Chapter 22



Chapter 22 The Lymphatic System and ImmunityThe Lymphatic System and Immunity Learning Outcomes22-1Distinguish between innate (nonspecific) and adaptive (specific) defenses, and explain the role of lymphocytes in the immune response.22-2Identify the major components of the lymphatic system, describe the structure and functions of each component, and discuss the importance of lymphocytes.22-3List the body’s innate (nonspecific) defenses, and describe the components, mechanisms, and functions of each.The Lymphatic System and ImmunityLearning Outcomes22-4Define adaptive (specific) defenses, identify the forms and properties of immunity, and distinguish between cell-mediated (cellular) immunity and antibody-mediated (humoral) immunity.22-5Discuss the types of T cells and their roles in the immune response, and describe the mechanisms of T cell activation and differentiation.The Lymphatic System and ImmunityLearning Outcomes22-6Discuss the mechanisms of B cell activation and differentiation, describe the structure and function of antibodies, and explain the primary and secondary responses to antigen exposure.22-7Describe the development of immunocompetence, list and explain examples of immune disorders and allergies, and discuss the effects of stress on immune function.The Lymphatic System and ImmunityLearning Outcomes22-8Describe the effects of aging on the lymphatic system and the immune response.22-9 Give examples of interactions between the lymphatic system and other organ systems we have studied so far and explain how the nervous and endocrine systems influence the immune response.An Introduction to the Lymphatic System and ImmunityPathogens Microscopic organisms that cause disease:VirusesBacteriaFungiParasitesEach attacks in a specific way 22-1 Overview of the Lymphatic SystemThe Lymphatic SystemProtects us against diseaseLymphatic system cells respond to:Environmental pathogensToxinsAbnormal body cells, such as cancers 22-1 Overview of the Lymphatic SystemSpecific Defenses LymphocytesPart of the immune response Identify, attack, and develop immunityTo a specific pathogen22-1 Overview of the Lymphatic SystemThe Immune System ImmunityThe ability to resist infection and disease All body cells and tissues involved in production of immunityNot just lymphatic system 22-1 Overview of the Lymphatic SystemNonspecific Defenses Block or attack any potential infectious organismCannot distinguish one attack from another22-2 Structures of Body DefensesOrganization of the Lymphatic System LymphA fluid similar to plasma but does not have plasma proteins Lymphatic vessels (lymphatics)Carry lymph from peripheral tissues to the venous system Lymphoid tissues and lymphoid organs Lymphocytes, phagocytes, and other immune system cells22-2 Structures of Body DefensesFunction of the Lymphatic SystemTo produce, maintain, and distribute lymphocytesLymphocyte Production Lymphocytes are producedIn lymphoid tissues (e.g., tonsils)Lymphoid organs (e.g., spleen, thymus)In red bone marrowLymphocyte distribution Detects problemsTravels into site of injury or infection22-2 Structures of Body DefensesLymphocyte Circulation From blood to interstitial fluid through capillariesReturns to venous blood through lymphatic vesselsThe Circulation of FluidsFrom blood plasma to lymph and back to the venous systemTransports hormones, nutrients, and waste products22-2 Structures of Body DefensesLymphatic Vessels Are vessels that carry lymph Lymphatic system begins with smallest vesselsLymphatic capillaries (terminal lymphatics)22-2 Structures of Body DefensesLymphatic Capillaries Differ from blood capillaries in four waysStart as pockets rather than tubesHave larger diametersHave thinner wallsFlat or irregular outline in sectional view22-2 Structures of Body DefensesLymphatic Capillaries Endothelial cells loosely bound together with overlapOverlap acts as one-way valveAllows fluids, solutes, viruses, and bacteria to enterPrevents return to intercellular space22-2 Structures of Body DefensesLymph FlowFrom lymphatic capillaries to larger lymphatic vessels containing one-way valvesLymphatic vessels travel with veinsLactealsAre special lymphatic capillaries in small intestineTransport lipids from digestive tract22-2 Structures of Body DefensesLymphatic VesselsSuperficial lymphatics Deep lymphatics Are located in:SkinMucous membranesSerous membranes lining body cavities22-2 Structures of Body DefensesSuperficial and Deep Lymphatics The deep lymphatics Are larger vessels that accompany deep arteries and veinsSuperficial and deep lymphatics Join to form large lymphatic trunks Trunks empty into two major collecting vessels Thoracic duct Right lymphatic duct 22-2 Structures of Body DefensesMajor Lymph-Collecting VesselsThe base of the thoracic duct Expands into cisterna chyli Cisterna chyli receives lymph from:Right and left lumbar trunks Intestinal trunk22-2 Structures of Body DefensesThe Inferior Segment of Thoracic Duct Collects lymph from:Left bronchomediastinal trunkLeft subclavian trunkLeft jugular trunkEmpties into left subclavian vein22-2 Structures of Body DefensesThe Right Lymphatic Duct Collects lymph from:Right jugular trunkRight subclavian trunkRight bronchomediastinal trunk Empties into right subclavian vein22-2 Structures of Body DefensesLymphedema Blockage of lymph drainage from a limbCauses severe swellingInterferes with immune system function LymphocytesMake up 20–40 percent of circulating leukocytesMost are stored, not circulating22-2 Structures of Body DefensesTypes of Lymphocytes T cellsThymus-dependent B cellsBone marrow-derived NK cellsNatural killer cells22-2 Structures of Body DefensesT Cells Make up 80 percent of circulating lymphocytesMain Types of T CellsCytotoxic T (TC) cells Memory T cellsHelper T (TH) cellsSuppressor T (TS) cells22-2 Structures of Body DefensesCytotoxic T CellsAttack cells infected by virusesProduce cell-mediated immunityMemory T CellsFormed in response to foreign substanceRemain in body to give “immunity”Helper T CellsStimulate function of T cells and B cells22-2 Structures of Body DefensesSuppressor T CellsInhibit function of T cells and B cellsRegulatory T CellsAre helper and suppressor T cellsControl sensitivity of immune response22-2 Structures of Body DefensesOther T Cells Inflammatory T cells Suppressor/inducer T cellsB CellsMake up 10–15 percent of circulating lymphocytesDifferentiate (change) into plasma cellsPlasma cells Produce and secrete antibodies (immunoglobulin proteins) 22-2 Structures of Body DefensesAntigens Targets that identify any pathogen or foreign compoundImmunoglobulins (Antibodies)The binding of a specific antibody to its specific target antigen initiates antibody-mediated immunity22-2 Structures of Body DefensesAntibody-Mediated Immunity A chain of events that destroys the target compound or organismNatural Killer (NK) CellsAlso called large granular lymphocytes Make up 5–10 percent of circulating lymphocytesResponsible for immunological surveillanceAttack foreign cells, virus-infected cells, and cancer cells22-2 Structures of Body DefensesLymphocyte Distribution Tissues maintain different T cell and B cell populationsLymphocytes wander through tissuesEnter blood vessels or lymphatics for transport Can survive many years22-2 Structures of Body DefensesLymphocyte Production Also called lymphopoiesis, involves: Bone marrowThymusPeripheral lymphoid tissuesHemocytoblastsIn bone marrow, divide into two types of lymphoid stem cells22-2 Structures of Body DefensesLymphoid Stem Cells Group 1Remains in bone marrow and develop with help of stromal cellsProduces B cells and natural killer cellsGroup 2Migrates to thymusProduces T cells in environment isolated by blood–thymus barrier22-2 Structures of Body DefensesT Cells and B Cells Migrate throughout the bodyTo defend peripheral tissuesRetaining their ability to divideIs essential to immune system function22-2 Structures of Body DefensesDifferentiation B cells differentiateWith exposure to hormone called cytokine (interleukin-7)T cells differentiateWith exposure to several thymic hormones22-2 Structures of Body DefensesLymphoid TissuesConnective tissues dominated by lymphocytesLymphoid NodulesAreolar tissue with densely packed lymphocytesGerminal center contains dividing lymphocytes22-2 Structures of Body DefensesDistribution of Lymphoid Nodules Lymph nodesSpleenRespiratory tract (tonsils)Along digestive, urinary, and reproductive tracts22-2 Structures of Body DefensesMucosa-Associated Lymphoid Tissue (MALT) Lymphoid tissues associated with the digestive systemAggregated Lymphoid NodulesClustered deep to intestinal epithelial liningAppendix (Vermiform Appendix)Contains a mass of fused lymphoid nodules22-2 Structures of Body DefensesThe Five Tonsils In wall of pharynxLeft and right palatine tonsilsPharyngeal tonsil (adenoid)Two lingual tonsils22-2 Structures of Body DefensesLymphoid Organs Lymph nodesThymus Spleen Are separated from surrounding tissues by a fibrous connective tissue capsule22-2 Structures of Body DefensesLymph NodesTrabeculae Bundles of collagen fibers Extend from capsule into interior of lymph nodeHilumA shallow indentation where blood vessels and nerves reach the lymph node22-2 Structures of Body DefensesLymph NodesAfferent lymphaticsCarry lymphFrom peripheral tissues to lymph nodeEfferent lymphaticsLeave lymph node at hilum Carry lymph to venous circulation22-2 Structures of Body DefensesLymph FlowFlows through lymph node in a network of sinusesFrom subcapsular space Contains macrophages and dendritic cells Through outer cortex Contains B cells within germinal centersThrough deep cortex Dominated by T cellsThrough the core (medulla) Contains B cells and plasma cells, organized into medullary cordsFinally, into hilum and efferent lymphatics22-2 Structures of Body DefensesLymph Node Function A filterPurifies lymph before return to venous circulationRemoves:DebrisPathogens99 percent of antigens22-2 Structures of Body DefensesAntigen Presentation First step in immune responseExtracted antigens are “presented” to lymphocytesOr attached to dendritic cells to stimulate lymphocytes 22-2 Structures of Body DefensesLymphatic Functions Lymphoid tissues and lymph nodesDistributed to monitor peripheral infectionsRespond before infections reach vital organs of trunkLymph nodes of gut, trachea, lungs, and thoracic duct Protect against pathogens in digestive and respiratory systems22-2 Structures of Body DefensesLymph Nodes (Glands)Large lymph nodes at groin and base of neck Swell in response to inflammationLymphadenopathyChronic or excessive enlargement of lymph nodes May indicate infections, endocrine disorders, or cancer22-2 Structures of Body DefensesThe Thymus Located in mediastinumAtrophies after pubertyDiminishing effectiveness of immune systemDivisions of the ThymusThymus is divided into two thymic lobesSepta divide lobes into smaller lobules22-2 Structures of Body DefensesA Thymic Lobule Contains a dense outer cortex and a pale central medullaLymphocytesDivide in the cortexT cells migrate into medullaMature T cells leave thymus by medullary blood vessels22-2 Structures of Body DefensesThymic Epithelial Cells in the Cortex Surround lymphocytes in cortex Maintain blood–thymus barrierSecrete thymic hormones that stimulate:Stem cell divisionsT cell differentiation22-2 Structures of Body DefensesThymic Epithelial Cells in the Medulla Form concentric layers known as thymic (Hassall’s) corpusclesThe medulla has no blood–thymus barrierT cells can enter or leave bloodstreamThymus HormonesThymosin – an extract from the thymus that promotes development of lymphocytes22-2 Structures of Body DefensesThree Functions of the Spleen Removal of abnormal blood cells and other blood components by phagocytosisStorage of iron recycled from red blood cellsInitiation of immune responses by B cells and T cellsIn response to antigens in circulating blood22-2 Structures of Body DefensesAnatomy of the Spleen Attached to stomach by gastrosplenic ligamentContacts diaphragm and left kidneySplenic veins, arteries, and lymphatic vesselsCommunicate with spleen at hilum22-2 Structures of Body DefensesHistology of the Spleen Inside fibrous capsuleRed pulp contains many red blood cellsWhite pulp resembles lymphoid nodules22-2 Structures of Body DefensesTrabecular Arteries Branch and radiate toward capsuleFiner branches surrounded by white pulpCapillaries discharge red blood cells into red pulpRed PulpContains elements of circulating bloodPlus fixed and free macrophages22-2 Structures of Body DefensesSplenic Circulation Blood passes through:Network of reticular fibersThen enters large sinusoids (lined by macrophages)Which empty into trabecular veins22-2 Structures of Body DefensesSpleen Function Phagocytes and other lymphocytes in spleenIdentify and attack damaged and infected cellsIn circulating blood22-2 Structures of Body DefensesThe Lymphatic System and Body DefensesBody defenses provide resistance to fight infection, illness, and diseaseTwo categories of defenses Innate (nonspecific) immunity Adaptive (specific) immunity 22-2 Structures of Body DefensesInnate (Nonspecific) Immunity Always works the same way Against any type of invading agentNonspecific resistanceAdaptive (Specific) Immunity Protects against specific pathogensDepends on activities of lymphocytesSpecific resistance (immunity)Develops after exposure to environmental hazards22-3 Nonspecific DefensesSeven Major Categories of Innate (Nonspecific) Immunity Physical barriers Phagocytes Immune surveillance Interferons Complement Inflammatory response Fever22-3 Nonspecific DefensesPhysical BarriersKeep hazardous materials outside the bodyPhagocytes Attack and remove dangerous microorganismsImmune SurveillanceConstantly monitors normal tissuesWith natural killer cells (NK cells) 22-3 Nonspecific DefensesInterferons Chemical messengers that trigger production of antiviral proteins in normal cellsAntiviral proteinsDo not kill virusesBlock replication in cellComplement System of circulating proteins Assists antibodies in destruction of pathogens22-3 Nonspecific DefensesInflammatory ResponseLocalized, tissue-level response that tends to limit spread of injury or infection FeverA high body temperatureIncreases body metabolismAccelerates defensesInhibits some viruses and bacteria22-3 Nonspecific DefensesPhysical Barriers Outer layer of skinHairEpithelial layers of internal passagewaysSecretions that flush away materialsSweat glands, mucus, and urineSecretions that kill or inhibit microorganismsEnzymes, antibodies, and stomach acid22-3 Nonspecific DefensesTwo Classes of Phagocytes MicrophagesNeutrophils and eosinophilsLeave the bloodstreamEnter peripheral tissues to fight infections22-3 Nonspecific DefensesTwo Classes of Phagocytes MacrophagesLarge phagocytic cells derived from monocytes Distributed throughout bodyMake up monocyte–macrophage system (reticuloendothelial system)22-3 Nonspecific DefensesActivated Macrophages Respond to pathogens in several waysEngulf pathogen and destroy it with lysosomal enzymesBind to pathogen so other cells can destroy itDestroy pathogen by releasing toxic chemicals into interstitial fluid22-3 Nonspecific DefensesTwo Types of Macrophages Fixed macrophages Also called histiocytesStay in specific tissues or organsFor example, dermis and bone marrow Free macrophages Also called wandering macrophagesTravel throughout body22-3 Nonspecific DefensesSpecial Histiocytes Microglia found in central nervous systemKupffer cells found in liver sinusoidsFree MacrophagesSpecial free macrophagesAlveolar macrophages (phagocytic dust cells)22-3 Nonspecific DefensesMovement and PhagocytosisAll macrophages:Move through capillary walls (emigration)Are attracted or repelled by chemicals in surrounding fluids (chemotaxis)Phagocytosis begins:When phagocyte attaches to target (adhesion)And surrounds it with a vesicle22-3 Nonspecific DefensesImmunological Surveillance Is carried out by natural killer (NK) cellsActivated NK CellsIdentify and attach to abnormal cell (nonselective)Golgi apparatus in NK cell forms perforin vesiclesVesicles release proteins called perforins (exocytosis)Perforins lyse abnormal plasma membraneAlso attack cancer cells and cells infected with viruses22-3 Nonspecific DefensesImmunological Surveillance Cancer cells With tumor-specific antigens Are identified as abnormal by NK cellsSome cancer cells avoid NK cells (immunological escape)22-3 Nonspecific DefensesImmunological Surveillance Viral infections Cells infected with virusesPresent abnormal proteins on plasma membranesAllow NK cells to identify and destroy them22-3 Nonspecific DefensesInterferons Proteins (cytokines) released by activated lymphocytes and macrophagesCytokinesChemical messengers released by tissue cellsTo coordinate local activitiesTo act as hormones to affect whole body22-3 Nonspecific DefensesThree Types of Interferons Alpha-interferons Produced by leukocytesStimulate NK cells Beta-interferonsSecreted by fibroblastsSlow inflammation Gamma-interferonsSecreted by T cells and NK cellsStimulate macrophage activity22-3 Nonspecific DefensesComplementPlasma contains 30 special complement (C) proteinsThat form complement system and complement antibody actionComplement activationComplements work together in cascadesTwo pathways activate the complement system Classical pathway Alternative pathway22-3 Nonspecific DefensesComplement Activation: The Classical PathwayFast method C1 binds to: Antibody molecule attached to antigen (bacterium)Bound protein acts as enzymeCatalyzes chain reaction22-3 Nonspecific DefensesComplement Activation: The Alternative PathwaySlow method exposed to antigenFactor P (properdin)Factor BFactor D Interact in plasma 22-3 Nonspecific DefensesComplement Activation Both pathways end with:Conversion of inactive complement protein C3To active form C3b22-3 Nonspecific DefensesEffects of Complement ActivationPore formation Destruction of target plasma membranesFive complement proteins join to form membrane attack complex (MAC)Enhancement of phagocytosis by opsonization Complements working with antibodies (opsonins)Histamine releaseIncreases the degree of local inflammation and blood flow22-3 Nonspecific DefensesInflammation Also called inflammatory response A localized responseTriggered by any stimulus that kills cells or injures tissue22-3 Nonspecific DefensesCardinal Signs and Symptoms Swelling (tumor)Redness (rubor)Heat (calor)Pain (dolor) 22-3 Nonspecific DefensesThree Effects of InflammationTemporary repair and barrier against pathogensRetards spread of pathogens into surrounding areasMobilization of local and systemic defensesAnd facilitation of repairs (regeneration)22-3 Nonspecific DefensesProducts of Inflammation NecrosisLocal tissue destruction in area of injuryPusMixture of debris and necrotic tissueAbscessPus accumulated in an enclosed space 22-3 Nonspecific DefensesFever A maintained body temperature above 37.2C (99F)Pyrogens Any material that causes the hypothalamus to raise body temperatureCirculating pathogens, toxins, or antibody complexesEndogenous pyrogens or interleukin-1 (IL-1)Pyrogen released by active macrophagesA cytokine22-4 Specific DefensesAdaptive (Specific) Defenses Specific resistance (immunity)Responds to specific antigensWith coordinated action of T cells and B cells22-4 Specific DefensesSpecific Defenses T CellsProvide cell-mediated immunityDefend against abnormal cells and pathogens inside cellsB Cells Provide antibody-mediated immunityDefend against antigens and pathogens in body fluids22-4 Specific DefensesForms of Immunity Innate Present at birth AdaptiveAfter birth ActiveAntibodies develop after exposure to antigen PassiveAntibodies are transferred from another source22-4 Specific DefensesActive Immunity Naturally acquiredThrough environmental exposure to pathogensArtificially inducedThrough vaccines containing pathogens22-4 Specific DefensesPassive Immunity Naturally acquiredAntibodies acquired from the motherArtificially inducedBy an injection of antibodies22-4 Specific DefensesFour Properties of Immunity Specificity Each T or B cell responds only to a specific antigen and ignores all others VersatilityThe body produces many types of lymphocytesEach fights a different type of antigenActive lymphocyte clones itself to fight specific antigen22-4 Specific DefensesFour Properties of Immunity MemorySome active lymphocytes (memory cells):Stay in circulationProvide immunity against new exposure ToleranceImmune system ignores “normal” antigens (self-antigens) 22-4 Specific DefensesAn Introduction to the Immune ResponseTwo main divisionsCell-mediated immunity (T cells)Antibody-mediated immunity (B cells)22-5 T Cells and ImmunityFour Major Types of T Cells Cytotoxic T cells (also called TC cells)Attack cells infected by virusesResponsible for cell-mediated immunity Memory T cellsClone more of themselves in response to “remembered” antigen Helper T cells (also called TH cells)Stimulate function of T cells and B cells Suppressor T cells (also called TS cells)Inhibit function of T cells and B cells22-5 T Cells and ImmunityAntigen PresentationT cells only recognize antigens that are bound to glycoproteins in plasma membranes MHC Proteins The membrane glycoproteins that bind to antigensGenetically coded in chromosome 6The major histocompatibility complex (MHC)Differs among individuals 22-5 T Cells and ImmunityTwo Classes of MHC Proteins Class IFound in membranes of all nucleated cells Class II Found in membranes of antigen-presenting cells (APCs)Found in lymphocytes 22-5 T Cells and ImmunityClass I MHC Proteins Pick up small peptides in cell and carry them to the surfaceT cells ignore normal peptidesAbnormal peptides or viral proteins activate T cells to destroy cell22-5 T Cells and ImmunityClass II MHC Proteins Antigenic fragmentsFrom antigen processing of pathogens Bind to Class II proteins Inserted in plasma membrane to stimulate T cellsAntigen-presenting cells (APCs) Responsible for activating T cells against foreign cells and proteins22-5 T Cells and ImmunityPhagocytic APCs Free and fixed macrophagesIn connective tissuesKupffer cellsOf the liverMicrogliaIn the CNS22-5 T Cells and ImmunityNon-phagocytic APCs Langerhans cellsIn the skinDendritic cellsIn lymph nodes and spleen 22-5 T Cells and ImmunityAntigen Recognition Inactive T cell receptorsRecognize Class I or Class II MHC proteinsRecognize a specific antigenBinding occurs when MHC protein matches antigen22-5 T Cells and ImmunityCD Markers Also called cluster of differentiation markersIn T cell membranesMolecular mechanism of antigen recognitionMore than 70 typesDesignated by an identifying numberCD3 Receptor ComplexFound in all T cells22-5 T Cells and ImmunityTwo Important CD Markers CD8 Markers Found on cytotoxic T cells and suppressor T cellsRespond to antigens on Class I MHC proteins CD4 MarkersFound on helper T cellsRespond to antigens on Class II MHC proteinsCD8 or CD4 Markers Bind to CD3 receptor complexPrepare cell for activation22-5 T Cells and ImmunityCostimulation For T cell to be activated, it must be costimulatedBy binding to stimulating cell at second siteWhich confirms the first signal22-5 T Cells and ImmunityActivation of CD8 T Cells Activated by exposure to antigens on MHC proteinsOne responds quicklyProducing cytotoxic T cells and memory T cellsThe other responds slowlyProducing suppressor T cells22-5 T Cells and ImmunityCytotoxic T (TC) Cells Seek out and immediately destroy target cellsRelease perforinTo destroy antigenic plasma membrane Secrete poisonous lymphotoxinTo destroy target cellActivate genes in target cellThat cause cell to die22-5 T Cells and ImmunityMemory TC Cells Produced with cytotoxic T cellsStay in circulationImmediately form cytotoxic T cells if same antigen appears again22-5 T Cells and ImmunitySuppressor T Cells Secrete suppression factors Inhibit responses of T and B cellsAct after initial immune responseLimit immune reaction to single stimulus22-5 T Cells and ImmunityActivation of CD4 T cellsActive helper T cells (TH cells)Secrete cytokines Memory helper (TH) cellsRemain in reserve22-5 T Cells and ImmunityFour Functions of CytokinesStimulate T cell divisionsProduce memory TH cellsAccelerate cytotoxic T cell maturationAttract and stimulate macrophagesAttract and stimulate activity of cytotoxic T cellsPromote activation of B cells22-6 B Cells and ImmunityB Cells Responsible for antibody-mediated immunityAttack antigens by producing specific antibodiesMillions of populations, each with different antibody molecules22-6 B Cells and ImmunityB Cell Sensitization Corresponding antigens in interstitial fluids bind to B cell receptorsB cell prepares for activationPreparation process is sensitizationDuring sensitization, antigens are:Taken into the B cellProcessedReappear on surface, bound to Class II MHC protein22-6 B Cells and ImmunityHelper T Cells Sensitized B cell is prepared for activation but needs helper T cell activated by same antigenB Cell Activation Helper T cell binds to MHC complex Secretes cytokines that promote B cell activation and division22-6 B Cells and ImmunityB Cell Division Activated B cell divides into:Plasma cells Memory B cells22-6 B Cells and ImmunityPlasma Cells Synthesize and secrete antibodies into interstitial fluidMemory B Cells Like memory T cells, remain in reserve to respond to next infection22-6 B Cells and ImmunityAntibody Structure Two parallel pairs of polypeptide chains One pair of heavy chains One pair of light chainsEach chain contains:Constant segments Variable segments22-6 B Cells and ImmunityFive Heavy-Chain Constant Segments Determine five types of antibodiesIgGIgEIgDIgMIgA22-6 B Cells and ImmunityVariable Segments of Light and Heavy Chains Determine specificity of antibody moleculeBinding SitesFree tips of two variable segmentsForm antigen binding sites of antibody moleculeWhich bind to antigenic determinant sites of antigen molecule Antigen–Antibody ComplexAn antibody bound to an antigen22-6 B Cells and ImmunityThe Antigen–Antibody ComplexA Complete Antigen Has at least two antigenic determinant sitesBinds to both antigen-binding sites of variable segments of antibodyB Cell SensitizationExposure to a complete antigen leads to:B cell sensitizationImmune response22-6 B Cells and ImmunityHapten (Partial Antigens) Must attach to a carrier molecule to act as a complete antigenDangers of Haptens Antibodies produced will attack both hapten and carrier moleculeIf carrier is “normal”:Antibody attacks normal cellsFor example, penicillin allergy22-6 B Cells and ImmunityFive Classes of Antibodies Also called immunoglobulins (Igs)IgG, IgD, IgE, IgM, IgAAre found in body fluidsAre determined by constant segmentsHave no effect on antibody specificity22-6 B Cells and ImmunityFive Classes of AntibodiesIgG is the largest and most diverse class of antibodies80 percent of all antibodiesIgG antibodies are responsible for resistance against many viruses, bacteria, and bacterial toxins Can cross the placenta, and maternal IgG provides passive immunity to fetus during embryological developmentAnti-Rh antibodies produced by Rh-negative mothers are also IgG antibodies and produce hemolytic disease of the newborn22-6 B Cells and ImmunityFive Classes of AntibodiesIgE attaches as an individual molecule to the exposed surfaces of basophils and mast cellsWhen an antigen is bound by IgE molecules:The cell is stimulated to release histamine and other chemicals that accelerate inflammation in the immediate areaIgE is also important in the allergic response22-6 B Cells and ImmunityFive Classes of AntibodiesIgD is an individual molecule on the surfaces of B cells, where it can bind antigens in the extracellular fluidBinding can play a role in the sensitization of the B cell involved22-6 B Cells and ImmunityFive Classes of AntibodiesIgM is the first class of antibody secreted after an antigen is encounteredIgM concentration declines as IgG production acceleratesPlasma cells secrete individual IgM molecules, but it polymerizes and circulates as a five-antibody starburst The anti-A and anti-B antibodies responsible for the agglutination of incompatible blood types are IgM antibodiesIgM antibodies may also attack bacteria that are insensitive to IgG22-6 B Cells and ImmunityFive Classes of AntibodiesIgA is found primarily in glandular secretions such as mucus, tears, saliva, and semenAttack pathogens before they gain access to internal tissuesIgA antibodies circulate in blood as individual molecules or in pairsEpithelial cells absorb them from blood and attach a secretory piece, which confers solubility, before secreting IgA molecules onto the epithelial surface22-6 B Cells and ImmunitySeven Functions of Antigen–Antibody Complexes Neutralization of antigen binding sites Precipitation and agglutination – formation of immune complex Activation of complement Attraction of phagocytes Opsonization increasing phagocyte efficiency Stimulation of inflammation Prevention of bacterial and viral adhesion22-6 B Cells and ImmunityPrimary and Secondary Responses to Antigen Exposure Occur in both cell-mediated and antibody-mediated immunityFirst exposureProduces initial primary responseNext exposureTriggers secondary responseMore extensive and prolongedMemory cells already primed 22-6 B Cells and ImmunityThe Primary Response Takes time to developAntigens activate B cellsPlasma cells differentiateAntibody titer (level) slowly rises22-6 B Cells and ImmunityThe Primary Response Peak responseCan take two weeks to developDeclines rapidlyIgMIs produced faster than IgGIs less effective 22-6 B Cells and ImmunityThe Secondary Response Activates memory B cellsAt lower antigen concentrations than original B cellsSecrete antibodies in massive quantities22-6 B Cells and ImmunityEffects of Memory B Cell Activation IgGRises very high and very quicklyCan remain elevated for extended timeIgMProduction is also quickerSlightly extended 22-6 B Cells and ImmunityCombined Responses to Bacterial Infection Neutrophils and NK cells begin killing bacteriaCytokines draw phagocytes to areaAntigen presentation activates:Helper T cellsCytotoxic T cellsB cells activate and differentiatePlasma cells increase antibody levels22-6 B Cells and ImmunityCombined Responses to Viral Infection Similar to bacterial infectionBut cytotoxic T cells and NK cells are activated by contact with virus-infected cells22-7 Immune System DevelopmentImmune System Development Fetus can produce immune response (has immunocompetence)After exposure to antigenAt about three to four months22-7 Immune System DevelopmentDevelopment of Immunocompetence Fetal thymus cells migrate to tissues that form T cellsLiver and bone marrow produce B cellsFour-month fetus produces IgM antibodies22-7 Immune System DevelopmentBefore BirthMaternal IgG antibodiesPass through placentaProvide passive immunity to fetusAfter BirthMother’s milk provides IgA antibodiesWhile passive immunity is lost22-7 Immune System DevelopmentNormal Resistance Infant produces IgG antibodies through exposure to antigensAntibody, B cell, and T cell levels slowly rise to adult levelsAbout age 1222-7 Immune System DevelopmentCytokines of the Immune SystemChemical messengers involved in cellular immunityHormones and paracrine-like glycoproteinsExamples of cytokines:InterferonsInterleukinsTumor necrosis factors (TNFs)22-7 Immune System DevelopmentInterleukinsFunctions include:Increasing T cell sensitivity to antigens exposed on macrophage membranesStimulating B cell activity, plasma cell formation, and antibody production22-7 Immune System DevelopmentInterleukinsFunctions include:Enhancing nonspecific defensesStimulation of inflammationFormation of scar tissue by fibroblastsElevation of body temperature via the preoptic nucleus of the hypothalamusStimulation of mast cell formationPromotion of adrenocorticotropic hormone (ACTH) secretion by the anterior lobe of the pituitary glandModerating the immune responseSome interleukins help suppress immune function and shorten the immune response22-7 Immune System DevelopmentInterleukinsIL-1 and IL2, are important in stimulating and maintaining the immune responseWhen released by activated macrophages and lymphocytes, these cytokines stimulate the activities of other immune cells and of the secreting cell Result is a positive feedback loop that helps to recruit additional immune cells22-7 Immune System DevelopmentThree Types of Interferons Alpha-interferons Produced by leukocytesStimulate NK cells Beta-interferonsSecreted by fibroblastsSlow inflammation Gamma-interferonsSecreted by T cells and NK cellsStimulate macrophage activity22-7 Immune System DevelopmentTumor Necrosis Factors (TNFs)TNFs slow the growth of a tumor and kill sensitive tumor cellsActivated macrophages secrete one type of TNF and carry the molecules in their plasma membranesCytotoxic T cells produce a different type of TNF In addition to their effects on tumor cells:TNFs stimulate granular leukocyte production, promote eosinophil activity, cause fever, and increase T cell sensitivity to interleukins22-7 Immune System DevelopmentPhagocyte-Activating ChemicalsSeveral cytokines coordinate immune defenses by adjusting the activities of phagocytic cells Include factors that attract free macrophages and microphages and prevent their premature departure from the site of an injuryColony-Stimulating FactorsFactors are produced by active T cells, cells of the monocyte–macrophage system, endothelial cells, and fibroblastsCSFs stimulate the production of blood cells in red bone marrow and lymphocytes in lymphoid tissues and organs22-7 Immune System DevelopmentCytokines Are Often Classified According to Their Origins Lymphokines are produced by lymphocytes Monokines are secreted by active macrophages and other antigen-presenting cellsThese terms are misleading, because lymphocytes and macrophages may secrete the same cytokines Cells involved in adaptive immunity and tissue repair can also secrete cytokines22-7 Immune System DevelopmentImmune Disorders Autoimmune disordersImmunodeficiency diseaseAllergies22-7 Immune System DevelopmentAutoimmune Disorders A malfunction of system that recognizes and ignores “normal” antigensActivated B cells make autoantibodies against body cells Examples:ThyroiditisRheumatoid arthritisInsulin-dependent diabetes mellitus (IDDM)22-7 Immune System DevelopmentImmunodeficiency Diseases Result from:Problems with embryological development of lymphoid tissuesCan result in severe combined immunodeficiency disease (SCID)Viral infections such as HIVCan result in AIDSImmunosuppressive drugs or radiation treatmentsCan lead to complete immunological failure22-7 Immune System DevelopmentAllergies Inappropriate or excessive immune responses to antigensAllergensAntigens that trigger allergic reactions22-7 Immune System DevelopmentFour Categories of Allergic Reactions Immediate hypersensitivity (Type I) Cytotoxic reactions (Type II) Immune complex disorders (Type III) Delayed hypersensitivity (Type IV)22-7 Immune System DevelopmentType I Allergy Also called immediate hypersensitivityA rapid and severe response to the presence of an antigenMost commonly recognized type of allergyIncludes allergic rhinitis (environmental allergies)22-7 Immune System DevelopmentType I Allergy Sensitization leads to:Production of large quantities of IgE antibodies distributed throughout the body Second exposure leads to:Massive inflammation of affected tissues22-7 Immune System DevelopmentType I AllergySeverity of reaction depends on:Individual sensitivityLocations involvedAllergens (antigens that trigger reaction) in bloodstream may cause anaphylaxis22-7 Immune System DevelopmentAnaphylaxis Can be fatalAffects cells throughout bodyChanges capillary permeabilityProduces swelling (hives) on skinSmooth muscles of respiratory system contractMake breathing difficultPeripheral vasodilationCan cause circulatory collapse (anaphylactic shock)22-7 Immune System DevelopmentAntihistamines Drugs that block histamine released by mast cells Can relieve mild symptoms of immediate hypersensitivity Benadryl22-7 Immune System DevelopmentStress and the Immune Response GlucocorticoidsSecreted to limit immune response Long-term secretion (chronic stress)Inhibits immune responseLowers resistance to disease22-7 Immune System DevelopmentFunctions of Glucocorticoids Depression of the inflammatory response Reduction in abundance and activity of phagocytesInhibition of interleukin secretion22-8 Effects of Aging on the Immune SystemImmune System Diminishes with AgeIncreasing vulnerability to infections and cancerFour Effects of AgingThymic hormone production is greatly reducedT cells become less responsive to antigensFewer T cells reduces responsiveness of B cellsImmune surveillance against tumor cells declines22-9 Immune System Integration Nervous and Endocrine Systems Interact with thymic hormonesAdjust sensitivity of immune response ................
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