Bài giảng Biology - Chapter 43: The Immune System

Chapter 43The Immune SystemOverview: Reconnaissance, Recognition, and ResponseAn animal must defend itselfFrom the many dangerous pathogens it may encounter in the environmentTwo major kinds of defense have evolved that counter these threatsInnate immunity and acquired immunityInnate immunityIs present before any exposure to pathogens and is effective from the time of birthInvolves nonspecific responses to pathogensFigure 43.13mAcquired immunity, also called adaptive immunityDevelops only after exposure to inducing agents such as microbes, toxins, or other foreign substancesInvolves a very specific response to pathogensA summary of innate and acquired immunityINNATE IMMUNITY Rapid responses to a broad range of microbesACQUIRED IMMUNITYSlower responses to specific microbesExternal defensesInternal defensesSkinMucous membranesSecretionsPhagocytic cellsAntimicrobial proteinsInflammatory responseNatural killer cellsHumoral response(antibodies)Cell-mediated response(cytotoxic lymphocytes)Invadingmicrobes(pathogens)Figure 43.2Concept 43.1: Innate immunity provides broad defenses against infectionA pathogen that successfully breaks through an animal’s external defensesSoon encounters several innate cellular and chemical mechanisms that impede its attack on the bodyExternal DefensesIntact skin and mucous membranesForm physical barriers that bar the entry of microorganisms and virusesCertain cells of the mucous membranes produce mucusA viscous fluid that traps microbes and other particlesIn the trachea, ciliated epithelial cellsSweep mucus and any entrapped microbes upward, preventing the microbes from entering the lungsFigure 43.310mSecretions of the skin and mucous membranesProvide an environment that is often hostile to microbesSecretions from the skinGive the skin a pH between 3 and 5, which is acidic enough to prevent colonization of many microbesAlso include proteins such as lysozyme, an enzyme that digests the cell walls of many bacteriaInternal Cellular and Chemical DefensesInternal cellular defensesDepend mainly on phagocytosisPhagocytes, types of white blood cellsIngest invading microorganismsInitiate the inflammatory responsePhagocytic CellsPhagocytes attach to their prey via surface receptorsAnd engulf them, forming a vacuole that fuses with a lysosomeFigure 43.4 Pseudopodiasurroundmicrobes.1 Microbesare engulfedinto cell.2 Vacuolecontainingmicrobesforms.3 Vacuoleand lysosomefuse.4 Toxiccompoundsand lysosomalenzymesdestroy microbes.5 Microbialdebris isreleased byexocytosis.6MicrobesMACROPHAGEVacuoleLysosomecontainingenzymesMacrophages, a specific type of phagocyteCan be found migrating through the bodyCan be found in various organs of the lymphatic systemAdenoidTonsilLymphnodesSpleenPeyer’s patches(small intestine)AppendixLymphaticvesselsMasses oflymphocytes andmacrophagesTissuecellsLymphaticvesselBloodcapillaryLymphaticcapillaryInterstitialfluidLymphnodeThe lymphatic systemPlays an active role in defending the body from pathogens Interstitial fluid bathing the tissues, along with the white blood cells in it, continually enters lymphatic capillaries.1Figure 43.5 Fluid inside thelymphatic capillaries,called lymph, flowsthrough lymphaticvessels throughoutthe body.2 Within lymph nodes,microbes and foreignparticles present in the circulating lymphencounter macro-phages, dendritic cells, and lymphocytes, which carry out various defensive actions.3 Lymphatic vesselsreturn lymph to theblood via two largeducts that drain intoveins near theshoulders.4Antimicrobial ProteinsNumerous proteins function in innate defenseBy attacking microbes directly of by impeding their reproductionAbout 30 proteins make up the complement systemWhich can cause lysis of invading cells and help trigger inflammationInterferonsProvide innate defense against viruses and help activate macrophagesInflammatory ResponseIn local inflammation, histamine and other chemicals released from injured cellsPromote changes in blood vessels that allow more fluid, more phagocytes, and antimicrobial proteins to enter the tissuesMajor events in the local inflammatory responseFigure 43.6PathogenPinMacrophageChemical signalsCapillaryPhagocytic cellsRed blood cellBloodclottingelementsBlood clotPhagocytosisFluid, antimicrobial proteins, and clotting elements move from the blood to the site.Clotting begins.2Chemical signals released by activated macrophages and mast cells at the injury site cause nearby capillaries to widen and become more permeable.1Chemokines released by various kinds of cells attract more phagocytic cells from the bloodto the injury site.3Neutrophils and macrophagesphagocytose pathogens and cell debris at the site, and the tissue heals.4Natural Killer CellsNatural killer (NK) cellsPatrol the body and attack virus-infected body cells and cancer cellsTrigger apoptosis in the cells they attackInvertebrate Immune MechanismsMany invertebrates defend themselves from infectionBy many of the same mechanisms in the vertebrate innate responseConcept 43.2: In acquired immunity, lymphocytes provide specific defenses against infectionAcquired immunityIs the body’s second major kind of defenseInvolves the activity of lymphocytesAntigen-binding sitesAntibody AAntigenAntibody BAntibody CEpitopes(antigenicdeterminants)An antigen is any foreign moleculeThat is specifically recognized by lymphocytes and elicits a response from themA lymphocyte actually recognizes and bindsTo just a small, accessible portion of the antigen called an epitopeFigure 43.7Antigen Recognition by LymphocytesThe vertebrate body is populated by two main types of lymphocytesB lymphocytes (B cells) and T lymphocytes (T cells)Which circulate through the bloodThe plasma membranes of both B cells and T cellsHave about 100,000 antigen receptor that all recognize the same epitopeB Cell Receptors for AntigensB cell receptorsBind to specific, intact antigensAre often called membrane antibodies or membrane immunoglobulinsFigure 43.8aAntigen-bindingsiteAntigen-binding siteDisulfidebridgeLightchainHeavy chainsCytoplasm of B cellVA B cell receptor consists of two identical heavy chains and two identical light chains linked by several disulfide bridges.(a)VariableregionsConstantregionsTransmembraneregionPlasmamembraneB cellVVCCCCVAntigen-Binding siteb chainDisulfide bridgea chainT cellA T cell receptor consists of one chain and one b chain linked by a disulfide bridge.(b)VariableregionsConstantregionsTransmembraneregionPlasmamembraneCytoplasm of T cellT Cell Receptors for Antigens and the Role of the MHCEach T cell receptorConsists of two different polypeptide chainsFigure 43.8bVVCCT cells bind to small fragments of antigensThat are bound to normal cell-surface proteins called MHC moleculesMHC moleculesAre encoded by a family of genes called the major histocompatibility complexInfected cells produce MHC moleculesWhich bind to antigen fragments and then are transported to the cell surface in a process called antigen presentationA nearby T cellCan then detect the antigen fragment displayed on the cell’s surfaceDepending on their sourcePeptide antigens are handled by different classes of MHC moleculesFigure 43.9aInfected cellAntigenfragmentClass I MHCmoleculeT cellreceptor(a) Cytotoxic T cellA fragment offoreign protein(antigen) inside thecell associates withan MHC moleculeand is transportedto the cell surface.1The combination ofMHC molecule andantigen is recognizedby a T cell, alerting itto the infection.212Class I MHC molecules, found on almost all nucleated cells of the bodyDisplay peptide antigens to cytotoxic T cellsClass II MHC molecules, located mainly on dendritic cells, macrophages, and B cellsDisplay antigens to helper T cells12Figure 43.9bMicrobeAntigen-presentingcellAntigenfragmentClass II MHCmoleculeT cellreceptorHelper T cellA fragment offoreign protein(antigen) inside thecell associates withan MHC moleculeand is transportedto the cell surface.1The combination ofMHC molecule andantigen is recognizedby a T cell, alerting itto the infection.2(b)Lymphocyte DevelopmentLymphocytesArise from stem cells in the bone marrowNewly formed lymphocytes are all alikeBut they later develop into B cells or T cells, depending on where they continue their maturationFigure 43.10Bone marrowLymphoidstem cellB cellBlood, lymph, and lymphoid tissues(lymph nodes, spleen, and others)T cellThymusGeneration of Lymphocyte Diversity by Gene RearrangementEarly in development, random, permanent gene rearrangementForms functional genes encoding the B or T cell antigen receptor chainsDNA ofundifferentiatedB cellDNA of differentiatedB cellpre-mRNAmRNACapB cellB cell receptorLight-chain polypeptideIntronIntronIntronVariableregionConstantregionV1V2V3V4–V39V40J1J2J3J4J5V1V2V3J5V3J5V3J5VCCCCCPoly (A)Figure 43.11 Deletion of DNA between a V segmentand J segment and joining of the segments1Immunoglobulin gene rearrangement Transcription of resulting permanently rearranged,functional gene2 RNA processing (removal of intron; addition of capand poly (A) tail)34TranslationTesting and Removal of Self-Reactive LymphocytesAs B and T cells are maturing in the bone and thymusTheir antigen receptors are tested for possible self-reactivityLymphocytes bearing receptors for antigens already present in the bodyAre destroyed by apoptosis or rendered nonfunctionalClonal Selection of LymphocytesIn a primary immune responseBinding of antigen to a mature lymphocyte induces the lymphocyte’s proliferation and differentiation, a process called clonal selectionClonal selection of B cellsGenerates a clone of short-lived activated effector cells and a clone of long-lived memory cellsFigure 43.12Antigen moleculesAntigenreceptorB cells thatdiffer inantigenspecificity AntibodymoleculesClone of memory cellsClone of plasma cellsAntigen moleculesbind to the antigenreceptors of only oneof the three B cellsshown.The selected B cellproliferates, forminga clone of identicalcells bearingreceptors for theselecting antigen.Some proliferatingcells develop intoshort-lived plasmacells that secreteantibodies specificfor the antigen.Some proliferating cellsdevelop into long-livedmemory cells that canrespond rapidly uponsubsequent exposureto the same antigen.In the secondary immune responseMemory cells facilitate a faster, more efficient responseAntibody concentration(arbitrary units)1041031021011000714212835424956Time (days)Figure 43.13Antibodiesto AAntibodiesto BPrimaryresponse toantigen Aproduces anti-bodies to A2Day 1: First exposure toantigen A1Day 28: Second exposureto antigen A; firstexposure to antigen B3Secondary response to anti-gen A produces antibodiesto A; primary response to anti-gen B produces antibodies to B4Concept 43.3: Humoral and cell-mediated immunity defend against different types of threatsAcquired immunity includes two branchesThe humoral immune response involves the activation and clonal selection of B cells, resulting in the production of secreted antibodiesThe cell-mediated immune response involves the activation and clonal selection of cytotoxic T cellsThe roles of the major participants in the acquired immune responseFigure 43.14Humoral immune responseCell-mediated immune responseFirst exposure to antigenIntact antigensAntigens engulfed and displayed by dendritic cellsAntigens displayedby infected cellsActivateActivateActivateGives rise toGives rise toGives rise toB cellHelperT cellCytotoxicT cellPlasmacellsMemoryB cellsActive and memory helperT cellsMemory cytotoxicT cellsActive  cytotoxicT cellsSecrete antibodies that defend againstpathogens and toxins in extracellular fluidDefend against infected cells, cancer cells, and transplanted tissuesSecretedcytokinesactivateHelper T Cells: A Response to Nearly All AntigensHelper T cells produce CD4, a surface proteinThat enhances their binding to class II MHC molecule–antigen complexes on antigen-presenting cellsActivation of the helper T cell then occursActivated helper T cellsSecrete several different cytokines that stimulate other lymphocytesThe role of helper T cells in acquired immunityFigure 43.15After a dendritic cell engulfs and degrades a bacterium, it displays bacterial antigen fragments (peptides) complexed with a class II MHC molecule on the cell surface. A specific helper T cell binds to the displayed complex via its TCR with the aid of CD4. This interaction promotes secretion of cytokines by the dendritic cell.Proliferation of the T cell, stimulatedby cytokines from both the dendritic cell and the T cell itself, gives rise toa clone of activated helper T cells(not shown), all with receptors for thesame MHC–antigen complex.The cells in this clonesecrete other cytokines that help activate B cellsand cytotoxic T cells.Cell-mediatedimmunity(attack oninfected cells)Humoralimmunity(secretion ofantibodies byplasma cells)DendriticcellDendriticcellBacteriumPeptide antigenClass II MHCmoleculeTCRCD4Helper T cellCytokinesCytotoxic T cellB cell123123Cytotoxic T Cells: A Response to Infected Cells and Cancer CellsCytotoxic T cells make CD8A surface protein that greatly enhances the interaction between a target cell and a cytotoxic T cellCytotoxic T cellsBind to infected cells, cancer cells, and transplanted tissuesBinding to a class I MHC complex on an infected body cellActivates a cytotoxic T cell and differentiates it into an active killerCytotoxic T cellPerforinGranzymesCD8TCRClass I MHCmoleculeTargetcellPeptideantigenPoreReleasedcytotoxicT cellApoptotictarget cellCancercellCytotoxicT cellA specific cytotoxic T cell binds to a class I MHC–antigen complex on a target cell via its TCR with the aid of CD8. This interaction, along with cytokines from helper T cells, leads to the activation of the cytotoxic cell.1The activated T cell releases perforin molecules, which form pores in the target cell membrane, and proteolytic enzymes (granzymes), which enter the target cell by endocytosis.2The granzymes initiate apoptosis within the target cells, leading to fragmentation of thenucleus, release of small apoptotic bodies, and eventual cell death. The released cytotoxic T cell can attack other target cells. 3123Figure 43.16The activated cytotoxic T cellSecretes proteins that destroy the infected target cellB Cells: A Response to Extracellular PathogensActivation of B cellsIs aided by cytokines and antigen binding to helper T cellsThe clonal selection of B cellsGenerates antibody-secreting plasma cells, the effector cells of humoral immunity213B cellBacteriumPeptide antigenClass II MHCmoleculeTCRHelper T cellCD4Activated helper T cellClone of memoryB cells CytokinesClone of plasma cellsSecreted antibodymolecules Endoplasmicreticulum of plasma cellMacrophageAfter a macrophage engulfs and degradesa bacterium, it displays a peptide antigencomplexed with a class II MHC molecule.A helper T cell that recognizes the displayed complex is activated with the aid of cytokines secreted from the macrophage, forming a clone of activated helper T cells (not shown).1A B cell that has taken up and degraded the same bacterium displays class II MHC–peptide antigen complexes. An activated helper T cellbearing receptors specific for the displayedantigen binds to the B cell. This interaction,with the aid of cytokines from the T cell,activates the B cell.2The activated B cell proliferatesand differentiates into memoryB cells and antibody-secreting plasma cells. The secreted antibodies are specific for the same bacterial antigen that initiated the response.3Figure 43.17Antibody ClassesThe five major classes of antibodies, or immunoglobulinsDiffer in their distributions and functions within the bodyThe five classes of immunoglobulinsFigure 43.18First Ig class produced after initial exposure to antigen; then its concentration in the blood declinesMost abundant Ig class in blood; also present in tissue fluidsOnly Ig class that crosses placenta, thus conferring passive immunity on fetusPromotes opsonization, neutralization, and agglutination of antigens; less effective in complement activation than IgM (see Figure 43.19)Present in secretions such as tears, saliva, mucus, and breast milkTriggers release from mast cells and basophils of histamine and other chemicals that cause allergic reactions (see Figure 43.20)Present primarily on surface of naive B cells that havenot been exposed to antigensIgM(pentamer)IgG(monomer)IgA(dimer)IgE(monomer)J chainSecretorycomponentJ chainTransmembraneregionIgD(monomer)Promotes neutralization and agglutination of antigens; very effective in complement activation (see Figure 43.19)Provides localized defense of mucous membranes byagglutination and neutralization of antigens (seeFigure 43.19)Presence in breast milk confers passive immunity onnursing infantActs as antigen receptor in antigen-stimulated proliferation and differentiation of B cells (clonal selection)Antibody-Mediated Disposal of AntigensThe binding of antibodies to antigensIs also the basis of several antigen disposal mechanismsLeads to elimination of microbes by phagocytosis and complement-mediated lysisAntibody-mediated mechanisms of antigen disposalBinding of antibodies to antigensinactivates antigens byViral neutralization(blocks binding to host)and opsonization (increasesphagocytosis)Agglutination ofantigen-bearing particles,such as microbesPrecipitation ofsoluble antigensActivation of complement systemand pore formationBacteriumVirusBacteriaSolubleantigensForeign cellComplementproteinsMAC PoreEnhancesPhagocytosisLeads toCell lysisMacrophageFigure 43.19Active and Passive ImmunizationActive immunityDevelops naturally in response to an infectionCan also develop following immunization, also called vaccinationIn immunizationA nonpathogenic form of a microbe or part of a microbe elicits an immune response to an immunological memory for that microbePassive immunity, which provides immediate, short-term protectionIs conferred naturally when IgG crosses the placenta from mother to fetus or when IgA passes from mother to infant in breast milkCan be conferred artificially by injecting antibodies into a nonimmune personConcept 43.4: The immune system’s ability to distinguish self from nonself limits tissue transplantationThe immune systemCan wage war against cells from other individualsTransplanted tissuesAre usually destroyed by the recipient’s immune systemBlood Groups and TransfusionsCertain antigens on red blood cells Determine whether a person has type A, B, AB, or O bloodAntibodies to nonself blood typesAlready exist in the bodyTransfusion with incompatible bloodLeads to destruction of the transfused cellsRecipient-donor combinationsCan be fatal or safeTable 43.1Another red blood cell antigen, the Rh factorCreates difficulties when an Rh-negative mother carries successive Rh-positive fetusesTissue and Organ TransplantsMHC moleculesAre responsible for stimulating the rejection of tissue grafts and organ transplantsThe chances of successful transplantation are increasedIf the donor and recipient MHC tissue types are well matchedIf the recipient is given immunosuppressive drugsLymphocytes in bone marrow transplantsMay cause a graft versus host reaction in recipientsConcept 43.5: Exaggerated, self-directed, or diminished immune responses can cause diseaseIf the delicate balance of the immune system is disruptedThe effects on the individual can range from minor to often fatal consequencesAllergiesAllergies are exaggerated (hypersensitive) responsesTo certain antigens called allergensIn localized allergies such as hay feverIgE antibodies produced after first exposure to an allergen attach to receptors on mast cellsThe next time the allergen enters the bodyIt binds to mast cell–associated IgE moleculesThe mast cells then release histamine and other mediatorsThat cause vascular changes and typical symptomsThe allergic responseFigure 43.20IgE antibodies produced in response to initial exposure to an allergen bind to receptors or mast cells.1On subsequent exposure to the same allergen, IgE molecules attached to a mast cell recog-nize and bind the allergen.2Degranulation of the cell,triggered by cross-linking of adjacent IgE molecules, releases histamine and other chemicals, leading to allergysymptoms.3123AllergenIgEHistamineGranuleMast cellAn acute allergic response sometimes leads to anaphylactic shockA whole-body, life-threatening reaction that can occur within seconds of exposure to an allergenAutoimmune DiseasesIn individuals with autoimmune diseasesThe immune system loses tolerance for self and turns against certain molecules of the bodyRheumatoid arthritisIs an autoimmune disease that leads to damage and painful inflammation of the cartilage and bone of jointsFigure 43.21Other examples of autoimmune diseases includeSystemic lupus erythematosusMultiple sclerosisInsulin-dependent diabetesImmunodeficiency DiseasesAn inborn or primary immunodeficiency Results from hereditary or congenital defects that prevent proper functioning of innate, humoral, and/or cell-mediated defensesAn acquired or secondary immunodeficiency Results from exposure to various chemical and biological agentsInborn (Primary) ImmunodeficienciesIn severe combined immunodeficiency (SCID)Both the humoral and cell-mediated branches of acquired immunity fail to functionAcquired (Secondary) ImmunodeficienciesAcquired immunodeficienciesRange from temporary states to chronic diseasesStress and the Immune SystemGrowing evidence showsThat physical and emotional stress can harm immunityAcquired Immunodeficiency Syndrome (AIDS)People with AIDSAre highly susceptible to opportunistic infections and cancers that take advantage of an immune system in collapseBecause AIDS arises from the loss of helper T cellsBoth humoral and cell-mediated immune responses are impairedThe loss of helper T cellsResults from infection by the human immunodeficiency virus (HIV)1µmFigure 43.22The spread of HIVHas become a worldwide problemThe best approach for slowing the spread of HIVIs educating people about the practices that transmit the virus