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Chapter 21A Immune System: Innate and Adaptive Defenses Slides by Barbara Heard and W. Rose. figures from Marieb & Hoehn 9th ed. Portions copyright Pearson Education Nobel Prizes for Immune System Discoveries 2011 Beutler, Hoffmann, Steinman, "for their discoveries concerning the activation of innate immunity”; “for his discovery of the dendritic cell and its role in adaptive immunity” [H: Toll receptors in fruit flies essential for innate immunity. B: Found Tolllike receptors in mammals & clarified their important role in innate immunity. S: Discovered dendritic cells & showed they have special ability to present antigens to & activate naïve T cells. Langerhans cells in skin Dead fruit fly with fungus growing on it because it has mutant are a subtype of DCs.] Toll receptors. …&Hoffman, Cell, 1996. Nobel Prizes for Immune System Discoveries 1996 Doherty, Zinkernagel “for their discoveries concerning the specificity of the cell mediated immune defence” [Discovered that killer T cells recognize virus-infected cells by simultaneous recognition of self & non-self markers. Explains benefits of HLA, which is a barrier to organ transplant.] 1987 Susumu Tonegawa "for his discovery of the genetic principle for generation of antibody diversity“ [how to make millions of antibodiy proteins from a small number of genes by genetic shuffling] Nobel Prizes for Immune System Discoveries 1984 Jerne, Köhler, Milstein "for theories concerning the specificity in development and control of the immune system and the discovery of the principle for production of monoclonal antibodies" [Jerne: we are born with a full repertoire of antibodies and select the needed ones when we encounter a new pathogen. K. & M.: fused lymphocytes with tumor cells to create immortal cells (hybridomas) that make one antibody specifically] Nobel Prizes for Immune System Discoveries 1980 Benacerraf, Dausset, Snell "for their discoveries concerning genetically determined structures on the cell surface that regulate immunological reactions“ [discovery & understanding of MHC (HLA in humans)] 1972 Edelman, Porter "for their discoveries concerning the chemical structure of antibodies“ [Y shape, heavy & light chains, constant & variable regions] Nobel Prizes for Immune System Discoveries 1960 Burnet, Medawar "for discovery of acquired immunological tolerance“ [Burnet: “immunological tolerance”; both showed how early immune system cells become self-tolerant] 1930 Landsteiner "for his discovery of human blood groups" [blood groups and blood typing] 1919 Bordet "for his discoveries relating to immunity" [antigens and antibodies] Nobel Prizes for Immune System Discoveries 1913 Richet "in recognition of his work on anaphylaxis“ [Discovered & coined term for anaphylaxis & elucidated how it occurs.] 1908 Mechnikov, Ehrlich "in recognition of their work on immunity" [Mechinov discovered & coined the term phagocytosis & phagocytes; Erlich discovered antibodies] Nobel Prizes for Immune System Discoveries 1901 von Behring "for his work on serum therapy, especially its application against diphtheria, by which he has opened a new road in the domain of medical science and thereby placed in the hands of the physician a victorious weapon against illness and deaths“ [von Behring discovered that when animals were injected with tiny doses of weakened forms of tetanus or diphtheria bacteria, their blood extracts contained chemicals released in response, which rendered the pathogens' toxins harmless.] Immune System: Links to articles Treating allergies with pills instead of shots NYT 20131206 The case against cleanliness: a skeptical review NYT 20120910 The boy with a thorn in his joints NYT 20130301 An interesting and moving article by a mother about her son, his juvenile idiopathic arthritis, and alternative medicine. Interesting comments too. Immunity • Resistance to disease • Immune system – Two intrinsic systems • Innate (nonspecific) defense system • Adaptive (specific) defense system © 2013 Pearson Education, Inc. Immune System • Functional system rather than organ system • Innate and adaptive defenses intertwined • Release and recognize many of same defensive molecules • Innate defenses do have specific pathways for certain substances • Innate responses release proteins that alert cells of adaptive system to foreign molecules © 2013 Pearson Education, Inc. Immunity • Innate defense system has two lines of defense – First - external body membranes (skin and mucosae) – Second - antimicrobial proteins, phagocytes, and other cells • Inhibit spread of invaders • Inflammation most important mechanism © 2013 Pearson Education, Inc. Immunity • Adaptive defense system – Third line of defense attacks particular foreign substances • Takes longer to react than innate system © 2013 Pearson Education, Inc. Figure 21.1 Overview of innate and adaptive defenses. Surface barriers • Skin • Mucous membranes Innate defenses Internal defenses • Phagocytes • Natural killer cells • Inflammation • Antimicrobial proteins • Fever Humoral immunity • B cells Adaptive defenses Cellular immunity • T cells © 2013 Pearson Education, Inc. Innate Defenses • Surface barriers ward off invading pathogens – Skin, mucous membranes, and their secretions • Physical barrier to most microorganisms • Keratin resistant to weak acids and bases, bacterial enzymes, and toxins • Mucosae provide similar mechanical barriers © 2013 Pearson Education, Inc. Surface Barriers • Protective chemicals inhibit or destroy microorganisms – Acidity of skin and secretions – acid mantle – inhibits growth – Enzymes - lysozyme of saliva, respiratory mucus, and lacrimal fluid – kill many microorganisms – Defensins – antimicrobial peptides – inhibit growth – Other chemicals - lipids in sebum, dermcidin in sweat – toxic © 2013 Pearson Education, Inc. Surface Barriers • Respiratory system modifications – Mucus-coated hairs in nose – Cilia of upper respiratory tract sweep dustand bacteria-laden mucus toward mouth • Surface barriers breached by nicks or cuts - second line of defense must protect deeper tissues © 2013 Pearson Education, Inc. Internal Defenses: Cells and Chemicals • Necessary if microorganisms invade deeper tissues – Phagocytic cells – Natural killer (NK) cells – Antimicrobial proteins (interferons and complement proteins) – Fever – Inflammatory response (macrophages, mast cells, WBCs, and inflammatory chemicals) © 2013 Pearson Education, Inc. Phagocytic cells • Neutrophils most abundant but die fighting – Become phagocytic on exposure to infectious material • Macrophages develop from monocytes – chief phagocytic cells © 2013 Pearson Education, Inc. Mechanism of Phagocytosis • Phagocyte must adhere to particle – Some microorganisms evade adherence with capsule • Opsonization marks pathogens—coating by complement proteins or antibodies • Cytoplasmic extensions bind to and engulf particle in vesicle © 2013 Pearson Education, Inc. Figure 21.2a Phagocytosis. Innate defenses © 2013 Pearson Education, Inc. Internal defenses A macrophage (purple) uses its cytoplasmic extensions to pull rod-shaped bacteria (green) toward it. Scanning electron micrograph (4800x). Figure 21.2b Phagocytosis. 1 Phagocyte adheres to pathogens or debris. Phagosome (phagocytic vesicle) Lysosome Acid hydrolase enzymes 2 Phagocyte forms pseudopods that eventually engulf the particles, forming a phagosome. 3 Lysosome fuses with the phagocytic vesicle, forming a phagolysosome. 4 Lysosomal enzymes digest the particles, leaving a residual body. 5 Exocytosis of the vesicle removes indigestible and residual material. Events of phagocytosis. © 2013 Pearson Education, Inc. Slide 1 Mechanism of Phagocytosis • Pathogens killed by acidifying and digesting with lysosomal enzymes • Helper T cells cause release of enzymes of respiratory burst, which kill pathogens resistant to lysosomal enzymes by – Releasing cell-killing free radicals – Producing oxidizing chemicals (e.g., H2O2) – Increasing pH and osmolarity of phagolysosome • Defensins (in neutrophils) pierce membrane © 2013 Pearson Education, Inc. Natural Killer (NK) Cells • Nonphagocytic large granular lymphocytes • Attack cells that lack "self" cell-surface receptors – Induce apoptosis in cancer cells and virusinfected cells • Secrete potent chemicals that enhance inflammatory response © 2013 Pearson Education, Inc. Inflammatory Response • • • • • Triggered whenever body tissues injured Prevents spread of damaging agents Disposes of cell debris and pathogens Alerts adaptive immune system Sets the stage for repair © 2013 Pearson Education, Inc. Inflammatory Response • Cardinal signs of acute inflammation: 1. Redness 2. Heat 3. Swelling 4. Pain (Sometimes 5. Impairment of function) © 2013 Pearson Education, Inc. Inflammatory Response • Begins with chemicals released into ECF by injured tissues, immune cells, blood proteins • Macrophages and epithelial cells of boundary tissues bear Toll-like receptors (TLRs) • 11 types of TLRs recognize specific classes of infecting microbes • Activated TLRs trigger release of cytokines that promote inflammation © 2013 Pearson Education, Inc. Inflammatory Response • Inflammatory mediators – Kinins, prostaglandins (PGs), and complement • Dilate local arterioles (hyperemia) – Causes redness and heat of inflamed region • Make capillaries leaky • Many attract leukocytes to area • Some have inflammatory roles © 2013 Pearson Education, Inc. Inflammatory Response: Edema • Capillary permeability exudate to tissues – Fluid containing clotting factors and antibodies – Causes local swelling (edema) – Swelling pushes on nerve endings pain • Pain also from bacterial toxins, prostaglandins, and kinins – Moves foreign material into lymphatic vessels – Delivers clotting proteins and complement © 2013 Pearson Education, Inc. Inflammatory Response • Clotting factors form fibrin mesh – Scaffold for repair – Isolates injured area so invaders cannot spread © 2013 Pearson Education, Inc. Figure 21.3 Inflammation: flowchart of events. Innate defenses Internal defenses Initial stimulus Physiological response Tissue injury Release of inflammatory chemicals (histamine, complement, kinins, prostaglandins, etc.) Signs of inflammation Result Release of leukocytosisinducing factor Leukocytosis (increased numbers of white blood cells in bloodstream) Arterioles dilate Increased capillary permeability Local hyperemia (increased blood flow to area) Capillaries leak fluid (exudate formation) Leaked protein-rich fluid in tissue spaces Heat Redness Locally increased temperature increases metabolic rate of cells Pain Attract neutrophils, monocytes, and lymphocytes to area (chemotaxis) Margination (leukocytes cling to capillary walls) Leaked clotting proteins form interstitial clots that wall off area to prevent injury to surrounding tissue Swelling Possible temporary impairment of function Temporary fibrin patch forms scaffolding for repair Healing © 2013 Pearson Education, Inc. Leukocytes migrate to injured area Diapedesis (leukocytes pass through capillary walls) Phagocytosis of pathogens and dead tissue cells (by neutrophils, short-term; by macrophages, long-term) Pus may form Area cleared of debris Phagocyte Mobilization • Neutrophils lead; macrophages follow – As attack continues, monocytes arrive • 12 hours after leaving bloodstream macrophages • These "late-arrivers" replace dying neutrophils and remain for clean up prior to repair • If inflammation is due to pathogens, complement will be activated; cells of adaptive immunity will arrive © 2013 Pearson Education, Inc. Phagocyte Mobilization • Steps for phagocyte mobilization 1. Leukocytosis: release of neutrophils from bone marrow in response to leukocytosisinducing factors from injured cells 2. Margination: neutrophils cling to walls of capillaries in inflamed area in response to CAMs 3. Diapedesis of neutrophils 4. Chemotaxis: inflammatory chemicals (chemotactic agent) promote positive chemotaxis of neutrophils © 2013 Pearson Education, Inc. Figure 21.4 Phagocyte mobilization. Innate defenses Internal defenses Inflammatory chemicals diffusing from the inflamed site act as chemotactic agents. 1 Leukocytosis. Neutrophils enter blood from bone marrow. © 2013 Pearson Education, Inc. Slide 1 2 Margination. Neutrophils cling to capillary wall. 4 Chemotaxis. Neutrophils follow chemical trail. Capillary wall Basement membrane Endothelium 3 Diapedesis. Neutrophils flatten and squeeze out of capillaries. Antimicrobial Proteins • Include interferons and complement proteins • Some attack microorganisms directly • Some hinder microorganisms' ability to reproduce © 2013 Pearson Education, Inc. Interferons • Family of immune modulating proteins – Have slightly different physiological effects • Viral-infected cells secrete IFNs (e.g., IFN alpha and beta) to "warn" neighboring cells – IFNs enter neighboring cells produce proteins that block viral reproduction and degrade viral RNA – IFN alpha and beta also activate NK cells © 2013 Pearson Education, Inc. Interferons • IFN gamma (immune interferon) – Secreted by lymphocytes – Widespread immune mobilizing effects – Activates macrophages • Since IFNs activate NK cells and macrophages, indirectly fight cancer • Artificial IFNs used to treat hepatitis C, genital warts, multiple sclerosis, hairy cell leukemia © 2013 Pearson Education, Inc. Figure 21.5 The interferon mechanism against viruses. Innate defenses Slide 1 Internal defenses Virus Viral nucleic acid 1 Virus New viruses enters cell. 2 Interferon genes switch on. 5 Antiviral proteins block viral reproduction. Antiviral mRNA DNA Nucleus mRNA for interferon 3 Cell produces interferon molecules. Interferon receptor Host cell 1 Infected by virus; makes interferon; is killed by virus © 2013 Pearson Education, Inc. Interferon Host cell 2 Binds interferon from cell 1; interferon induces synthesis of protective proteins 4 Interferon binding stimulates cell to turn on genes for antiviral proteins. Complement System (Complement) • ~20 blood proteins that circulate in inactive form • Include C1–C9, factors B, D, and P, and regulatory proteins • Major mechanism for destroying foreign substances • Our cells contain complement activation inhibitors © 2013 Pearson Education, Inc. Complement • Unleashes inflammatory chemicals that amplify all aspects of inflammatory response • Kills bacteria and certain other cell types by cell lysis • Enhances both innate and adaptive defenses © 2013 Pearson Education, Inc. Complement Activation • Three pathways to activation – Classical pathway • Antibodies bind to invading organisms and to complement components • Called complement fixation • First step in activation; more details later – Lectin pathway – Alternative pathway © 2013 Pearson Education, Inc. Complement Lectin pathway Lectins: proteins produced by liver Some bind to mannose (sugar) residues found on surface of many pathogens. When lectin binds, it can activate other proteins in the complement pathway. © 2013 Pearson Education, Inc. Complement Alternative pathway Complement system is in a continuous low level of activation Complement regulatory proteins on host cells (i.e. our own cells) keep complement system in check Many pathogens lack complement regulatory proteins, so their presence allows complement to become activated © 2013 Pearson Education, Inc. Complement Activation • Each pathway involves activation of proteins in an orderly sequence • Each step catalyzes the next • Each pathway converges on C3, which cleaves into C3a and C3b • Common terminal pathway initiated that – Enhances inflammation, promotes phagocytosis, causes cell lysis © 2013 Pearson Education, Inc. Complement Activation • Cell lysis begins when – C3b binds to target cell insertion of complement proteins called membrane attack complex (MAC) into cell's membrane – MAC forms and stabilizes hole in membrane influx of water lysis of cell • C3b also causes opsonization • C3a and other cleavage products amplify inflammation – Stimulate mast cells and basophils to release histamine – Attract neutrophils and other inflammatory cells © 2013 Pearson Education, Inc. Figure 21.6 Complement activation. Classical pathway Activated by antibodies coating target cell Lectin pathway Activated by lectins binding to specific sugars on microorganism’s surface Alternative pathway Activated spontaneously. Lack of inhibitors on microorganism’s surface allows process to proceed Together with other complement proteins and factors C3 C3a C3b MACs form from activated complement components (C5b and C6–C9) that insert into the target cell membrane, creating pores that can lyse the target cell. C3b C5b MAC Opsonization: Coats pathogen surfaces, which enhances phagocytosis C6 C7 C8 C9 C5a Enhances inflammation: Stimulates histamine release, increases blood vessel permeability, attracts phagocytes by chemotaxis, etc. Pore Complement proteins (C5b–C9) Membrane of target cell © 2013 Pearson Education, Inc. Fever • Abnormally high body temperature • Systemic response to invading microorganisms • Leukocytes and macrophages exposed to foreign substances secrete pyrogens • Pyrogens act on body's thermostat in hypothalamus, raising body temperature © 2013 Pearson Education, Inc. Fever • Benefits of moderate fever – Causes liver and spleen to sequester iron and zinc (needed by microorganisms) – Increases metabolic rate faster repair(?) © 2013 Pearson Education, Inc. Adaptive Defenses • Adaptive immune (specific defense) system – Protects against infectious agents and abnormal body cells – Amplifies inflammatory response – Activates complement – Must be primed by initial exposure to specific foreign substance • Priming takes time © 2013 Pearson Education, Inc. Adaptive Defenses • Specific – recognizes and targets specific antigens • Systemic – not restricted to initial site • Have memory – stronger attacks to "known" antigens • Two separate, overlapping arms – Humoral (antibody-mediated) immunity – Cellular (cell-mediated) immunity © 2013 Pearson Education, Inc. Humoral Immunity • Antibodies, produced by lymphocytes, circulating freely in body fluids • Bind temporarily to target cell – Temporarily inactivate – Mark for destruction by phagocytes or complement • Humoral immunity has extracellular targets © 2013 Pearson Education, Inc. Cellular Immunity • Lymphocytes act against target cell – Directly – by killing infected cells – Indirectly – by releasing chemicals that enhance inflammatory response; or activating other lymphocytes or macrophages • Cellular immunity has cellular targets © 2013 Pearson Education, Inc. Antigens • Antibody Generators • Substances that can mobilize adaptive defenses and provoke an immune response • Targets of all adaptive immune responses • Most are large, complex molecules not normally found in body (nonself) © 2013 Pearson Education, Inc. Complete Antigens • Important functional properties – Immunogenicity: ability to stimulate proliferation of specific lymphocytes – Reactivity: ability to react with activated lymphocytes and antibodies released by immunogenic reactions • Examples: foreign protein, polysaccharides, lipids, and nucleic acids © 2013 Pearson Education, Inc. Haptens (Incomplete Antigens) • Small molecules (haptens) not immunogenic by themselves – E.g., peptides, nucleotides, some hormones • May be immunogenic if attached to body proteins and combination is marked foreign • Cause immune system to mount harmful attack • Examples: poison ivy, animal dander, detergents, and cosmetics © 2013 Pearson Education, Inc. Antigenic Determinants • Only certain parts (antigenic determinants) of entire antigen are immunogenic • Antibodies and lymphocyte receptors bind to them as enzyme binds substrate © 2013 Pearson Education, Inc. Antigenic Determinants • Most naturally occurring antigens have numerous antigenic determinants that – Bind to different antibodies – Mobilize several different lymphocyte populations • Large, chemically simple molecules (e.g., plastics) have little or no immunogenicity © 2013 Pearson Education, Inc. Figure 21.7 Most antigens have several different antigenic determinants. Antigenbinding sites Antibody A Antigen Antibody B Antibody C © 2013 Pearson Education, Inc. Antigenic determinants Self-antigens: MHC Proteins • Protein molecules (self-antigens) on surface of cells not antigenic to self but antigenic to others in transfusions or grafts • Example: MHC glycoproteins – Coded by genes of major histocompatibility complex (MHC) and unique to individual © 2013 Pearson Education, Inc. Cells of the Adaptive Immune System – Two types of lymphocytes • B lymphocytes (B cells)—humoral immunity • T lymphocytes (T cells)—cellular immunity – Antigen-presenting cells (APCs) • Do not respond to specific antigens • Play essential auxiliary roles in immunity © 2013 Pearson Education, Inc. Figure 21.8 Lymphocyte development, maturation, and activation. Adaptive defenses Primary lymphoid organs (red bone marrow and thymus) Humoral immunity Cellular immunity Secondary lymphoid organs (lymph nodes, spleen, etc.) Red bone marrow 1 Origin • Both B and T lymphocyte precursors originate in red bone marrow. Lymphocyte precursors 2 Maturation • Lymphocyte precursors destined to become T cells migrate (in blood) to the thymus and mature there. • B cells mature in the bone marrow. • During maturation lymphocytes develop immunocompetence and self-tolerance. Thymus Red bone marrow Antigen Lymph node 3 Seeding secondary lymphoid organs and circulation • Immunocompetent but still naive lymphocytes leave the thymus and bone marrow. • They “seed” the secondary lymphoid organs and circulate through blood and lymph. 4 Antigen encounter and activation • When a lymphocyte’s antigen receptors bind its antigen, that lymphocyte can be activated. 5 Proliferation and differentiation • Activated lymphocytes proliferate (multiply) and then differentiate into effector cells and memory cells. • Memory cells and effector T cells circulate continuously in the blood and lymph and throughout the secondary lymphoid organs. © 2013 Pearson Education, Inc. Slide 1 Maturation • "Educated" to become mature; B cells in bone marrow, T cells in thymus – Immunocompetence – lymphocyte can recognize one specific antigen by binding to it • B or T cells display only one unique type of antigen receptor on surface when achieve maturity – bind only one antigen – Self-tolerance • Lymphocytes unresponsive to own antigens © 2013 Pearson Education, Inc. T cells • T cells mature in thymus under negative and positive selection pressures ("tests") – Positive selection • Selects T cells capable of recognizing self-MHC proteins (MHC restriction); failures destroyed by apoptosis – Negative selection • Prompts apoptosis of T cells that bind to selfantigens displayed by self-MHC • Ensures self-tolerance © 2013 Pearson Education, Inc. Figure 21.9 T cell education in the thymus. Adaptive defenses Cellular immunity 1. Positive Selection T cells must recognize self major histocompatibility proteins (self-MHC) AntigenDeveloping presenting T cell thymic cell Failure to recognize selfMHC results in apoptosis (death by cell suicide). T cell receptor Self-MHC Self-antigen Recognizing self-MHC results in survival. Survivors proceed to negative selection. 2. Negative Selection T cells must not recognize self-antigens Recognizing self-antigen results in apoptosis. This eliminates self-reactive T cells that could cause autoimmune diseases. Failure to recognize (bind tightly to) self-antigen results in survival and continued maturation. © 2013 Pearson Education, Inc. B cells • B cells mature in red bone marrow • Positively selected if successfully make antigen receptors • Those that are self-reactive – Eliminated by apoptosis (clonal deletion) © 2013 Pearson Education, Inc. Seeding Secondary Lymphoid Organs and Circulation • Immunocompetent B and T cells not yet exposed to antigen called naive • Move from primary lymphoid organs (bone marrow and thymus) to "seed" secondary lymphoid organs (lymph nodes, spleen, etc.) © 2013 Pearson Education, Inc. Antigen Encounter and Activation • Clonal selection – Naive lymphocyte's first encounter with antigen selected for further development – If correct signals present, lymphocyte will complete its differentiation © 2013 Pearson Education, Inc. Proliferation and Differentiation • Activated lymphocyte proliferates exact clones • Most clones effector cells that fight infections • A few remain as memory cells – Able to respond to same antigen more quickly second time • B and T memory cells and effector T cells circulate continuously © 2013 Pearson Education, Inc. Antigen Receptor Diversity • Genes, not antigens, determine which foreign substances immune system will recognize – Immune cell receptors result of acquired knowledge of microbes likely in environment • Lymphocytes make a billion or more different types of antigen receptors – Coded for by ~1,000 genes – Gene segments are shuffled by somatic recombination © 2013 Pearson Education, Inc. Table 21.3 Overview of B and T Lymphocytes © 2013 Pearson Education, Inc. Antigen-presenting Cells (APCs) • Engulf antigens • Present fragments of antigens to T cells for recognition • Major types – Dendritic cells in connective tissues and epidermis – Macrophages in connective tissues and lymphoid organs – B cells © 2013 Pearson Education, Inc. Dendritic Cells and Macrophages • Dendritic cells phagocytize pathogens, enter lymphatics to present antigens to T cells in lymph node – Most effective antigen presenter known – Key link between innate and adaptive immunity • Macrophages widespread in lymphoid organs and connective tissues – Present antigens to T cells to activate themselves into voracious phagocytes that secrete bactericidal chemicals © 2013 Pearson Education, Inc. Adaptive Immunity: Summary • Uses lymphocytes, APCs, and specific molecules to identify and destroy nonself substances • Depends upon ability of its cells to – Recognize antigens by binding to them – Communicate with one another so that whole system mounts specific response © 2013 Pearson Education, Inc. Activation and Differentiation of B Cells • B cell activated when antigens bind to its surface receptors • Causes proliferation and differentiation into effector cells (mostly plasma cells, a few memory B cells) © 2013 Pearson Education, Inc. Fate of the Clones • Most clone cells become plasma cells – Secrete specific antibodies at rate of 2000 molecules per second for four to five days, then die – Antibodies circulate in blood or lymph • Bind to free antigens and mark for destruction by innate or adaptive mechanisms © 2013 Pearson Education, Inc. Fate of the Clones • Clone cells that do not become plasma cells become memory B cells – Provide immunological memory – Allow stronger, faster response to future exposures to same antigen © 2013 Pearson Education, Inc. Figure 21.11a Clonal selection of a B cell. Adaptive defenses Humoral immunity Primary response (initial encounter with antigen) Activated B cells Plasma cells (effector B cells) Secreted antibody molecules © 2013 Pearson Education, Inc. Proliferation to form a clone Antigen Antigen binding to a receptor on a specific B lymphocyte (B lymphocytes with noncomplementary receptors remain inactive) Memory B cell— primed to respond to same antigen Immunological Memory • Primary immune response – Cell proliferation and differentiation upon first antigen exposure – Lag period: three to six days – Peak levels of plasma antibody are reached in 10 days – Antibody levels then decline © 2013 Pearson Education, Inc. Immunological Memory • Secondary immune response – Re-exposure to same antigen gives faster, more prolonged, more effective response • Sensitized memory cells respond within hours • Antibody levels peak in two to three days at much higher levels • Antibodies bind with greater affinity • Antibody level can remain high for weeks to months © 2013 Pearson Education, Inc. Figure 21.11 Clonal selection of a B cell. Adaptive defenses Humoral immunity Primary response (initial encounter with antigen) Activated B cells Proliferation to form a clone Plasma cells (effector B cells) Memory B cell— primed to respond to same antigen Secreted antibody molecules Secondary response (can be years later) Antigen Antigen binding to a receptor on a specific B lymphocyte (B lymphocytes with noncomplementary receptors remain inactive) Clone of cells identical to ancestral cells Subsequent challenge by same antigen results in more rapid response Plasma cells Secreted antibody molecules © 2013 Pearson Education, Inc. Memory B cells Figure 21.12 Primary and secondary humoral responses. Secondary immune response to antigen A is faster and larger; primary immune response to antigen B is similar to that for antigen A. Antibody titer (antibody concentration) in plasma (arbitrary units) Primary immune response to antigen A occurs after a delay. 104 103 102 101 100 0 7 First exposure to antigen A © 2013 Pearson Education, Inc. AntiBodies to B AntiBodies to A 14 21 28 35 42 Second exposure to antigen A; first exposure to antigen B Time (days) 49 56 Active Humoral Immunity • When B cells encounter antigens and produce specific antibodies against them • Two types of active humoral immunity: – Naturally acquired—response to bacterial or viral infection – Artificially acquired—response to vaccine of dead or attenuated pathogens © 2013 Pearson Education, Inc. Active Humoral Immunity • Vaccines – Most of dead or attenuated pathogens – Spare us symptoms of primary response – Provide antigenic determinants that are immunogenic and reactive © 2013 Pearson Education, Inc. Passive Humoral Immunity • Readymade antibodies introduced into body • B cells are not challenged by antigens • Immunological memory does not occur • Protection ends when antibodies degrade © 2013 Pearson Education, Inc. Passive Humoral Immunity • Two types 1. Naturally acquired—antibodies delivered to fetus via placenta or to infant through milk 2. Artificially acquired—injection of serum, such as gamma globulin • © 2013 Pearson Education, Inc. Protection immediate but ends when antibodies naturally degrade in body Figure 21.13 Active and passive humoral immunity. Humoral immunity Active Naturally acquired Infection; contact with pathogen © 2013 Pearson Education, Inc. Artificially acquired Vaccine; dead or attenuated pathogens Passive Naturally acquired Antibodies passed from mother to fetus via placenta; or to infant in her milk Artificially acquired Injection of exogenous antibodies (gamma globulin)