris, accumulates at the site of inflammation Major events in a local inflammatory response Pathogen Mast cell hemical signals Splinter Macrophage apillary Red blood cells Phagocytic cell opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 17 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 18 of 106 3

4 Major events in a local inflammatory response Major events in a local inflammatory response Pathogen Splinter Pathogen Splinter Mast cell hemical signals Macrophage Fluid Mast cell hemical signals Macrophage Fluid apillary apillary Phagocytosis Red blood cells Phagocytic cell Red blood cells Phagocytic cell opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 19 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 20 of 106 Innate Immunity Antimicrobial Peptides and Proteins Peptides and proteins function in innate defense by attacking microbes directly or impeding their reproduction Interferon proteins provide innate defense against viruses and help activate macrophages About 30 proteins make up the complement system, which causes lysis of invading cells and helps trigger inflammation Innate Immunity Inflammation Inflammation can be either local or systemic (throughout the body) Fever is a systemic inflammatory response triggered by pyrogens released by macrophages, and toxins from pathogens Septic shock is a life-threatening condition caused by an overwhelming inflammatory response opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 21 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 22 of 106 Innate Immunity Natural killer cells All cells in the body (except red blood cells) have a class 1 MH protein on their surface ancerous or virus-infected cells no longer express this protein; natural killer (NK) cells attack these damaged cells and trigger apoptosis Innate Immune System Evasion by Pathogens Some pathogens avoid destruction by modifying their surface to prevent recognition or by resisting breakdown following phagocytosis Tuberculosis (TB) is one such disease and kills more than a million people a year opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 23 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 24 of 106 4

5 oncept 43.2: In acquired immunity, lymphocyte receptors provide pathogen-specific recognition In acquired immunity, lymphocyte receptors provide pathogen-specific recognition: the second line of defense White blood cells called lymphocytes recognize and respond to antigens, foreign s Lymphocytes that mature in the thymus above the heart are called T cells, and those that mature in bone marrow are called B cells Lymphocytes and Acquired Immunity Lymphocytes contribute to immunological memory, an enhanced response to a foreign encountered previously ytokines are secreted by macrophages and dendritic cells to recruit and activate lymphocytes opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 25 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 26 of 106 Acquired Immunity: An Overview Overview of acquired immunity B cells and T cells have receptor proteins that can bind to foreign s Each individual lymphocyte is specialized to recognize a specific type of An antigen is any foreign to which a lymphocyte responds A single B cell or T cell has about 100,000 identical antigen receptors Antigen receptors on lymphocytes T cell opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 27 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 28 of 106 Antigenbindinbinding site binding Antigen- Antigen- site site Disulfide bridge Variable regions V V onstant regions Light chain Transmembrane region Plasma membrane Heavy chains α chain β chain Disulfide bridge B cell ytoplasm of B cell ytoplasm of T cell (a) B cell receptor (b) T cell receptor Antigenbinding site Antigenbinding site Antigenbinding site Disulfide bridge Variable regions Variable regions V V Light chain onstant regions Transmembrane region onstant regions Transmembrane region Heavy chains Plasma membrane Plasma membrane α chain β chain Disulfide bridge B cell ytoplasm of B cell ytoplasm of T cell T cell (a) B cell receptor (b) T cell receptor Slide 29 of 106 Slide 30 of 106 5

6 Acquired Immunity: An Overview Antigen receptors All antigen receptors on a single lymphocyte recognize the same epitope, or antigenic determinant, a small accessible portion of an an antigen Epitopes (antigenic determinants) Antigen-binding sites Antigenbinding sites Antibody A Antigen Antibody Epitopes (antigenic determinants) Antibody B opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 31 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 32 of 106 The Antigen Receptors of B ells and T ells B cell receptors bind to specific, intact antigens The B cell receptor consists of two identical heavy chains and two identical light chains The tips of the chains form a constant () region, and each chain contains a variable (V) region, so named because its amino acid sequence varies extensively from one B cell to another The Antigen Receptors of B ells and T ells Activated B cells When a B cell receptor binds to an antigen the cell becomes activated and give rise to plasma cells, which secrete proteins called antibodies or immunoglobulins Secreted antibodies, or immunoglobulins, are structurally similar to B cell receptors but lack transmembrane regions that anchor receptors in the plasma membrane opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 33 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 34 of 106 The Antigen Receptors of B ells and T ells Each T cell receptor consists of two different polypeptide chains The tips of the chain form a variable (V) region; the rest is a constant () region T cells can bind to an antigen that is free or on the surface of a pathogen The Antigen Receptors of B ells and T ells T cells bind to antigen fragments presented on a host cell These antigen fragments are bound to cellsurface proteins called MH s MH s are so named because they are encoded by a family of genes called the major histocompatibility complex opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 35 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 36 of 106 6

7 The Antigen Receptors of B ells and T ells Antigen presentation by an MH The role of MH s In infected cells, MH s bind and transport antigen fragments to the cell surface, a process called antigen presentation A nearby T cell can then detect the antigen fragment displayed on the cell s surface Depending on their source, peptide antigens are handled by different classes of MH s lass I MH Antigen Plasma membrane of infected cell Top view: binding surface exposed to antigen receptors Antigen opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 37 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 38 of 106 The Antigen Receptors of B ells and T ells lasses of MH s lass I MH s are found on almost all nucleated cells of the body They display peptide antigens to cytotoxic T cells lass II MH s are located mainly on dendritic cells, macrophages, and B cells Dendritic cells, macrophages, and B cells are antigen-presenting cells that display antigens to cytotoxic T cells and helper T cells The interaction of T cells with antigen-presenting cells Infected cell Antigen fragment lass I MH T cell receptor (a) Antigen associates with MH T cell recognizes combination Microbe Antigenpresenting cell Antigen fragment lass II MH T cell receptor ytotoxic T cell (b) Helper T cell 2 1 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 39 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 40 of 106 Properties of Acquired Immunity The acquired immune system has three important properties: Receptor diversity A lack of reactivity against host cells: Selftolerance Immunological memory Properties of Acquired Immunity Receptor diversity Differences in the variable region account for specificity of antigen receptors The immunoglobulin (Ig) gene encodes one chain of the B cell receptor Many different chains can be produced from the same Ig chain gene by rearrangement of the DNA Rearranged DNA is transcribed and translated and the antigen receptor formed opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 41 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 42 of 106 7

8 Immunoglobulin (antibody) gene rearrangement DNA of undifferentiated B cell V 37 V 38 V 39 V 40 J 1 J 2 J 3 J 4 J 5 Intron DNA of differentiated B cell V 37 V 38 V 39 J 5 Intron pre-mrna mrna ap V 39 J 5 V 39 J 5 1 DNA deleted between randomly selected V and J segments Functional gene 2 Transcription Intron 3 RNA processing Poly-A tail 4 Translation V V B cell receptor V V Properties of Acquired Immunity Self-tolerance Antigen receptors are generated by random rearrangement of DNA As lymphocytes mature in bone marrow or the thymus, they are tested for self-reactivity Lymphocytes with receptors specific for the body s own s are destroyed by apoptosis, or rendered nonfunctional Light-chain polypeptide V Variable onstant region region B cell opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 43 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 44 of 106 Properties of Acquired Immunity Immunological memory In the body there are few lymphocytes with antigen receptors for any particular epitope The binding of a mature lymphocyte to an antigen induces the lymphocyte to divide rapidly This proliferation of lymphocytes is called clonal selection Two types of clones are produced: shortlived activated effector cells and long-lived memory cells opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 45 of 106 lonal selection of B cells B cells that differ in antigen specificity Antibody s Antigen s Antigen receptor lone of memory cells lone of plasma cells opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 46 of 106 Immunological Memory The first exposure to a specific antigen represents the primary immune response During this time, effector B cells called plasma cells are generated, and T cells are activated to their effector forms Numerous long-lived memory B and T cells form In the secondary immune response, memory cells facilitate a faster, more efficient response Animation: Role of B ells Right-click slide / select Play opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 47 of Pearson Education, Inc. 8

9 The specificity of immunological memory Primary immune response to antigen A produces antibodies to A. Antibody concentration (arbitrary units) Exposure to antigen A Secondary immune response to antigen A produces antibodies to A; primary immune response to antigen B produces antibodies to B. Antibodies to A Antibodies to B Exposure to antigens A and B Time (days) opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 49 of 106 oncept 43.3: Acquired immunity defends against infection of body cells and fluids Acquired immunity has two branches: the humoral immune response and the cellmediated immune response Humoral immune response involves activation and clonal selection of B cells, resulting in production of secreted antibodies ell-mediated immune response involves activation and clonal selection of cytotoxic T cells Helper T cells aid both responses opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 50 of 106 Humoral (antibody-mediated) immune response ell-mediated immune response Humoral (antibody-mediated) immune response Antigen (1st exposure) Engulfed by Antigenpresenting cell Key Stimulates Gives rise to Key Stimulates Gives rise to Antigen (1st exposure) Engulfed by Antigenpresenting cell B cell Helper T cell ytotoxic T cell B cell Helper T cell Memory Helper T cells Memory Helper T cells Plasma cells Antigen (2nd exposure) Memory Memory B cells ytotoxic T cells Active ytotoxic T cells Plasma cells Antigen (2nd exposure) Memory B cells Secreted antibodies Defend against extracellular pathogens by binding to antigens, thereby neutralizing pathogens or making them better targets for phagocytes and complement proteins. Defend against intracellular pathogens and cancer by binding to and lysing the infected cells or cancer cells. Slide 51 of 106 Secreted antibodies Defend against extracellular pathogens opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 52 of 106 ell-mediated immune response Antigen (1st exposure) Engulfed by Antigenpresenting cell Helper T cell Memory Helper T cells Antigen (2nd exposure) Memory ytotoxic T cells Key Stimulates Gives rise to ytotoxic T cell Active ytotoxic T cells Helper T ells: A Response to Nearly All Antigens Helper T cells respond to nearly all antigens A surface protein called D4 binds the class II MH This binding keeps the helper T cell joined to the antigen-presenting cell while activation occurs Activated helper T cells secrete cytokines that stimulate other lymphocytes Defend against intracellular pathogens opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 53 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 54 of 106 9

10 The central role of helper T cells in humoral and cell-mediated immune responses Antigenpresenting cell Bacterium Peptide antigen Humoral immunity (secretion of antibodies by plasma cells) ytokines B cell lass II MH D4 TR (T cell receptor) Helper T cell ytotoxic T cell ell-mediated immunity (attack on infected cells) Animation: Helper T ells Right-click slide / select Play 2011 Pearson Education, Inc. opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 56 of 106 ell-mediated Immunity ytotoxic T cells destroy infected cells ytotoxic T cells are the effector cells in cell-mediated immune response ytotoxic T cells make D8, a surface protein that greatly enhances interaction between a target cell and a cytotoxic T cell Binding to a class I MH complex on an infected cell activates a cytotoxic T cell and makes it an active killer The activated cytotoxic T cell secretes proteins (perforins) that destroy the infected target cell by making membranes porous. opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 57 of 106 The killing action of cytotoxic T cells ytotoxic T cell D8 lass I MH Target cell Perforin Granzymes TR Peptide antigen opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 58 of 106 The killing action of cytotoxic T cells The killing action of cytotoxic T cells Released cytotoxic T cell ytotoxic T cell ytotoxic T cell Perforin Perforin Granzymes Granzymes D8 lass I MH TR Pore D8 lass I MH TR Pore Dying target cell Target cell Peptide antigen Target cell Peptide antigen opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 59 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 60 of

11 Fighting ancer 43_18ytotoxicTells_A.s wf Animation: ytotoxic T ells Right-click slide / select Play 2011 Pearson Education, Inc. opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 62 of 106 Humoral Immunity B cells: Humoral Immunity The humoral response is characterized by secretion of antibodies by B cells into extracellular fluid (humor) Activation of B cells is aided by cytokines and antigen binding to helper T cells lonal selection of B cells generates antibody-secreting plasma cells, the effector cells of humoral immunity B cell activation in the humoral immune response Antigen-presenting cell Bacterium Peptide antigen lass II MH TR D4 Helper T cell opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 63 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 64 of 106 B cell activation in the humoral immune response B cell activation in the humoral immune response Antigen-presenting cell Bacterium Antigen-presenting cell Bacterium Peptide antigen B cell Peptide antigen B cell lass II MH TR D4 ytokines lass II MH TR D4 lone of plasma cells Secreted antibody ytokines s Helper T cell Activated helper T cell Helper T cell Activated helper T cell lone of memory B cells opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 65 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 66 of

12 B cell activation in the humoral immune response Endoplasmic reticulum of plasma cell 2 µm Humoral Immunity Antibodies The five major classes of antibodies, or immunoglobulins, differ in distribution and function Polyclonal antibodies are the products of many different clones of B cells following exposure to a microbial antigen Monoclonal antibodies are prepared from a single clone of B cells grown in culture opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 67 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 68 of 106 The five antibody, or immunoglobulin (Ig), classes The five antibody, or immunoglobulin (Ig), classes lass of Immunoglobulin (Antibody) IgM (pentamer) J chain Distribution First Ig class produced after initial exposure to antigen; then its concentration in the blood declines Function Promotes neutralization and crosslinking of antigens; very effective in complement system activation lass of Immunoglobulin (Antibody) IgG (monomer) Distribution Most abundant Ig class in blood; also present in tissue fluids Function Promotes opsonization, neutralization, and cross-linking of antigens; less effective in activation of complement system than IgM Only Ig class that crosses placenta, thus conferring passive immunity on fetus opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 69 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 70 of 106 The five antibody, or immunoglobulin (Ig), classes The five antibody, or immunoglobulin (Ig), classes lass of Immunoglobulin (Antibody) IgA (dimer) Secretory component J chain Distribution Present in secretions such as tears, saliva, mucus, and breast milk Function Provides localized defense of mucous membranes by cross-linking and neutralization of antigens Presence in breast milk confers passive immunity on nursing infant lass of Immunoglobulin (Antibody) IgE (monomer) Distribution Present in blood at low concentrations Function Triggers release from mast cells and basophils of histamine and other chemicals that cause allergic reactions opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 71 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 72 of

13 The five antibody, or immunoglobulin (Ig), classes lass of Immunoglobulin (Antibody) IgD (monomer) Transmembrane region Distribution Present primarily on surface of B cells that have not been exposed to antigens Function Acts as antigen receptor in the antigen-stimulated proliferation and differentiation of B cells (clonal selection) The Role of Antibodies in Immunity The role of antibodies in immunity Neutralization occurs when a pathogen can no longer infect a host because it is bound to an antibody Opsonization occurs when antibodies bound to antigens increase phagocytosis Antibodies together with proteins of the complement system generate a membrane attack complex and cell lysis Animation: Antibodies opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 73 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 74 of 106 Antibody-mediated mechanisms of antigen disposal Viral neutralization Virus Animation: Antibodies Right-click slide / select Play 2011 Pearson Education, Inc. opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 76 of 106 Antibody-mediated mechanisms of antigen disposal Opsonization Bacterium Activation of complement system and pore formation omplement proteins Formation of membrane attack complex Macrophage Flow of water and ions Pore Foreign cell opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 77 of 106 Slide 78 of

14 Fig. 43-UN1 Elimination of self-reactive B cells Stem cell ell division and gene rearrangement lonal selection Formation of activated cell populations Memory cells Effector B cells Microbe Antigen Receptors bind to antigens Antibody Active and Passive Immunization Active and passive immunity Active immunity develops naturally in response to an infection It can also develop following immunization, also called vaccination In immunization, a nonpathogenic form of a microbe or part of a microbe elicits an immune response to an immunological memory Slide 79 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 80 of 106 Immunizations Active and Passive Immunity Passive immunity provides immediate, short-term protection It is conferred naturally when IgG crosses the placenta from mother to fetus or when IgA passes from mother to infant in breast milk It can be conferred artificially by injecting antibodies into a nonimmune person opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 81 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 82 of 106 Immune Rejection Immune rejection The immune system s ability to distinguish self from nonself limits tissue transplantation ells transferred from one person to another can be attacked by immune defenses This complicates blood transfusions or the transplant of tissues or organs opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 83 of 106 Immune Rejection Blood types Antigens on red blood cells determine whether a person has blood type A (A antigen), B (B antigen), AB (both A and B antigens), or O (neither antigen) Antibodies to nonself blood types exist in the body Transfusion with incompatible blood leads to destruction of the transfused cells Recipient-donor combinations can be fatal or safe opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 84 of

15 Recipient-donor combinations Table 43.1 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 85 of 106 Blood Types Rh factor, a RB antigen Rh positive RBs have the antigen Rh negative cells do not have the antigen and therefore carry antibodies for it. reates difficulties when an Rh negative mother carries successive Rh positive babies First baby: primary response memory B cells are generated to Rh baby Second baby: antibodies IgG are produced quickly which can cross placenta and destroy baby s RB s opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 86 of 106 Rh factor and pregnancy: The mother may be given a shot at 28 weeks that prevents her from making antibodies for the Rh factor Immune Rejection Tissue and organ transplants MH s are different among genetically nonidentical individuals Differences in MH s stimulate rejection of tissue grafts and organ transplants Lymphocytes in bone marrow transplants may cause the donor tissue to reject the recipient opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 87 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 88 of 106 Immune Rejection Preventing organ rejection hances of successful transplantation increase if donor and recipient MH tissue types are well matched Immunosuppressive drugs facilitate transplantation Lymphocytes in bone marrow transplants may cause the donor tissue to reject the recipient oncept 43.4: Disruption in immune system function can elicit or exacerbate disease Disruption in immune system function can elicit or exacerbate disease Exaggerated immune response (allergies) Self-directed immune response (autoimmune diseases) Diminished immune responses opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 89 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 90 of

16 Allergies Allergies Allergies are exaggerated (hypersensitive) responses to antigens called allergens In localized allergies such as hay fever, IgE antibodies produced after first exposure to an allergen attach to receptors on mast cells Mast cells, IgE, and the allergic response IgE Allergen Granule Mast cell Histamine opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 91 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 92 of 106 Allergies The next time the allergen enters the body, it binds to mast cell associated IgE s Mast cells release histamine and other mediators that cause vascular changes leading to typical allergy symptoms An acute allergic response can lead to anaphylactic shock, a life-threatening reaction that can occur within seconds of allergen exposure Autoimmune Diseases Autoimmune diseases In individuals with autoimmune diseases, the immune system loses tolerance for self and turns against certain s of the body Autoimmune diseases include systemic lupus erythematosus, rheumatoid arthritis, insulindependent diabetes mellitus, and multiple sclerosis opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 93 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 94 of 106 X-ray of a hand deformed by rheumatoid arthritis Immunodeficiency Diseases Immunodeficiency diseases Inborn immunodeficiency results from hereditary or developmental defects that prevent proper functioning of innate, humoral, and/or cell-mediated defenses Acquired immunodeficiency results from exposure to chemical and biological agents Acquired immunodeficiency syndrome (AIDS) is caused by a virus opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 95 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 96 of

17 Exertion, Stress, and the Immune System Diminished immune response Moderate exercise improves immune system function Psychological stress has been shown to disrupt hormonal, nervous, and immune systems Latency Latent viruses Some viruses may remain in a host in an inactive state called latency Herpes simplex viruses can be present in a human host without causing symptoms opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 97 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 98 of 106 Attack on the Immune System: HIV Attack on the immune system: HIV Human immunodeficiency virus (HIV) infects helper T cells The loss of helper T cells impairs both the humoral and cell-mediated immune responses and leads to AIDS HIV eludes the immune system because of antigenic variation and an ability to remain latent while integrated into host DNA 43_26HIVReproycle_A.s wf Animation: HIV Reproductive ycle Right-click slide / select Play opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 99 of Pearson Education, Inc. The progress of an untreated HIV infection Helper T cell concentration in blood (cells/mm 3 ) Latency Relative antibody concentration Relative HIV concentration Helper T cell concentration AIDS AIDS People with AIDS are highly susceptible to opportunistic infections and cancers that take advantage of an immune system in collapse The spread of HIV is a worldwide problem The best approach for slowing this spread is education about practices that transmit the virus Years after untreated infection opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 101 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 102 of

18 ancer and Immunity ancer and immunity The frequency of certain cancers increases when the immune response is impaired Two suggested explanations are Immune system normally suppresses cancerous cells Increased inflammation increases the risk of cancer You should now be able to: 1. Distinguish between innate and acquired immunity 2. Describe the inflammation response 3. Distinguish between the following pairs of terms: antigens and antibodies; antigen and epitope; B lymphocytes and T lymphocytes; antibodies and B cell receptors; primary and secondary immune responses; humoral and cell-mediated response; active and passive immunity opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 103 of 106 opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 104 of Explain how B lymphocytes and T lymphocytes recognize specific antigens 5. Explain why the antigen receptors of lymphocytes are tested for self-reactivity 7. Describe clonal selection and distinguish between effector cells and memory cells 8. Describe the cellular basis for immunological memory opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 105 of Explain how a single antigen can provoke a robust humoral response 10. Explain why a secondary immune response is must more efficient at fighting an infection than a primary immune response 11. Describe the role of MH in the rejection of tissue transplants 12. Describe an allergic reaction, including the roles of IgE, mast cells, and histamine 13. List strategies that can reduce the risk of HIV transmission opyright 2008 Pearson Education Inc., publishing as Pearson Benjamin ummings Slide 106 of

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