IRCelular11 (stu)

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    Objectives

    After working through this module, you should

    be able to:

    Explain the mechanisms involved in cellular

    immunity.

    Explain the interaction between the

    components of the immune system in regulating

    immune response.

    Describe the mechanism of immune response

    towards superantigen

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    Cellular Immune Response

    While humoral immune response is for

    extracellular bacterial, cellular immune

    response is more for intracellular bacteria,

    viruses, tumours and transplants.

    Cells involved in specific cellular immune

    response are the T lymphocytes

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    Lymphocyte ActivationMacrophage

    NK cell

    TH2TH1

    IFN-

    IL-12IFN-

    Il-12, TNF-

    IFN-

    Il-4, IL-10

    Cross-regulation

    Promotes cellular immunity Promotes humoral immunity

    IL-4

    IL-5IL-6

    IL-10

    IL-13

    IL-2

    IFN-TNF-

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    Antigen Elimination

    The elimination ofantigens in the effector phase ofspecific immune responses occurs by the cooperativeactions of differentiated lymphocytes and defence

    mechanisms of innate immunity

    In cell-mediated immunity, activated T lymphocytessecrete cytokines, which enhance the functions of

    phagocytes and other inflammatory leukocytes

    However, cytotoxic T cells do not require other

    cooperating mechanisms to eradicate microbes

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    Antigen Elimination

    Cellular Immunity

    Microbe (bacteria)surviving in phagocyte

    MHC-II

    CD4 recognizesexogenous antigen

    Activation of microbicidalfunctions of phagocyte

    MHC-I

    CD8 recognizes

    endogenous antigen Lysis of infected cell

    Microbe (virus) infecting

    non-phagocytic cell

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    Regulation of Immune Response

    The immune response has to be regulated and

    brought back to the normal status as excessiveresponse will be detrimental to the body.

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    Immunoregulation

    Y Y Y

    Y Y Y

    Antigen

    Macrophage IL-1

    Suppresor T cell

    IL-2

    IL-1

    Helper T cellStimulation

    B cell

    Feedback

    inhibition

    Idiotype network

    interactions

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    Regulation of Immune Response

    Based on the diagram above, themechanisms of immunoregulation.

    1.Control by antigen

    level of exogenous antigen intensityof response

    2.Feedback control by antibodyIgG inhibit responses via Fc receptor on

    B-cells

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    Regulation of Immune Response

    3. T-cell regulation

    a. activated T-cells express Fas and FasL

    which restrain unlimited clonal expansion

    Fas-mediated apoptosis of activatedmature cells

    b. mutual inhibition between TH1 and TH2cells suppression

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    Regulation of Immune Response

    4. Idiotype networks

    antigen-specific receptors on lymphocytes

    can interact with the idiotypes on thereceptors of other lymphocytes to form anetwork (Jerne)

    5. Genetic factors

    10 genes control overall antibody response

    affecting

    - macrophage ag processing

    - microbicidal activity

    - rate of proliferation of differentiating

    B-cells

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    Regulation of Immune Response

    6. Immunoneuroendocrine networks

    - interaction among immunologic, neurologic

    and endocrinologic systems

    - regulatory interdependent circuits feedback by cytokines augmentingproduction of corticosteroids shutsdown TH1 and macrophage activity

    - estrogens largely responsible for the moreactive responses in females relative to

    males

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    Regulation of Immune Response

    7. Effects of diet and other factors on

    immunity

    - protein-calorie malnutrition impairs

    - exercise

    - trauma

    - age: IL-2, TNF, IL-1, IL-6

    - environmental pollution

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    SUPERANTIGEN

    ACTIVITY 1

    Based on the diagrams below, how is

    superantigen different from normal antigenin antigen recognition and stimulating animmune response?

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    macrophage

    lymphocytelymphocyte

    macrophage

    antigen

    TCR TCR

    Antigen piece

    MHC II MHC II

    ANTIGEN SUPERANTIGEN

    V V V V

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    References

    Stites DP, Terr Al and Parslow TG. Medical Immunology. 10th Edition,Appleton & Lange, Prentice-hall International Inc. 2001.

    Roitt I, Brostoff J and Male D. Immunology. 6th Edition, GowerMedical Publishing, London. 2001

    Geo.F.Brooks, Janet S.Butel and Stephen A.Morse. Jawetz, Melnick,

    & Adelbergs Medical Microbiology. 23rd Edition, McGraw-Hill. 2004.

    Cedric Mims, Hazel M. Dockrell, Richard V.Goering, Ivan Roitt, DerekWakelin and Mark Zuckerman. Medical Microbiology. 3rd Edition,Elsevier Mosby. 2004.

    Marjorie Kelly Cowan and Kathleen Park Talaro. Microbiology ASystems Approach. McGraw-Hill. 2006.