Welcome to Microbiology 130

Chapter 16Adaptive ImmunityThird Line of DefenseIs called specific or acquired immunityThe bodys ability to recognize and defend itself against distinct invaders and their productsA smart system whose memory allows it to respond rapidly to a second encounter with a pathogen2Elements of Adaptive ImmunityIs acquired over timeAntigens trigger specific immune responsesVarious cells, tissues, and organs are part of specific immunityIncludes B and T lymphocytes3Lymphatic SystemScreens the tissues of the body for foreign antigensComposed of lymphatic fluid, vessels and lymphatic cellsLymphatic VesselsForm a one-way system that conducts lymph from local tissues and returns it to the circulatory systemLymph is a liquid with similar composition to blood plasma that arises from fluid leaked from blood vessels into surrounding tissues5 2014 Pearson Education, Inc.Figure 16.2 The lymphatic system.

TonsilsCervical lymph nodeLymphatic ductsThymus glandAxillary lymphnodeHeartBreast lymphaticsSpleenAbdominallymph nodeIntestinesPeyers patches inintestinal wallAppendixRed bonemarrowInguinal lymphnodeLymphaticvesselPart of mucosa-associated lymphoidtissue (MALT)BloodcapillaryFrom heartTissue cellIntercellularfluidLymphto heartvia lymphaticvesselsGap in wallValveLymphatic capillaryTo heartAfferentlymphatic vesselMedullaVeinArteryEfferentlymphaticvesselCapsulePrimary follicleLymphatic noduleValve(prevents backflow)Cortex6Lymph NodesHouse leukocytes that recognize and attack foreign antigens present in the lymphConcentrated in the cervical (neck), inguinal (groin), axillary (armpit), and abdominal regionsReceives lymph from afferent lymphatic vessels and drains lymph into efferent lymphatic vessels7Other Lymphoid Tissues and OrgansSpleenSimilar in structure and function to the lymph nodesFilters bacteria, viruses, toxins, and other foreign matter from the bloodTonsils and mucosa-associated lymphoid tissue (MALT)Physically trap foreign particles and microbes that are ingested or inhaledMALT includes the appendix, lymphoid tissue of the respiratory tract, and Peyers patches in the wall of the small intestine8AntigensMolecules that trigger a specific immune responseInclude components of bacterial cell walls, capsules, pili, and flagella, as well as proteins of viruses, fungi, and protozoaFood and dust can also contain antigenic particlesEnter the body by various methods:Through breaks in the skin and mucous membranesDirect injection, as with a bite or needleThrough ingestion or inhalation9Figure 16.1

The Nature of AntigensWhy are B cells called B cells?

11Figure 16.3a

Figure 16.3b

The production,maturation,and deploymentof lymphocytesB LymphocytesArise and mature in the bone marrow Found primarily in the Secondary lymphoid tissue: spleen, lymph nodes, bone marrow, and Peyers patchesSmall percentage of B cells circulate in the bloodMajor function is the differentiation into plasma cells which secrete antibodies14AntibodiesAlso called immunoglobulins (Ig)Soluble, glycoprotein molecules that bind antigenSecreted by plasma cells, which are activated and differentiated B cells Considered part of the humoral immune response since bodily fluids such as lymph and blood were once called humors15Figure 16.5

Basic structureof an antibody16 2014 Pearson Education, Inc.Figure 16.5b Basic antibody structure.

Stem (Fc)HingeArm (Fab)17Antibody FunctionsAntigen-binding sites are complementary to antigenic determinants (epitopes)Due to the close fit, can form strong, noncovalent interactionsHydrogen bonds, ionic attractions, and hydrophobic interactions are involvedNeutralization (both viruses and toxins)OpsonizationAgglutinationActivation of complement

18Figure 16.6 Five functions of antibodies.

BacteriumAdhesinproteinsVirusToxinNeutralizationAgglutinationNK lymphocyte Fc receptor proteinPerforin allows granzymeto enter, triggers apoptosisand lysisAntibody-dependent cellularcytotoxicity (ADCC)Pseudopodof phagocyte Fc receptor proteinOpsonizationOxidationBacteria die19Classes of AntibodiesA single type of antibody is not sufficient for the multiple types of invaders to the bodyThe class involved in the immune response depends on the type of foreign antigen, the portal of entry, and the antibody function needed5 different classes of antibodies20

Table 16.1 Characteristics of the Five Classes of Antibodies21B Cell Receptor (BCR)Is an antibody that remains associated with the cytoplasmic membraneEach B lymphocyte has multiple copies of a single type of BCR (either IgM or IgD)Antigen binding site is identical to that of the secreted antibody for that particular cellThe randomly chosen V, D, and J regions and how they are put together determines the BCR specificity22B Cell Receptor (BCR)Each BCR on an individual cell is complementary to only one antigenic determinantThe BCRs on all of an individuals B cells are capable of recognizing millions of different antigenic determinants

23T LymphocytesProduced in the red bone marrow and mature in the thymus (unique TCR made)Circulate in the lymph and blood and migrate to secondary lymphoid tissue: lymph nodes, spleen, and Peyers patchesPart of the cell-mediated immune response because they act directly against various antigens Endogenous invadersMany of the bodys cells that harbor intracellular pathogensAbnormal body cells such as cancer cells that produce abnormal cell surface proteins24 2014 Pearson Education, Inc.Figure 16.7 A T cell receptor (TCR).

VariableregionsConstantregionsAntigen-bindingsiteCarbohydrateCytoplasmicmembraneof T cellT cell receptorCytoplasm(TCR)25T LymphocytesAccount for 70-85% of all lymphocytes in the bloodImmunologists recognize types of T cells based on surface glycoproteins and characteristic functions3 types:Cytotoxic T cellsHelper T cellsRegulatory T cells26Cytotoxic T cells (TC Cells)Distinguished by the CD8 cell-surface glycoproteinDirectly kill certain cellsCells infected with viruses and other intracellular pathogensAbnormal cells, such as cancer cells27Helper T Cells (TH Cells)Distinguished by the CD4 cell-surface glycoproteinFunction to help regulate the activities of B cells and cytotoxic T cells during an immune responseSecrete various soluble protein messengers, called cytokines, that determine which immune response will be activatedType 1 helper T cells (Th1 cells): assist Tc cells, and stimulate and regulate innate immunityType 2 helper T cells (Th2 cells): assist B cellsConductors of your immunological orchestra28Regulatory T CellsPreviously known as suppressor T cellsRepress adaptive immune responses and prevent autoimmune diseasesDistinguished by CD4 and CD25 cell-surface glycoproteinsActivated by contact with other immune cells and secrete cytokines29Lymphocyte Editing by Clonal DeletionVital that immune responses not be directed against self (autoantigens)Body edits lymphocytes (via apoptosis) to eliminate any self-reactive cellsOccurs in the thymus for T cellsOccurs in the bone marrow for B cellsEnd result: surviving lymphocytes respond only to foreign antigens30

Fig. 16-08Stem cell(in red bone marrow)T cellsThymuscellsTCRsMHC IEpitopeRecognizeMHC I?ThymuscellsApoptosisMostFewYesYesNoNoRecognizeMHC-autoantigen?Receive survivalsignalApoptosisRepertoire ofimmature Tc cellsRegulatoryT cell (Tr)T cell ClonalDeletion31

Fig. 16-09Stem cell(in red bone marrow)B cellsBCRsCell withautoantigensCell withautoantigensApoptosisBlood vesselTo spleenB cell ClonalDeletion32CytokinesSoluble regulatory proteins (over 200 total) that act as intercellular signals when released from certain body cellsImmune system cytokines signal among various leukocytesThe complex web of signals among all the cell types of the immune system is referred to as the cytokine network33Cytokines of the Immune SystemInterleukins (ILs)- signal among leukocytesInterferons (IFNs)- antiviral proteins that may act as cytokinesGrowth factors- proteins that stimulate stem cells to divide, maintaining an adequate supply of leukocytesTumor necrosis factors (TNFs)- Secreted by macrophages and T cells to kill tumor cells and regulate immune responses and inflammationChemokines- signal leukocytes to go to a site of inflammation or infection and stimulate other leukocytes34Major Histocompatibility Complex (MHC)Important in determining the compatibility of tissues in successful graftsMHC class I antigens are glycoproteins found in the membranes of most all nucleated cells of vertebrate animalsFunction to hold a peptide fragment from an intracellular protein (endogenous antigen) for presentation to T cellsMHC class II antigens found only on B cells and APCsFunction to hold a peptide fragment from an extracellular protein (exogenous antigen) for presentation to T cells35Figure 16.10 The two classes of major histocompatibility complex (MHC) proteins.

CytoplasmicmembraneClass I MHCon everynucleatedcellClass II MHCon B cell or otherantigen-presentingcell (APC)CytoplasmAntigen-bindingsites (grooves)36

Fig. 16-11DendritesDendritic Cells:Professional APCs37Antigen ProcessingT-independent antigenLarge antigen molecules with readily accessible, repeating antigenic determinantsB cells can bind and respond to these directly without T cell cytokine helpStimulates B cells to differentiate into a plasma cell and produce antibodiesAntibodies produced are often IgM onlyRelatively uncommon38Antigen ProcessingT-dependent antigensSmaller antigens with less accessible antigenic determinantsB cells require involvement from helper T cells to respond to these antigensHelper T cells are assisted by antigen presenting cells that process the antigen and make the antigenic determinants accessible to T cellsProcessing is different based on whether the antigen is exogenous or endogenous39Processing of Endogenous AntigensIntracellular proteins are broken down into smaller peptide fragments by the proteosome; fragments transported into endoplasmic reticulum (ER)Each fragment binds to a class I MHC molecule located in the ERThe membrane is packaged into a vesicle by a Golgi body which is inserted into the cytoplasmic membrane so the antigen is displayed on the cells surface40

Fig. 16-12PolypeptideEpitopesMHC I proteinin membraneof endoplasmicreticulumLumen ofendoplasmicreticulumThe polypeptide is catabolized to yield epitopes,which are loaded onto complementary MHC Iproteins in the ER.MHC I proteinepitope complexMHC I proteinepitopecomplexes are packaged in vesicle.Vesicle fuses with cytoplasmic membrane.CytoplasmicmembraneMHC I proteinepitopecomplexes oncell surfaceMHC I proteinepitope complexes displayed oncytoplasmic membranes of all nucleated cellsProcessing andPresentation ofEndogenous Antigen41Processing of Exogenous AntigensAPC internalizes the invading pathogen and enzymatically digests it into smaller antigenic fragments which are contained within an endosomeEndosome fuses with a vesicle containing class II MHC moleculesEach fragment binds to the antigen-binding groove of a complementary MHCII moleculeThe fused vesicle then inserts the MHCII-antigen complex into the cytoplasmic membrane so the antigen is presented on the outside of the cell42

Fig. 16-13Phagocytosisby APCExogenouspathogenwith antigensMHC II proteinepitope complexVesicles fuse and epitopes bind tocomplementary MHC II molecules.Vesicle fuses with cytoplasmic membrane.MHC II proteinepitopecomplexes oncell surfaceMHC II proteinepitope complexes displayed oncytoplasmic membranes of antigen-presenting cellCytoplasmicmembraneEpitopes inphagolysosomeMHC II protein inmembrane of vesicleProcessing andPresentation ofExogenous Antigen43Cell-Mediated Immune ResponseResponds to intracellular pathogens and abnormal body cellsThe most common intracellular pathogens are viruses but the response is also effective against intracellular bacteriaTriggered when antigenic determinants of the pathogen are displayed on the host cells surface 44

Fig. 16-14MHC II proteinEpitopeTCRThcellDCIL-12Antigen presentationTh differentiationIL-2Th1 cellClonal expansionIL-2 receptor(IL-2R)InactiveTc cellTc cellTCRCD8Immunological synapseEpitopeDendritic cellMHC IMemoryT cellSelf-stimulationActive Tc cellsIL-2IL-2ActiveTc cellsIL-2IL-2RIL-2RActivatinga Clone ofCytotoxicT cells 45

Fig. 16-15Activecytotoxic T(Tc) cellTCRViral epitopeMHC IproteinVirallyInfected cellIntracellularvirusCD8InactiveapoptoticenzymesPerforincomplex (pore)Virally infected cellGranzymes activateapoptotic enzymesActive apoptoticenzymes induceapoptosisTc cellTc cellPerforinGranzymeCD95LCD95InactiveapoptoticenzymesEnzymaticportion of CD95becomes activeActive apoptoticenzymes induceapoptosisVirally infected cellKilling Mechanisms ofActive Cytotoxic T cells 46Humoral Immune ResponseBody mounts humoral immune responses against exogenous pathogensComponents of a humoral immune responseB cell activation and clonal selectionAntibodiesMemory B cells and the establishment of immunological memory47

Fig. 16-18Repertoire of Th cells (CD4 cells)CD4CCR3TCRsAntigenpresentationfor Th activationand cloningTh cell clonesIL-4MHC IIproteinsClonalselectionof B cellDifferentiation ofTh into Th2 cellCCR4Th2 cellTh cellAPCTCRAPCCD4CD28CD80(orCD86)EpitopeMHC IITh2 cellTCREpitopeMHC IICD40LCD40Th2 cellB cellBCRActivation ofB cellRepertoire of B cellsIL-4Clone ofplasmacellsMemory B cellsAntibodiesEvents ina HumoralImmuneResponse 48Plasma CellsMake up the majority of cells produced during B cell proliferationEach plasma cell secretes antibody molecules complementary to one specific antigenic determinant. The class of antibody produced is determined by signals from T-helper cellsMany are short-lived cells that produce massive amounts of antibody (2,000 per sec) and then die within a few days. Others are longer-lived.49

Fig. 16-17Golgi bodyNucleusRough endoplasmicreticulumA PlasmaCell50Memory B CellsCells produced by B cell proliferation that do not secrete antibodiesCells that have BCRs complementary to the specific antigenic determinant that triggered their productionLong-lived cells that divide only a few times and then persist in the lymphoid tissueAre available to initiate antibody production more rapidly if the same antigen is encountered again51

The Humoral Immune Response52Acquired ImmunitySpecific immunity acquired during an individuals life2 types:Naturally acquired- immune response against antigens encountered in daily lifeArtificially acquired- response to antigens introduced via medical interventionFurther distinguished as either active or passiveActive- products made by the individual (humoral or cell-mediated responses)Passive- passively receive antibodies made by another individual53 2014 Pearson Education, Inc.Table 16.4 A Comparison of the Types of Acquired Immunity

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