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Ch 6 Adaptive Immune

Apr 06, 2018

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    Chapter 6

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    The Adaptive ImmuneThe Adaptive ImmuneResponseResponse

    In adaptive immunity, nonspecific

    phagocytes present antigen to specific Tcells, triggering the production of effector

    T cells and antibodies. Immune T cells

    and antibodies react directly or indirectlyto neutralize or destroy the antigen.

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    The adaptive immune response is characterized byspecificityfor the antigen,

    the ability to respond more vigorously when reexposed to thesame antigen (memory),

    the ability to discriminate self antigens from nonself antigens(tolerance).

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    Acquired/Adaptive/Specific ImmunityFeatures

    Specificity

    Memory

    Specialization

    Self/Nonself recognition

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    Innate vs. adaptive immunityInnate vs. adaptive immunity Innate immunity

    First line of defense (present in all individuals at alltimes)

    Immediate (0 4 hours)

    Non-specific

    Does not generate lasting protective immunity

    Adaptive (acquired) immune response(late: > 96 hours)

    Is initiated if innate immune response is not adequate (>4 days)

    Antigen-specific immunity

    Generates lasting protective immunity (e.g. Antibodies,memory T-cells)

    Humoral and cell-mediated

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    Immune system cellsImmune system cells

    Innate immunityGranulocytes(i.e.neutrophils)

    Macrophages

    Dendritic cells

    Natural killer (NK) cells

    Adaptive immunity

    LymphocyteB cells

    T cells Cytotoxic T cells (CTLs)

    Helper T cells (Th)

    Memory cells

    www.gcarlson.com/cellular_active_neutrophils.htmhttp://

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    Cells of the adaptive immune

    systemDendritic cells (most importantAPC cell)

    B-cells

    Humoral immune responseProduce antibodies

    APC cells

    T- cells

    Cell-mediated immune responseCytotoxic T cells (CD8)

    Helper T cells (CD4)

    Memory cellshttp://www.biology.arizona.edu/immunology/tutorials/immunology/graphics/T_helper_act.gif

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    Induction of the adaptiveInduction of the adaptive

    immune responseimmune response

    Pathogen ingested byPathogen ingested by

    immature dendritic cellimmature dendritic cell

    Migrate to the lymphMigrate to the lymph

    nodesnodes

    Interact with nave TInteract with nave T

    lymphocyteslymphocytes

    Activates

    TH1

    MHC II

    Macrophage

    Dead intracellular bacteria

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    Lymphocytes (effector cells ofLymphocytes (effector cells of

    the adaptive immune system)the adaptive immune system)

    Lymphocytes (effector cells ofLymphocytes (effector cells of

    the adaptive immune system)the adaptive immune system) Antigen receptors with single specificity (T and B cells)

    GeneGene rere--arrangementarrangement

    Clonal selection

    InteractionInteraction ofof antigenantigen andand lymphocytelymphocyte receptorreceptor ActivationActivation ofof lymphocytelymphocyte

    DifferentiationDifferentiation (progeny(progeny withwith identicalidentical specificity)specificity)

    T and B cells have 2 distinct recognition systems for detectingpathogens

    TT cellscells -- recognizerecognize intracellularintracellular pathogenspathogens (T(T cellcell receptors,receptors,TCR)TCR)

    BB cellscells recognizerecognize extracellularextracellular pathogenspathogens(Immunoglobins,(Immunoglobins, BCRBCR

    Antigen receptors with single specificity (T and B cells)

    GeneGene rere--arrangementarrangement

    Clonal selection

    InteractionInteraction ofof antigenantigen andand lymphocytelymphocyte receptorreceptor ActivationActivation ofof lymphocytelymphocyte

    DifferentiationDifferentiation (progeny(progeny withwith identicalidentical specificity)specificity)

    T and B cells have 2 distinct recognition systems for detectingpathogens

    TT cellscells -- recognizerecognize intracellularintracellular pathogenspathogens (T(T cellcell receptors,receptors,TCR)TCR)

    BB cellscells recognizerecognize extracellularextracellular pathogenspathogens(Immunoglobins,(Immunoglobins, BCRBCR

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    A single progenitor cellgives rise to a large

    number of lymphocytes,each with a different

    specificity

    Clonal selection

    Pool of navelymphocytes

    Selfantigen

    Selfantigen

    Removal of potentially

    self-reactive immaturelymphocytes by clonal

    deletion

    Foreign antigenProliferation anddifferentiation ofactivated specific

    lymphocytes to forma clone of effector

    cellsEffector cellseliminate antigen

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    Membrane-bound form of the

    antibody

    V-region (variable) Antigen-binding specificity

    Fc-region (constant)

    Determines how the

    antibody disposes of thebound pathogen

    Fc region

    V region; At binding

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    Single antigenrecognition site

    Always a cell surfacemolecule

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    Effector cellsActive-duty cells

    Die off during or just

    afterbattle

    Memory cellsReserve cellsCalled up to the

    front for later battles

    Antigen

    T cellor

    B cell

    Active duty?

    Reserves?

    cloneclonefamily of cellsfamily of cells

    descended from onedescended from one

    ancestor cellancestor cell

    cloneclonefamily of cellsfamily of cells

    descended from onedescended from one

    ancestor cellancestor cellNaveActiveChemicalsignal

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    Humoral immune responseHumoral immune response

    Cell-surface immunoglobulin receptors

    (BCR) detect extracellular pathogens

    Once activated, secrete immunoglobulins as

    soluble antibodies

    Antibodies

    Variable region (2 identical antigen-binding

    sites) Constant region (determines how antibody

    disposes of the pathogen once it is bound)

    Cell-surface immunoglobulin receptors

    (BCR) detect extracellular pathogens

    Once activated, secrete immunoglobulins as

    soluble antibodies

    Antibodies

    Variable region (2 identical antigen-binding

    sites) Constant region (determines how antibody

    disposes of the pathogen once it is bound)

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    Generation of Antibody Diversity: Production

    of Unique Fab Sites through Gene

    Translocation

    the immune system of the body has no idea as to whatantigens it may eventually encounter.

    Therefore, it has evolved a system that possesses thecapability of responding to any conceivable antigen.

    The immune system can do this because both B-

    lymphocytes and T-lymphocytes have evolved aunique system of gene-splicing called genetranslocation , a type ofgene-shuffling process wherevarious different genes along a chromosome are cutout of one location and joined with other genes

    along the chromosome.

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    Clonal Selection and Clonal

    Expansion

    Clonal Selection and Clonal

    Expansion

    During its development, each B-lymphocytebecomes genetically programmed, through aprocess called gene translocation, to make aunique antibody molecule that will functionas a B-cell receptor.

    Molecules of that antibody are then placedon the cell's surface where it can react withepitopes of an antigen.

    Cytokines from an activated T4-lymphocytenow enable the activated B-lymphocyte toproliferate into a large clone of identical B-lymphocytes.

    The B-lymphocytes now differentiate intoantibody-secreting B-lymphocytes andplasma cells that secrete large quantities ofantibodies "fitting" the original epitope.Some B-lymphocytes differentiate into B-memory cells capable of anamnesticresponse .

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    Antibody interactions

    Antibodies can participate in host defenses in 3 mainways:

    Neutralization

    Ab bind and neutralize bacterial toxins, bacteria andvirus particles preventing interaction with host cells

    Ingestion by macrophages

    Opsonization Allows recognition by phagocytes or NK cells (antibody-

    dependent cell mediated cytotoxicity, ADCC)

    Ingestion or killing

    Complement activation Activation of complement system

    Ingestion by phagocytes

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    Antigen recognition by T-cells

    T cells detect presence of intracellular

    pathogens

    T cells receptors

    Peptide fragments

    Major histocompatibility complex (MHC)

    MHC I (cytotoxic T cells /CD+8)

    MHC II (T helper (1 and 2)/ CD+4)

    Cell death

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    Antigen recognition by T-cells

    Cytotoxic T cells (CD8)recognize antigen

    presented by MHC I

    and kills thecell

    Kills

    CytotoxicT cell

    MHC I

    TH1 cells (CD4)recognize antigen

    presented by MHC II

    and activatesmacrophages

    TH2 cells (CD4)recognize antigen

    presented by MHC II

    and activates B cells

    Activates

    TH1

    MHCII

    Macrophage

    Virus-infected cell

    Apoptoticcell

    Dead intracellularbacteria

    Activates

    TH2

    MHCII

    B cell

    Anti-toxin antibodies