Adaptive Immunity Chapter 7 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate...

Adaptive ImmunityAdaptive Immunity

Chapter 7Chapter 7

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.

2Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.

Adaptive ImmunityAdaptive Immunity Works together with innate immunity, aka Works together with innate immunity, aka

inflammationinflammation SpecificitySpecificity

Each T or B cell recognizes only one antigen, but Each T or B cell recognizes only one antigen, but together a group of T and B cells recognize a host of together a group of T and B cells recognize a host of foreign antigensforeign antigens

MemoryMemory Confers long-term protectionConfers long-term protection


End Products End Products of Adaptive Immunityof Adaptive Immunity

Lymphocytes (cellular immunity): T and B cellsLymphocytes (cellular immunity): T and B cells Antibody (humoral immunity): immune Antibody (humoral immunity): immune

globulinsglobulins


Adaptive ImmunityAdaptive Immunity Clonal diversityClonal diversity

Production of T and B lymphocytesProduction of T and B lymphocytes Antigen recognitionAntigen recognition Lymphocyte specificityLymphocyte specificity

Clonal selectionClonal selection Antigen processed and presented to immune cells Antigen processed and presented to immune cells

by APCsby APCs Cellular interaction of T cells and APCsCellular interaction of T cells and APCs


Clonal DiversityClonal Diversity

Primary (central) and Primary (central) and secondary secondary (peripheral)(peripheral)lymphoid tissueslymphoid tissues


Clonal Diversity and SelectionClonal Diversity and Selection


Types of ImmunityTypes of Immunity Natural immunityNatural immunity

Active immunityActive immunity

Passive immunityPassive immunity


Humoral and Humoral and Cell-Mediated ImmunityCell-Mediated Immunity

The cellular and humoral responses are not The cellular and humoral responses are not independentindependent

Humoral immunityHumoral immunity ““Fluid” immunityFluid” immunity Circulating antibodyCirculating antibody

Cell-mediated immunityCell-mediated immunity T cell differentiationT cell differentiation


Active vs. Passive ImmunityActive vs. Passive Immunity Active immunityActive immunity

Antibodies or T cells produced after either a Antibodies or T cells produced after either a natural exposure to an antigen or after natural exposure to an antigen or after immunizationimmunization

Passive immunityPassive immunity Preformed antibodies or T lymphocytes are Preformed antibodies or T lymphocytes are

transferred from a donor to a recipienttransferred from a donor to a recipient


Recognition and ResponseRecognition and Response Required for a successful immune responseRequired for a successful immune response Clusters of differentiation (CD)Clusters of differentiation (CD)

Originally used to describe proteins found on the Originally used to describe proteins found on the surface of lymphocytessurface of lymphocytes

Now it is a labeling system used to identify a Now it is a labeling system used to identify a family of proteins on many cellsfamily of proteins on many cells


AntigenAntigen A molecule that can react with (or be recognized A molecule that can react with (or be recognized

by) the immune systemby) the immune system Recognized as nonselfRecognized as nonself

Pathogens (viruses, bacteria, fungi, etc.)Pathogens (viruses, bacteria, fungi, etc.) Bee venomBee venom PollenPollen FoodsFoods TissueTissue Blood productsBlood products


Recognition and ResponseRecognition and Response Antigens vs. immunogensAntigens vs. immunogens

Antigen (Ag): a molecule that binds and reacts Antigen (Ag): a molecule that binds and reacts with antibody (Ab) or lymphocyte receptorswith antibody (Ab) or lymphocyte receptors

Immunogen: an Ag that can trigger an immune Immunogen: an Ag that can trigger an immune responseresponse


Self-Antigen and ToleranceSelf-Antigen and Tolerance

Degree of foreignness to host Degree of foreignness to host Most importantMost important

SizeSize Small molecular weight Ag’s called haptens; can’t Small molecular weight Ag’s called haptens; can’t

trigger immune response themselves but can trigger immune response themselves but can when bound to a carrier protein when bound to a carrier protein

Chemical complexity Chemical complexity AmountAmount


Self-Antigen and ToleranceSelf-Antigen and Tolerance

Tolerance: we recognize ourselves as Tolerance: we recognize ourselves as not not foreign foreign Central tolerance: lymphocytes with receptors Central tolerance: lymphocytes with receptors

against self-antigens are eliminated against self-antigens are eliminated Peripheral tolerance: prevents recognition by Peripheral tolerance: prevents recognition by

lymphocytes and Ab’s lymphocytes and Ab’s


Antigen PresentationAntigen Presentation

Antigen-presenting cells (APCs)Antigen-presenting cells (APCs) Major histocompatibility complex (MHC)Major histocompatibility complex (MHC)

Glycoproteins on the surface of all human cells Glycoproteins on the surface of all human cells (except RBCs)(except RBCs)

Also called human leukocyte antigens (HLAs)Also called human leukocyte antigens (HLAs) MHC class I moleculesMHC class I molecules

• A, B, and CA, B, and C

MHC class II moleculesMHC class II molecules• DR, DP, and DQDR, DP, and DQ

MHC class III moleculesMHC class III molecules


Molecules That Present AntigenMolecules That Present Antigen

Ag is processed within cellsAg is processed within cells Expressed on the cell surface in a specific Expressed on the cell surface in a specific

mannermanner Some Ag’s need special APCs; others can be Some Ag’s need special APCs; others can be

processed by most any cell typeprocessed by most any cell type


Molecules That Present AntigenMolecules That Present Antigen

MHCMHC


TransplantationTransplantation Cells in transplanted tissue from one Cells in transplanted tissue from one

individual have a different set of MHC surface individual have a different set of MHC surface antigens than those of recipient antigens than those of recipient

Thus recipient can mount an immune Thus recipient can mount an immune response against foreign MHC molecules response against foreign MHC molecules

HaplotypeHaplotype Combination of A, B, C, DR, DQ, and DP alleles Combination of A, B, C, DR, DQ, and DP alleles


Tissue/Organ TransplantationTissue/Organ Transplantation

Inheritance of human leukocyte antigens Inheritance of human leukocyte antigens (HLAs) (synonym for MHC molecules)(HLAs) (synonym for MHC molecules)


CD1CD1 Antigen-presenting moleculesAntigen-presenting molecules Found on antigen-presenting and thymus Found on antigen-presenting and thymus

cellscells Present lipid antigensPresent lipid antigens

Mycobacterium, tuberculosisMycobacterium, tuberculosis


Antigen RecognitionAntigen Recognition Antigen is directly recognized by circulating Antigen is directly recognized by circulating

antibody, antigen receptors on B cells (BCR), antibody, antigen receptors on B cells (BCR), and T lymphocytes (TCR) and T lymphocytes (TCR)


AntibodiesAntibodies Also called immunoglobulinsAlso called immunoglobulins Produced by plasma cells Produced by plasma cells Classes of antibodyClasses of antibody

IgG, IgA, IgM, IgE, and IgDIgG, IgA, IgM, IgE, and IgD• Characterized by antigenic, structural, and functional Characterized by antigenic, structural, and functional

differencesdifferences


Molecules That Recognize AntigenMolecules That Recognize Antigen

Antibodies: classes of immunoglobulinsAntibodies: classes of immunoglobulins


Molecules That Recognize AntigenMolecules That Recognize Antigen B-cell receptor complex: antibodies and B-cell receptor complex: antibodies and

accessory moleculesaccessory molecules


AntibodiesAntibodies

ProteinProtein Part of the adaptive immune response that Part of the adaptive immune response that

interacts with antigeninteracts with antigen Usually classes of immunoglobulinsUsually classes of immunoglobulins


Antibody StructureAntibody Structure Antigen-binding fragment (Fab)Antigen-binding fragment (Fab)

Recognition sites (receptors) for antigenic Recognition sites (receptors) for antigenic determinantsdeterminants

Crystalline fragment (Fc)Crystalline fragment (Fc) Responsible for biologic functionResponsible for biologic function

Polypeptide chains (4)Polypeptide chains (4) Light chains (2) and heavy chains (2)Light chains (2) and heavy chains (2)


Antigen BindingAntigen Binding

Amino acid sequences of the variable regions Amino acid sequences of the variable regions of the heavy and light chainsof the heavy and light chains

Framework regions control antibody foldingFramework regions control antibody folding Lock and keyLock and key

Noncovalent chemical interactionsNoncovalent chemical interactions Antibody valenceAntibody valence

IgG, IgD, and IgE—2IgG, IgD, and IgE—2 IgA—4IgA—4 IgM—theoretically 10, likely 5IgM—theoretically 10, likely 5


AntibodiesAntibodies ClassesClasses IgMIgM IgGIgG IgAIgA IgEIgE IgDIgD


Antibodies: Products of Antibodies: Products of Adaptive ImmunityAdaptive Immunity


AntibodiesAntibodies Classes—IgMClasses—IgM


Immunoglobulin M (IgM)Immunoglobulin M (IgM) Largest of the immunoglobulinsLargest of the immunoglobulins Pentamer stabilized by a J-chainPentamer stabilized by a J-chain First antibody produced during the primary First antibody produced during the primary

response to an antigenresponse to an antigen Synthesized during fetal lifeSynthesized during fetal life


AntibodiesAntibodies Classes—IgGClasses—IgG


Immunoglobulin G (IgG)Immunoglobulin G (IgG) Most abundant class (80%-85%)Most abundant class (80%-85%) Transported across the placentaTransported across the placenta Four classes Four classes

IgG1, IgG2, IgG3, and IgG4IgG1, IgG2, IgG3, and IgG4


AntibodiesAntibodies Classes—IgAClasses—IgA


Secretory (Mucosal) Secretory (Mucosal) Immune SystemImmune System

Lymphoid tissues that protect the external Lymphoid tissues that protect the external surfaces of the bodysurfaces of the body

Antibodies present in tears, sweat, saliva, Antibodies present in tears, sweat, saliva, mucus, and breast milkmucus, and breast milk

IgA is the dominant immunoglobulinIgA is the dominant immunoglobulin Small numbers of IgG and IgM are presentSmall numbers of IgG and IgM are present


Immunoglobulin A (IgA)Immunoglobulin A (IgA) Two classes Two classes

IgA1 molecules: predominantly in the bloodIgA1 molecules: predominantly in the blood IgA2 molecules: predominantly in normal body IgA2 molecules: predominantly in normal body

secretionssecretions IgAs in body secretions are dimers anchored IgAs in body secretions are dimers anchored

by J-chain and “secretory” pieceby J-chain and “secretory” piece Secretory piece may function to protect IgAs Secretory piece may function to protect IgAs

against enzyme degradationagainst enzyme degradation


AntibodiesAntibodies Classes—IgEClasses—IgE


Immunoglobulin E (IgE)Immunoglobulin E (IgE) Least concentrated of the immunoglobulin Least concentrated of the immunoglobulin

classes in the circulationclasses in the circulation Mediator of many common allergic responsesMediator of many common allergic responses

Fc portions of IgEs are bound to mast cellsFc portions of IgEs are bound to mast cells Defender against parasitesDefender against parasites


IgEIgE


AntibodiesAntibodies Classes—IgDClasses—IgD


Immunoglobulin D (IgD)Immunoglobulin D (IgD) Limited information on IgD functionLimited information on IgD function Low concentration in the bloodLow concentration in the blood Located primarily on the surface of Located primarily on the surface of

developing B lymphocytesdeveloping B lymphocytes Function as one type of B cell antigen Function as one type of B cell antigen

receptorreceptor


T-Cell–Receptor ComplexT-Cell–Receptor Complex Antibody-like transmembrane protein (TCR)Antibody-like transmembrane protein (TCR) Accessory proteins for intracellular signaling Accessory proteins for intracellular signaling

Referred to as CD3Referred to as CD3 T-cell–receptor complex: transmembrane T-cell–receptor complex: transmembrane

proteins and accessory proteinsproteins and accessory proteins


B-Cell–Receptor ComplexB-Cell–Receptor Complex Located on surface of B cellsLocated on surface of B cells Consists of:Consists of:

Antigen-recognition molecules Antigen-recognition molecules • Monomer IgM and IgD Monomer IgM and IgD

Accessory intracellular-signaling moleculesAccessory intracellular-signaling molecules• Ig-alpha and Ig-beta heterodimersIg-alpha and Ig-beta heterodimers


Generation of Clonal DiversityGeneration of Clonal Diversity All necessary receptor specificities are All necessary receptor specificities are

producedproduced Takes place in the primary (central) lymphoid Takes place in the primary (central) lymphoid

organsorgans Results in immature but immunocompetent T Results in immature but immunocompetent T

and B cellsand B cells Primarily occurs in the fetusPrimarily occurs in the fetus


Clonal SelectionClonal Selection Immunocompetent T and B cells migrate from Immunocompetent T and B cells migrate from

the primary to the secondary lymphoid organs the primary to the secondary lymphoid organs to await antigento await antigen

Primarily after birthPrimarily after birth Clonal selection is initiated by antigenClonal selection is initiated by antigen Final productsFinal products

Plasma cells that produce antibody, effector cells Plasma cells that produce antibody, effector cells that help Th, Tc, or Treg, and memory B and T that help Th, Tc, or Treg, and memory B and T cellscells


T-Cell MaturationT-Cell Maturation The thymus is the central lymphoid organ of T The thymus is the central lymphoid organ of T

cell developmentcell development T cells move from thymic cortex to the T cells move from thymic cortex to the

medullamedulla ChangesChanges

Development of the T cell receptors and Development of the T cell receptors and expression of surface moleculesexpression of surface molecules

T cells are released into the blood and take T cells are released into the blood and take up residence in the secondary lymph organsup residence in the secondary lymph organs


The Immune Response ProcessThe Immune Response Process Antigen processingAntigen processing Clonal selectionClonal selection Mounting a defense against the foreign Mounting a defense against the foreign

antigenantigen Production of memory cellsProduction of memory cells


Antigen Processing and Antigen Processing and PresentationPresentation

Antigens require processing and presentation Antigens require processing and presentation by APCsby APCs Dendritic cells, macrophages, B lymphocytesDendritic cells, macrophages, B lymphocytes

For this to occur, antigen must be the For this to occur, antigen must be the appropriate type, the lymphocytes must appropriate type, the lymphocytes must recognize the presented antigen, and the recognize the presented antigen, and the antigen must be presented appropriately antigen must be presented appropriately


Helper T LymphocytesHelper T Lymphocytes ““Help” the antigen-driven maturation of B and Help” the antigen-driven maturation of B and

T cellsT cells Facilitate and magnify the interaction Facilitate and magnify the interaction

between APCs and immunocompetent between APCs and immunocompetent lymphocyteslymphocytes

StepsSteps Th interacts through antigen-specific and antigen-Th interacts through antigen-specific and antigen-

independent mechanismsindependent mechanisms Undergoes differentiationUndergoes differentiation Mature Th interacts with plasma or T-effector cellsMature Th interacts with plasma or T-effector cells


Helper T LymphocytesHelper T Lymphocytes SubsetsSubsets

Th1 cells provide help in developing cell-mediated Th1 cells provide help in developing cell-mediated immunityimmunity

Th2 cells provide help in developing humoral Th2 cells provide help in developing humoral immunityimmunity

Differences based on cytokine productionDifferences based on cytokine production


B-Cell ActivationB-Cell Activation

When an immunocompetent B cell encounters an When an immunocompetent B cell encounters an antigen for the first time, B cells with specific antigen for the first time, B cells with specific BCRs are stimulated to differentiate and BCRs are stimulated to differentiate and proliferate proliferate

Differentiated B cell becomes a plasma cellDifferentiated B cell becomes a plasma cell A plasma cell is a factory for antibody productionA plasma cell is a factory for antibody production

Single class or subclass of antibodySingle class or subclass of antibody


B-Cell ActivationB-Cell Activation Antibody class switchAntibody class switch

Major component of B cell maturationMajor component of B cell maturation During clonal selection B cell can change class of During clonal selection B cell can change class of

Ab (IgG, IgA, IgE)Ab (IgG, IgA, IgE) DNA cut then mendedDNA cut then mended Specificity maintainedSpecificity maintained


B-Cell ActivationB-Cell Activation Primary vs. secondary immune responsePrimary vs. secondary immune response


Primary and Secondary Primary and Secondary ResponsesResponses

Primary responsePrimary response Initial exposureInitial exposure Latent period or lag phaseLatent period or lag phase

• B-cell differentiation is occurringB-cell differentiation is occurring

After 5 to 7 days, an IgM antibody for a specific After 5 to 7 days, an IgM antibody for a specific antigen is detectedantigen is detected

An IgG response equal or slightly less follows the An IgG response equal or slightly less follows the IgM responseIgM response


Primary and Secondary Primary and Secondary ResponsesResponses

Secondary responseSecondary response More rapidMore rapid Larger amounts of antibody are producedLarger amounts of antibody are produced Rapidity is due to the presence of memory cells Rapidity is due to the presence of memory cells

that do not have to differentiatethat do not have to differentiate IgM is produced in similar quantities to the primary IgM is produced in similar quantities to the primary

response, but IgG is produced in considerably response, but IgG is produced in considerably greater numbersgreater numbers


Class SwitchClass Switch Immunocompetent B cells use IgM and IgD Immunocompetent B cells use IgM and IgD

as receptorsas receptors During clonal selection, B cells have the During clonal selection, B cells have the

option of changing the class of the antibodyoption of changing the class of the antibody One of four IgGs, one of two IgAs, IgE, or an IgM One of four IgGs, one of two IgAs, IgE, or an IgM

in a pentamer formin a pentamer form DNA rearrangement DNA rearrangement


B Cell Clonal SelectionB Cell Clonal Selection


T Cell ActivationT Cell Activation Binding antigen to T cell receptorsBinding antigen to T cell receptors Allows:Allows:

Direct killing of foreign or abnormal cellsDirect killing of foreign or abnormal cells Assistance or activation of other cellsAssistance or activation of other cells

T regulatory cells (Treg)T regulatory cells (Treg) Regulate the immune response to avoid attacking Regulate the immune response to avoid attacking

“self”“self” Memory T cellsMemory T cells


T Cell ActivationT Cell Activation


T Cell ActivationT Cell Activation T regulatory cells (Tregs)T regulatory cells (Tregs)

(previously called T suppressor cells)(previously called T suppressor cells) To avoid overactivation of immune systemTo avoid overactivation of immune system To avoid attacking self-antigensTo avoid attacking self-antigens Subject of much researchSubject of much research


Antibody FunctionAntibody Function DirectDirect

NeutralizationNeutralization AgglutinationAgglutination PrecipitationPrecipitation

IndirectIndirect OpsonizationOpsonization

Degree of antibody protection is assessed by Degree of antibody protection is assessed by an antibody titeran antibody titer


Antibody FunctionAntibody Function Neutralizing bacteriaNeutralizing bacteria


Antibody FunctionAntibody Function Neutralizing virusesNeutralizing viruses


Antibody FunctionAntibody Function

Forming antigen-antibody complexesForming antigen-antibody complexes


Antibody FunctionAntibody Function OpsonizationOpsonization


Cell-Killing MechanismsCell-Killing Mechanisms

Cytotoxic T lymphocytesCytotoxic T lymphocytes Destroy cancer cells or cells infected with virusDestroy cancer cells or cells infected with virus Perforin, granzymes, or direct receptor Perforin, granzymes, or direct receptor

interactionsinteractions


Other CellsOther Cells Natural killer (NK) cells Natural killer (NK) cells

Complement Tc cell mechanismsComplement Tc cell mechanisms TregsTregs

Provide peripheral toleranceProvide peripheral tolerance Affect recognition of antigen and suppress Affect recognition of antigen and suppress

proliferative steps of antigen recognition proliferative steps of antigen recognition


Cell-Killing Mechanisms Cell-Killing Mechanisms


Fetal and Neonatal ImmunityFetal and Neonatal Immunity Antibody function is deficientAntibody function is deficient

Capable of primary IgM response; unable to Capable of primary IgM response; unable to produce an IgG challengeproduce an IgG challenge

Immunity provided by maternal antibodyImmunity provided by maternal antibody Trophoblastic cells transport maternal IgG across Trophoblastic cells transport maternal IgG across

the placentathe placenta Newborn IgG levels are near adult levelsNewborn IgG levels are near adult levels


Fetal and Neonatal ImmunityFetal and Neonatal Immunity


Aging and Immune FunctionAging and Immune Function Decreased T cell activityDecreased T cell activity

Thymic size is 15% of its maximum sizeThymic size is 15% of its maximum size Decreased production of specific antibodiesDecreased production of specific antibodies Increase in circulating antigen-antibody Increase in circulating antigen-antibody

complexescomplexes Increase in circulating autoantibodiesIncrease in circulating autoantibodies Decrease in circulating memory B cellsDecrease in circulating memory B cells

Adaptive Immunity Chapter 7 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate...

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