Cell Mediated Acquired Immunity

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    Cell-Mediated immuneresponse

    Recognition and the binding of a maturelymphocyte to an antigen induces thelymphocyte to divide rapidly.

    This proliferation of lymphocytes is calledclonal selection. Two types of clones areproduced: short-lived activated effector cellsand long-lived memory cells

    These effector cells activate B cells orMacrophages, or destroys infected, tumor, ortransplanted cells directly or through release of

    soluble mediators i.e. cytokines and Controls

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    Why it is known as cellmediated

    It is based on type of microbial invaders those are facedby immune system.

    Microbial invaders fall into two broad categories-In one category-organisms that originate outside the

    body including most bacteria, fungi as well as manyprotoza and invading helminths.The second category consists of the organisms that

    originate or live inside the bodys own cells includingviruses and intracellular bacteria or protozoa.

    Cell mediated immune system is directed againstintracellular or endogenous invaders that invade cells.

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    How the antigen ispresented to lymphocytes

    All nucleated cells of body trap endogenos antigenswith the help of MHC 1 receptors on their surface and

    then present to cytotoxic T- lymphocytes also having

    receptors for trapping.

    Its the main way of cell mediated immunity.

    Professional antigen presenting cells also help in

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    Types of antigenpresenting cells (APC)

    1. Dendritic cellsPhagocytic dendritic cells (DC) of tissues

    (Most potent stimulators of T cell responses)

    Germinal Center Dendritic Cells (GCDCs)Thymic Interdigitating Dendritic Cells (IDCs)

    Interstitial Dendritic Cells

    2. B cells as APCPresent Ag to T cells (TH2)

    3. Macrophages

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    The Role of the MHCIn infected cells, MHC molecules bind and transport

    antigen fragments to the cell surface, a process

    called antigen presentation.

    T cell can then detect the antigen fragmentdisplayed on the cells surface.

    Depending on their source, peptide antigens are

    handled by different classes of MHC molecules,

    mainly 2 are involved in the cell mediated immunity

    which are as follows-

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    The Two Classes Of MHCMolecules

    MHC Class I

    Class I MHC molecules are found on almost all

    nucleated cells of the body and Presents Agderived from intracellular source/cytosol.

    They display peptide antigens to cytotoxic T

    cells

    cytotoxic T cells kill target

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    MHC Class II

    Class II MHC molecules are located mainly on

    dendritic cells, macrophages, and B cells and

    Present Ag derived from extracellular or cell-bound

    source.

    These antigen-presenting cells then displayantigens to inflammatory T cells and helper T cells.

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    T Cells

    Originate in stem cells in bone marrow

    Change to T cells in thymus

    Become sensitized to specific antigenProduce cell-mediated immunity following T cell

    activation (in peripheral lymphoid organ) -

    Cytotoxic T cells (Tcyt) Kill infected targetcells Inflammatory (TH1) and Helper (TH2) T

    cells Activation of other cells (macrophages

    and B cells, respectively)

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    Way of functioning of T-cells

    Inflammatory T cells = TH1

    Activate macrophages

    MHC class II-restricted

    Helper T cells (TH2)

    Help to eradicate extracellular pathogens

    Activated helper T cells secrete cytokines that

    stimulate other lymphocytes and Provide

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    Cytotoxic T cells = Tcytv Recognize virus-infected cellsv Kill infected cells directly by inducing

    apoptosis (programmed cell death cellsuicide)

    v MHC class I-restricted

    Natural Killer Cells

    Recognize virus-infected cells and cancer cells

    They directly release lethal chemicals, leading to

    apoptosis

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    Helper T cellsParticipate in both the Humoral and Cell-Mediated Immune Responses

    The HIV virus attacks Helper T cells

    Slide 31 of 46

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    T- cell receptorEach T cell receptor consists of two different

    polypeptide chains.

    The tips of the chain form a variable (V) region; the

    rest is a constant (C) region.

    T cells can bind to an antigen that is free or on the

    surface of a pathogen

    A single T cell has about 100,000 identical antigen

    receptors.

    Fig 43 9

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    Fig. 43-9

    Anti gen-

    binding

    site

    Antigen-

    bindingsite

    Antigen-

    binding

    site

    Disulf ide

    bridge

    Variabl

    eregions

    Constant

    regions

    Transmembrane

    region

    Plasma

    membra

    ne

    Light

    chain

    Heavychains T c

    ell

    ch

    ain

    ch

    ain

    DisulfidebridgeCytoplasm of T cell

    (b) T cellreceptor

    Cytoplasm of B cell(a) B cell

    receptor

    B cell

    V V

    C C

    V V

    C C C C

    VV

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    Steps of the Cell MediatedResponse

    1. Infected cell presents antigen on ClassI MHC

    2. Cytotoxic T Cell recognizes antigenand binds to it

    Slide 27 of 46

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    Steps of the Cell MediatedResponse

    3 . Cytotoxic T Cell reproduces (clonesitself)

    4. Cytotoxic T Cells bind to antigen boundto infected cells and release perforin

    to lyse infected cells

    Slide 28 of 46

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    Response to InfectedCells

    Cytotoxic T cells are the effector cells in cell-mediatedimmune response.

    Cytotoxic T cells make CD8 , a surface protein that

    greatly enhances interaction between a target cell and

    a cytotoxic T cell.

    Binding to a class I MHC complex on an infected cell

    activates a cytotoxic T cell and makes it an active killer.

    The activated cytotoxic T cell secretes proteins that

    destroy the infected target cell.

    Fig 43-17

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    Fig. 43 17

    Antigen-

    presenting

    cell

    Peptideantigen

    Cell-mediated

    immunity(attack

    oninfected

    cells)

    Class II MHC

    moleculeC D4

    TCR (T cellreceptor)Helper T

    cellHumoral

    immunity(secretio

    n of antibodies by

    plasmacells

    )

    Cytotoxic Tcell

    Cytokines

    Bcell

    Bacterium

    +

    + +

    +

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    Memory T-cells

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    Overall diagramatic presentation of cell mediated immunity

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    Primary versus SecondaryResponse

    Primary Response = initial immune

    response to antigen -

    The first exposure to a specific antigen represents theprimary immune response

    During this time, effector B cells called plasma cells

    are generated, and T cells are activated to theireffector forms

    Secondary Response = immune response when-

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    Primary vs. SecondaryResponse

    The secondary response is much faster than theprimary response

    More antibody & T cell production in a shorteramount of time

    Primary

    response

    Secondary Response

    Slide 30 of 46

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    Thanks