microbiology ch 16 lecture_presentation

Chapter Title

Adaptive Immunity16

PowerPoint Lecture Presentations prepared by Mindy Miller-Kittrell, North Carolina State UniversityC H A P T E R 2015 Pearson Education, Inc.

2015 Pearson Education, Inc.

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Overview of Adaptive ImmunityAdaptive immunity is the body's ability to recognize and defend itself against distinct invaders and their productsFive attributes of adaptive immunitySpecificityInducibilityClonalityUnresponsiveness to selfMemory

2015 Pearson Education, Inc.2

Overview of Adaptive ImmunityInvolves activity of lymphocytesTwo main types of lymphocytesB lymphocytes (B cells)Mature in the bone marrowT lymphocytes (T cells)Mature in the thymusTwo types of adaptive immune responsesCell-mediated immune responsesAntibody immune responses


LymphocyteRed blood cell

Figure 16.1 Lymphocytes play a central role in adaptive immunity.


Host Defenses: The Big Picture


Cell-Mediated Immunity: Overview


Humoral Immunity: Overview


Overview of Adaptive ImmunityTell Me WhyWhy are the activities of B and T cells called adaptive?


Elements of Adaptive ImmunityThe Tissues and Organs of the Lymphatic SystemComposed of lymphatic vessels and lymphatic cells, tissues, and organsScreen the tissues of the body for foreign antigens


Elements of Adaptive ImmunityThe Tissues and Organs of the Lymphatic SystemThe lymphatic vessels and the flow of lymphLymphatic vesselsOne-way system that conducts lymph from tissues and returns it to the circulatory systemLymphLiquid with composition similar to blood plasmaArises from fluid leaked from blood vessels into surrounding tissues


BloodcapillaryFrom heartTissue cellIntercellularfluidLymphto heartvia lymphaticvesselsGap in wallValveLymphatic capillaryTo heartAfferentlymphatic vesselMedullaVeinArteryEfferentlymphaticvesselCapsulePrimary follicleLymphatic noduleValve(prevents backflow)CortexTonsilsCervical lymph nodeLymphatic ductsThymus glandAxillary lymphnodeHeartBreast lymphaticsSpleenAbdominallymph nodeIntestinesPeyer's patches inintestinal wallPart of mucosa-associated lymphoidtissue (MALT)AppendixRed bonemarrowInguinal lymphnodeLymphaticvessel

Figure 16.2 The lymphatic system.


Elements of Adaptive ImmunityThe Tissues and Organs of the Lymphatic SystemLymphoid organsPrimary lymphoid organsRed bone marrowThymusSecondary lymphoid organsLymph nodesSpleenTonsilsMucosa-associated lymphoid tissue (MALT)


Elements of Adaptive ImmunityAntigensProperties of antigensMolecules that the body recognizes as foreign and worthy of attackRecognized by three-dimensional regions called epitopes on antigensLarge foreign macromolecules make the best antigensInclude various bacterial components as well as proteins of viruses, fungi, and protozoaFood and dust can also contain antigenic particles


Epitopes(antigenicdeterminants)CytoplasmicmembraneCytoplasmAntigenEpitopes (antigenic determinants)Nucleus

Figure 16.3a Antigens, molecules that provoke a specific immune response.


ExtracellularmicrobesExogenousantigensEndogenousantigensIntracellularvirusVirallyinfectedcellAutoantigens(normal cell antigens)Normal(uninfected)cellExogenous antigensEndogenous antigensAutoantigens

Figure 16.3b-d Antigens, molecules that provoke a specific immune response.


Elements of Adaptive ImmunityT Lymphocytes (T Cells) and Preparation for an Adaptive Immune ResponseT cells act primarily against cells that harbor intracellular pathogensSome T cells act against body cells that produce abnormal cell-surface proteinsCirculate in the lymph and blood Migrate to the lymph nodes, spleen, and Peyer's patches Have T cell receptors (TCRs) on their cytoplasmic membrane


Elements of Adaptive ImmunityT Lymphocytes (T Cells) and Preparation for an Adaptive Immune ResponseSpecificity of the T cell receptor (TCR)Each cell's TCR has a specific antigen-binding siteTCRs do not recognize epitopes directlyTCRs bind only epitopes associated with an MHC protein


Antigen-bindingsiteVariableregionsConstantregionsCarbohydrateT cell receptor(TCR)Cytoplasmicmembraneof T cellCytoplasm

Figure 16.4 A T cell receptor (TCR).


Preparation for an Adaptive Immune ResponseT Lymphocytes (T Cells) and Preparation for an Adaptive Immune ResponseThe Roles of the Major Histocompatibility Complex and Antigen-Presenting CellsGroup of antigens first identified in graft patientsImportant in determining compatibility of tissues for tissue graftingMajor histocompatibility antigens are glycoproteins found in the membranes of most cells of vertebrate animalsHold and position antigenic determinants for presentation to T cells


Preparation for an Adaptive Immune ResponseT Lymphocytes (T Cells) and Preparation for an Adaptive Immune ResponseThe Roles of the Major Histocompatibility Complex and Antigen-Presenting CellsAntigens bind in the antigen-binding groove of MHC moleculesTwo classes of MHC proteinsMHC class IPresent on all cells except red blood cellsMHC class IIPresent on antigen-presenting cells (APCs)Include B cells, macrophages, and dendritic cells


Antigen-binding sites(grooves)Class I MHCon everynucleatedcellClass II MHCon B cell or otherantigen-presentingcell (APC)CytoplasmicmembraneCytoplasm

Figure 16.5 The two classes of major histocompatibility complex (MHC) proteins.


Dendrites

Figure 16.6 Dendritic cells.


Preparation for an Adaptive Immune ResponseT Lymphocytes (T Cells) and Preparation for an Adaptive Immune ResponseAntigen processingAntigens processed for MHC proteins to display epitopesDifferent processes for endogenous and exogenous antigens


Antigen Processing and Presentation: Overview


Polypeptideis catabolized.EpitopesMHC I proteinin membraneof endoplasmicreticulumLumen ofendoplasmicreticulumEpitopes are loaded onto complementary MHC I proteins in the ER.MHC I proteinepitope complexGolgi bodies package MHC I proteinepitopecomplexes into vesicles.MHC I proteinepitopecomplexes oncell surfaceCytoplasmicmembraneMHC I proteinepitope complexes are displayedon cytoplasmic membranes of all nucleated cells.54321Vesicles fuse with cytoplasmic membrane.

Figure 16.7 The processing of T-dependent endogenous antigens.


Phagocytosisby APCExogenouspathogenwith antigensMHC II protein inmembrane of vesicleEpitopes inphagolysosomeMHC II proteinepitope complexVesicles fuse and epitopes bind tocomplementary MHC II molecules.Vesicle fuses with cytoplasmic membrane.MHC II proteinepitopecomplexes oncell surfaceCytoplasmicmembraneMHC II proteinepitope complexes are displayedon cytoplasmic membranes of antigen-presenting cell.

1234Figure 16.8 The processing of T-dependent exogenous antigens.


Antigen Processing and Presentation: Steps


Antigen Processing and Presentation: MHC


Elements of Adaptive ImmunityT Lymphocytes (T Cells) and Preparation for an Adaptive Immune ResponseTypes of T lymphocytesBased on surface glycoproteins and characteristic functionsCytotoxic T lymphocyteDirectly kills other cellsHelper T lymphocyteHelps regulate B cells and cytotoxic T cellsIncludes type 1 and type 2 helper T cellsRegulatory T lymphocyteRepresses adaptive immune responses


Cell-Mediated Immunity: Helper T Cells



Elements of Adaptive ImmunityT Lymphocytes (T Cells) and Preparation for an Adaptive Immune ResponseClonal deletionVital that immune responses not be directed against autoantigensBody eliminates self-reactive lymphocytesLymphocytes that react to autoantigens undergo apoptosis


Figure 16.9 Clonal deletion of T cells.

Stem cell(in red bone marrow)ThymusT cellsTCRs withdifferently shapedbinding sitesMHCEpitopeThymuscellsRecognizeMHC?ThymuscellsNoYesReceive survivalsignalRecognizeMHC-autoantigen?ApoptosisNoYesFewMostRepertoire ofimmature Tc cellsRegulatoryT cell (Tr)Apoptosis

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Elements of Adaptive ImmunityB Lymphocytes (B Cells) and AntibodiesFound primarily in the spleen, lymph nodes, and MALTSmall percentage of B cells circulate in the bloodMajor function is the secretion of antibodies


Elements of Adaptive ImmunityB Lymphocytes (B Cells) and AntibodiesSpecificity of the B cell receptor (BCR)Each B lymphocyte has multiple copies of the B cell receptor (BCR)Each B cell generates a single BCRTwo variable regions of the BCR form the antigen-binding sitesEach BCR recognizes only one epitopeThe entire repertoire of an individual's BCRs is capable of recognizing millions of different epitopes


EpitopeAntigen-bindingsitesHeavy chainLight chainVariableregionDisulfide bondCytoplasmicmembrane ofB lymphocyteCytoplasmTransmembraneportion of BCR

SSSSSSSS

Figure 16.10 B cell receptor (BCR).


Elements of Adaptive ImmunityB Lymphocytes (B Cells) and AntibodiesSpecificity and antibody structureAntibodies are immunoglobulins similar to BCRsSecreted by activated B cells called plasma cellsHave antigen-binding sites and antigen specificity identical to the BCR of the activated B cell


Light chainArm (Fab)HingeStem (Fc)Antigen-binding sitesVariable regionof heavy chainVariable regionof light chainConstant regionof light chainConstant regionof heavy chainArm (Fab)HingeStem (Fc)

SSSSSSSSHeavy chains

Figure 16.11 Basic antibody structure.


Elements of Adaptive ImmunityB Lymphocytes (B Cells) and AntibodiesAntibody functionAntigen-binding sites are complementary to epitopesAntibodies function in several waysActivation of complement and inflammationNeutralizationOpsonizationKilling by oxidationAgglutinationAntibody-dependent cellular cytotoxicity (ADCC)


AdhesinproteinsBacteriumToxinVirusNeutralizationAgglutinationPseudopodof phagocyteNK lymphocyteFcreceptor proteinPerforin allows granzymeto enter, triggers apoptosisand lysisAntibody-dependent cellularcytotoxicity (ADCC)Bacteria dieOxidationOpsonizationFcreceptor protein

Figure 16.12 Five functions of antibodies.


Humoral Immunity: Antibody Function


Elements of Adaptive ImmunityB Lymphocytes (B Cells) and AntibodiesClasses of antibodiesThreats confronting the immune system are variableAntibody class involved in the immune response variesType of antigenPortal of entryAntibody function neededFive different classes of antibodies


Elements of Adaptive ImmunityB Lymphocytes (B Cells) and AntibodiesClasses of antibodiesIgM first antibody producedIgG most common and longest-lasting antibodyIgA associated with body secretionsIgE involved in response to parasitic infections and allergiesIgD exact function is not known



Elements of Adaptive ImmunityB Lymphocytes (B Cells) and AntibodiesClonal deletion of B cellsOccurs in the bone marrowSimilar to deletion of T cellsSelf-reactive B cells may become inactive or change their BCR


Stem cell(in red bone marrow)B cellsCell withautoantigensBCRs withdifferentlyshapedbinding sitesCell withautoantigensApoptosisBlood vesselTo spleen1234

Figure 16.13 Clonal deletion of B cells.


Elements of Adaptive ImmunityImmune Response CytokinesSoluble regulatory proteins that act as intercellular signalsCytokines secreted by various leukocytesCytokine network Complex web of signals among cells of the immune system


Elements of Adaptive ImmunityImmune System CytokinesInterleukins (ILs)Signal among leukocytesInterferons (IFNs)Antiviral proteins that may act as cytokinesGrowth factorsProteins that stimulate stem cells to divideTumor necrosis factor (TNF)Secreted by macrophages and T cells to kill tumor cells and regulate immune responses and inflammationChemokinesChemotactic cytokines that signal leukocytes to move



Elements of Adaptive ImmunityTell Me WhyWhy are exogenous epitopes processed in vesicles instead of in endoplasmic reticulum, as endogenous epitopes are?


Cell-Mediated Immune ResponsesRespond to intracellular pathogens and abnormal body cellsCommon intracellular pathogens are virusesThe response is also effective against cancer cells, intracellular protozoa, and intracellular bacteria


Cell-Mediated Immune ResponsesActivation of Cytotoxic T Cell Clones and Their FunctionsAdaptive immune responses initiated in lymphoid organsSteps involved in activation of cytotoxic T cellsAntigen presentationHelper T cell differentiationClonal expansionSelf-stimulation


Figure 16.14 Activation of a clone of cytotoxic T (Tc) cells.

Antigen presentationMHC IIEpitopeTCRThcellTh differentiationTh1 cellIL-2RIL-2IL-2RIL-12DCIL-2ActiveTc cellsMHC IInactiveTc cellIL-2 receptor(IL-2R)Clonal expansionMemoryT cellSelf-stimulationIL-2IL-2Dendritic cellMHC ICD8EpitopeTCRTc cellImmunological synapse

Active Tc cells1234


Activecytotoxic T(Tc) cellTCRViral epitopeMHC IproteinVirallyinfected cellIntracellularvirus

CD8Figure 16.15a A cell-mediated immune response.


Cell-Mediated Immune ResponsesActivation of Cytotoxic T Cell Clones and Their FunctionsCytotoxic T cells kills their targets by two pathwaysPerforin-granzyme pathwayInvolves synthesis of killing proteinsCD95 pathwayMediated by a glycoprotein on the body's cells


Tc cellPerforinGranzymePerforincomplex (pore)Granzymes activateapoptotic enzymesInactiveapoptoticenzymesActive enzymes induce apoptosisVirally infected cellTc cellCD95LCD95Enzymaticportion of CD95becomes activeInactiveapoptoticenzymesActive enzymes induceapoptosisVirally infected cell

Figure 16.15b-c A cell-mediated immune response.


Cell-Mediated Immunity: Cytotoxic T Cells


Cell-Mediated Immune ResponsesMemory T CellsSome activated T cells become memory T cellsPersist for months or years in lymphoid tissuesImmediately functional upon subsequent contacts with epitope-MHC complex specific to its TCRMemory response is more effective than the primary response


Cell-Mediated Immune ResponsesT Cell RegulationRegulation needed to prevent T cell response to autoantigensT cells require additional signals from an antigen-presenting cellInteraction of the T cell and antigen-presenting cell stimulates the T cell to respond to the antigenRegulatory T cells also moderate cytotoxic T cell activity


Cell-Mediated Immune ResponsesTell Me WhyWhy did scientists give the name perforin to a molecule secreted by Tc cells?


Antibody Immune ResponsesAntibody immune responses mounted against exogenous pathogens and toxinsActivates only in response to specific pathogens


Antibody Immune ResponsesInducement of T-Independent Antibody ImmunityT-independent antigensHave many identical, repeating epitopesInduce antibody response without assistance of helper T cells


BCRsB cellPolysaccharide withrepeating subunitsPlasmacellsAntibodies

Figure 16.16 The effects of the binding of a T-independent antigen by a B cell.


Rough endoplasmicreticulumNucleusGolgi body

Figure 16.17 A plasma cell.


Antibody Immune ResponsesInducement of T-Independent Antibody ImmunityT-independent immunity is weak, disappears quickly, and induces little memoryT-independent responses are stunted in childrenCan cause childhood diseases that are rare in adults


Antibody Immune ResponsesInducement of T-Dependent Antibody Immunity with Clonal SelectionT-dependent antigensAre small and lack repetitive epitopesImmune responses against them require the assistance of helper T cellsTh2 cells induce B cells that recognize the same antigen


Repertoire of Th cells (CD4 cells)CD4TCRsAPC presentsantigen to Th cellsfor Th activationand cloning. APCTh cellTCREpitopeMHC IICD4CD28CD80(orCD86)APCTh cell clonesTh cell differentiatesinto Th2 cell.CCR3CCR4Th2 cellIL-4MHC IIproteinsRepertoire of B cellsTh2 cellTCREpitopeMHC IICD40CD40LCD4Th2 cellactivates B cell.Clone ofplasma cellsAntibodiesMemory B cellsTh2 cellB cell1234

IL-4

Figure 16.18 A T-dependent antibody immune response.


Humoral Immunity: Clonal Selection and Expansion


Antibody Immune ResponsesInducement of T-Dependent Antibody Immunity with Clonal SelectionPlasma cellsMajority of cells produced during B cell proliferationOnly secrete antibody molecules that are complementary to the specific antigenShort-lived cells that die within a few days of activationTheir antibodies and progeny can persist


Antibody Immune ResponsesMemory B Cells and the Establishment of Immunological MemoryMemory B cellsProduced by B cell proliferation but do not secrete antibodiesHave BCRs complementary to the epitope that triggered their productionLong-lived cells that persist in the lymphoid tissueInitiates antibody production if antigen is encountered again


Figure 16.19 The production of primary and secondary antibody immune responses.


Humoral Immunity: Primary Immune Response


Humoral Immunity: Secondary Immune Response


Host Defenses: The Big Picture


Antibody Immune ResponsesTell Me WhyPlasma cells are vital for protection against infection, but memory B cells are not. Why not?


Types of Acquired ImmunitySpecific immunity acquired during an individual's lifeTwo typesNaturally acquiredResponse against antigens encountered in daily lifeArtificially acquiredResponse to antigens introduced via a vaccineDistinguished as either active or passive



Types of Acquired ImmunityTell Me WhyWhy is passive immunity effective more quickly than active immunity?


Immunology
