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Chapter 43:The Immune System (Body’s Defense Mechanisms) Barriers help an animal to defend itself from the many dangerous pathogens it may encounter The Immune System and its Responses • The immune system recognizes foreign bodies and responds with the production of immune cells and proteins • 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 43-2 Pathogens (microorganisms and viruses) INNATE IMMUNITY • Recognition of traits shared by broad ranges of pathogens, using a small set of receptors • Rapid response ACQUIRED IMMUNITY • Recognition of traits specific to particular pathogens, using a vast array of receptors • Slower response Barrier defenses: Skin Mucous membranes Secretions Internal defenses: Phagocytic cells Antimicrobial proteins Inflammatory response Natural killer cells Humoral response: Antibodies defend against infection in body fluids. Cell-mediated response: Cytotoxic lymphocytes defend against infection in body cells. INNATE IMMUNITY: Barrier Defenses A. Skin 1. physical barrier 2. skin and oil: pH of 3-5 3. saliva and tears a. wash away invaders b. lysozyme- breaks down cell walls of bacteria B. Mucous 1. traps particles 2. lines digestive, respiratory and urinary tracts Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings INNATE IMMUNITY: Cellular Innate Defenses C. Phagocytic Lymphocytes 1. Neutrophils a. attracted by chemicals (chemotaxis), leave blood stream by amoeboid movement b. self destruct as they destroy invaders 2. Monocytes a. migrate into tissues and enlarge to form macrophages: effective, long-living phagocytes b. some macrophages are specialized for specific organs: 1. lungs: alveolar macrophages 2. liver: Kupffer’s cells 3. lymph nodes 4. spleen Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings INNATE IMMUNITY: Cellular Innate Defenses 3. Eosinophils a. limited phagocytic activity b. contain enzymes in granules c. defense against parasitic invaders (worms) 4. Natural Killer Cells 1. destroy body’s own infected cells 2. also destroy cancer cells 3. attack cell membrane -> cell lyses Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings INNATE IMMUNITY: Antimicrobial Proteins E. Antimicrobial proteins 1. Complement system: a. group of ~30 proteins b. cascade of reactions -> lysis of invading cell 2. Interferons: a. chemicals secreted by virus-infected cells b. interfere with viral replication c. most effective with short-term infections (ex- flu, cold) Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings INNATE IMMUNITY: Inflammatory Responses F. Inflammatory Response (localized) 1. small blood vessels dilate -> redness & heat 2. fluids move from blood to tissues -> edema 3. initiated by chemical signals a. basophils and mast cells release histamines b. WBCs discharge prostaglandins 4. Enhances migration of phagocytes to injury site 5. pus= dead cells (neutrophils) and fluid Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 43-8-3 Inflammatory Response Joe gets a Splinter : ( Pathogen Splinter Chemical Macrophage signals Mast cell Capillary Red blood cells Phagocytic cell Fluid Phagocytosis INNATE IMMUNITY: Inflammatory Responses G. Systemic Responses (ex. appendicitis) 1. Increase in number of WBCs 2. fever a. WBCs release pyrogens which set body’s thermostat higher b. inhibits growth of microorganisms c. speeds up body’s reactions -> quick repair • Septic shock is a life-threatening condition caused by an overwhelming inflammatory response Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings 43.2 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 http://www.youtube.com/watch?v=G7rQuFZxVQQ&feature=related&safety_mode=true&persist_safety_mode=1 http://www.youtube.com/watch?v=k_GPGrl5HDM&feature=related http://www.youtube.com/watch?v=_bNN95sA6-8&feature=related&safety_mode=true&persist_safety_mode=1 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 43-2 Pathogens (microorganisms and viruses) INNATE IMMUNITY • Recognition of traits shared by broad ranges of pathogens, using a small set of receptors • Rapid response ACQUIRED IMMUNITY • Recognition of traits specific to particular pathogens, using a vast array of receptors Barrier defenses: Skin Mucous membranes Secretions Internal defenses: Phagocytic cells Antimicrobial proteins Inflammatory response Natural killer cells Humoral response: Antibodies defend against infection in body fluids. Cell-mediated response: Cytotoxic lymphocytes defend against infection in body cells. • Slower response Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings II. ACQUIRED IMMUNITY: An Overview A. Immune System 1. Consists of: a. lymph- fluid, WBCs, and wastes or antigens b. lymph nodes- small masses of tissue that filter lymph and destroy antigens c. spleen- larger lymphatic organ that filters blood of antigens and dead blood cells d. tonsils- lymphatic organ that defends against antigens in nose and mouth e. thymus- most prominent in children- helps develop immune response (T cells) Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 43-7 Interstitial fluid Adenoid Tonsil Blood capillary Lymph nodes Spleen Tissue cells Lymphatic vessel Peyer’s patches (small intestine) Appendix Lymphatic vessels http://www.enile.co.uk/portfolio/cancer/lymph01.html Lymph node Masses of defensive cells 2. Qualities of the immune system a. Specificity- ability to recognize and eliminate particular microbes 1. antigen= foreign substance (ex- virus, bacteria, parasite, pollen, foreign organs) 2. antibody= specific protein to recognize antigen Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings b. Diversity- ability to respond to millions of kinds of invaders due to enormous variety of lymphocytes c. Self/Non-self recognition - ability to distinguish own molecules from foreign molecules d. Memory- ability to remember antigens and attack them = acquired immunity 1. active immunity- body makes antibodies(ex- chicken pox and vaccinations) 2. passive immunity- mother passes antibodies to fetus across placenta or through breast milk Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings B. Lymphocytes 1. All blood cells originate from stem cells in the bone marrow 2. Lymph cells then differentiate a. mature in thymus- T cell b. mature in bone marrow- B cell Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings 3. B (bursa of Fabricius) cells a. have antigen receptors on cell membrane b. humoral immunityproduction of antibodies secreted by B cells and circulated as soluble proteins in blood and lymph c. B cells activated by antigens divide and give rise to effector cells- secrete antibodies Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings 4. T (thymus) cells a. have receptors on cell membrane b. T cells activated by antigens divide and give rise to: 1. cytotoxic (killer) T cells- destroy infected cells and cancer cells 2. helper T cellsstimulate both humoral and cell-mediated immunity c. cell mediated immunity: depends on the direct action of cells (not antibodies) Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 43-9 Antigenbinding site Antigenbinding site Antigenbinding site Disulfide bridge C C Light chain Variable regions V V Constant regions C C Transmembrane region Plasma membrane Heavy chains chain chain Disulfide bridge B cell (a) B cell receptor Cytoplasm of B cell Cytoplasm of T cell (b) T cell receptor T cell C. Antigen-Antibody Specificity 1. epitope- region on the surface of an antigen that antibody recognizes 2. Antibodies are a class of proteins called immunoglobulins. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings 3. Typical antibody a. structure C= constant region; same amino acid sequence for all antibodies V= variable region= antigen-binding site b. association between antigen binding site and epitope = lock & key (like enzyme-subtrate) c. 5 types of constant regions which allow for different defense functions Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 43-10 Antigenbinding sites Antigen-binding sites Antibody A Antigen Antibody C C C Antibody B Epitopes (antigenic determinants) Fig. 43-20a Class of Immunoglobulin (Antibody) IgM (pentamer) Distribution First Ig class produced after initial exposure to antigen; then its concentration in the blood declines J chain Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Function Promotes neutralization and crosslinking of antigens; very effective in complement system activation Fig. 43-20b Class 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 43-20c Class of Immunoglobulin (Antibody) IgA (dimer) J chain Distribution Present in secretions such as tears, saliva, mucus, and breast milk Secretory component Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Function Provides localized defense of mucous membranes by cross-linking and neutralization of antigens Presence in breast milk confers passive immunity on nursing infant Fig. 43-20d Class of Immunoglobulin (Antibody) IgE (monomer) Distribution Present in blood at low concentrations Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Function Triggers release from mast cells and basophils of histamine and other chemicals that cause allergic reactions Fig. 43-20e Class of Immunoglobulin (Antibody) IgD (monomer) Distribution Present primarily on surface of B cells that have not been exposed to antigens Transmembrane region Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Function Acts as antigen receptor in the antigen-stimulated proliferation and differentiation of B cells (clonal selection) D. Clonal Selection 1. Each lymphocyte’s antigenic target is predetermined during embryonic development 2. Clonal selection- when antigen enters body, lymphocyte is activated and divides to make many effector cells = “clones” http://student.ccbcmd.edu/courses/bio141/lecguide/ unit5/humoral/clonal/clonalan.html Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 43-14 Antigen molecules B cells that differ in antigen specificity Antigen receptor Antibody molecules Clone of memory cells Clone of plasma cells Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings E. Cellular Memory 1. Primary Immune Response = clonal selection a. effector cells and memory cells made b. 5-10 days lag time 2. Secondary Immune Response a. 2nd exposure to the antigen -> response faster (3-5 days) b. memory cells- live long time & divide quickly Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 43-15 Antibody concentration (arbitrary units) Primary immune response to antigen A produces antibodies to A. Secondary immune response to antigen A produces antibodies to A; primary immune response to antigen B produces antibodies to B. 104 103 Antibodies to A 102 Antibodies to B 101 100 0 7 Exposure to antigen A 14 21 28 35 42 Exposure to antigens A and B Time (days) Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings 49 56 Fig. 43-16 Humoral (antibody-mediated) immune response Cell-mediated immune response Key Antigen (1st exposure) + Engulfed by Gives rise to Antigenpresenting cell + Stimulates + + B cell Helper T cell + Cytotoxic T cell + Memory Helper T cells + + + Antigen (2nd exposure) Plasma cells Memory B cells + Memory Cytotoxic T cells Active Cytotoxic T cells Secreted antibodies Defend against extracellular pathogens by binding to antigens, thereby neutralizing pathogens or making them better targets for phagocytes and complement proteins. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Defend against intracellular pathogens and cancer by binding to and lysing the infected cells or cancer cells. 43.3 Self-Tolerance 1. There are no antigen receptors for animal’s own molecules. 2. MHC (major histocompatibility complex): glycoproteins on membrane = “self marker” – Class I MHC molecules are found on almost all nucleated cells of the body In infected cells, MHC molecules bind and transport antigen fragments to the cell surface, a process called antigen presentation Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 43-2 Pathogens (microorganisms and viruses) INNATE IMMUNITY • Recognition of traits shared by broad ranges of pathogens, using a small set of receptors •Rapid response ACQUIRED IMMUNITY • Recognition of traits specific to particular pathogens, using a vast array of receptors Barrier defenses: Skin Mucous membranes Secretions Internal defenses: Phagocytic cells Antimicrobial proteins Inflammatory response Natural killer cells Humoral response: Antibodies defend against infection in body fluids. Cell-mediated response: Cytotoxic lymphocytes defend against infection in body cells. • Slower response Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings The acquired immune system has three important properties: 1. Receptor diversity 2. A lack of reactivity against host cells 3.Immunological memory Fig. 43-16a Humoral (antibody-mediated) immune response Key + Antigen (1st exposure) Stimulates Gives rise to Engulfed by Antigenpresenting cell + + B cell Helper T cell + Memory Helper T cells + Plasma cells + Antigen (2nd exposure) Memory B cells Secreted antibodies Defend against extracellular pathogens + III. Humoral Response A. Activating B cells (to make antibodies) 1. Antigen binds to receptor on Bcell or 2. Macrophage engulfs pathogens and pieces displayed on cell membrane = Antigen Presenting Cell 3. Helper T cells recognize self/non-self combination of MHC & APC -> activates T cells -> stimulate B cells to mount a humoral response Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 43-19 Antigen-presenting cell Bacterium Peptide antigen B cell Class II MHC molecule TCR Clone of plasma cells + CD4 Cytokines Secreted antibody molecules Endoplasmic reticulum of plasma cell Helper T cell Activated helper T cell Clone of memory B cells 2 µm B. How Antibodies Work 1. Neutralization a. attaching to antigen at site in which it binds to host b. coating a bacterial toxin with antibody 2. Agglutination (opsonization)- bacteria clump together; easier to engulf by phagocytosis 3. Work with Complements a. complement bridges the gap between two adjacent antibodies -> forms membrane attack complex ->lesion -> cell lyses Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 43-21 Viral neutralization Opsonization Activation of complement system and pore formation Bacterium Complement proteins Virus Formation of membrane attack complex Flow of water and ions Macrophage Pore Foreign cell Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings 4. Monoclonal antibodies a. all identical b. technology to make large quantities of pure antibody c. can be used diagnostically (combat microbes) or for treatment (possibly cancer) Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 43-16b Cell-mediated immune response Key + Antigen (1st exposure) Engulfed by Antigenpresenting cell Stimulates Gives rise to + + Helper T cell Cytotoxic T cell + Memory Helper T cells + + Antigen (2nd exposure) + Active Cytotoxic T cells Memory Cytotoxic T cells Defend against intracellular pathogens IV. Cell-mediated response A. Respond to antigen epitope- MHC marker complex B. When activated, clones effector cells to form: 1. Helper T cells -> activate B cells 2. Cytotoxic T cells a. Bind to specific antigen-MHC marked cells b. release perforin -> forms lesions -> lysis 1. destroys host cell 2. exposes pathogen to antibodies 3. defends against cancer Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 43-17 Antigenpresenting cell Peptide antigen Bacterium Class II MHC molecule CD4 TCR (T cell receptor) Helper T cell Humoral immunity (secretion of antibodies by plasma cells) Cytokines + B cell + + + Cytotoxic T cell Cell-mediated immunity (attack on infected cells) Fig. 43-18-3 Released cytotoxic T cell Cytotoxic T cell Perforin Granzymes CD8 TCR Class I MHC molecule Target cell Dying target cell Pore Peptide antigen V. Self Versus Nonself A. Blood Groups 1. Blood Type Antigen Antibodies A A B B B A O none A&B AB AB none 2. Rh factor=antigen (important during pregnancy) Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings • Antibodies to non-self 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings B. Organ Transplants 1. MHC responsible for rejection 2. Cytotoxic T cells mount a cell-mediated response 3. Immune system suppressed Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings 43.4 Disorders 1. Autoimmune diseases- don’t recognize own MHC a. rheumatoid arthritis (cartilage attacked) b. Insulin-dependent diabetes (pancreas attacked) c. Grave’s Disease (thyroid attacked -> excessive hormone) Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings D. Allergies 1. hypersensitivities to environmental antigens = allergens 2. antibodies attach to mast cells -> histamines released -> dilation of small blood vessels -> runny nose, sneezing, breathing difficulty (smooth muscle contraction) 3. anaphylactic shock- histamines trigger rapid dilation of capillaries -> low BP -> shock or death Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Antigenic Variation • Through antigenic variation, some pathogens are able to change epitope expression and prevent recognition • The human influenza virus mutates rapidly, and new flu vaccines must be made each year • Human viruses occasionally exchange genes with the viruses of domesticated animals • This poses a danger as human immune systems are unable to recognize the new viral strain Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings E. Immunodeficiency 1. can be inborn- bone marrow transplant may help 2. Hodgkin’s disease- a type of cancer that depresses the immune response 3. AIDS- Acquired Immunodeficiency Syndrome a. HIV binds to CD4 markers on helper T cells, some macrophages and a few B cells b. Virus may remain dormant for many years c. Virus replicates inside cell and GP 120 protein starts to appear on surface of helper T cells d. Cytotoxic T cells and Natural killer cells attack and destroy helper T cells marked with GP120 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings http://highered.mcgrawhill.com/sites/0072495855/student_view0/chapter24/animation__how_the_hiv_infection_cycle_works.html e. Why can’t body fight it? 1. dormancy- no antibodies formed 2. mutates QUICKLY! 3. number of viruses- number of T cells f. death results from opportunistic diseases g. transmitted through body fluids h. life expectancy increased through drug therapies (AZT/protease inhibitors) Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 43-26 AIDS Helper T cell concentration in blood (cells/mm3) Latency Relative antibody concentration 800 Relative HIV concentration 600 Helper T cell concentration 400 200 0 0 1 2 3 4 5 6 7 8 Years after untreated infection 9 10 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings • 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings • http://highered.mcgrawhill.com/sites/0072437316/student_view0/chapter48/animations.html# Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings