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The Humoral Adaptive Immunity Susanna Hilda Hutajulu Basic Immunology Course Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta April, 24, 2012 [email protected]

7. Imunitas Adaptif Humoral

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  • The Humoral Adaptive Immunity

    Susanna Hilda Hutajulu

    Basic Immunology Course

    Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta

    April, 24, 2012

    [email protected]

  • Antibody-mediated Immunity

    Toxin-induce disease Viral infectionBacterial infection

    Definition of humoral adaptive immunity

  • Humori (Latin) = fluid.

    adoptively transferred by serum

    mediated by soluble antibody molecules that float

    in biological fluids.

    Soldiers of the battle in

    human immune response:

    B cells

    Antibodies

  • B cell maturation takes place in bone marrow, B cell activation takes place in secondary lymphoid organs.

  • Antibody structure

    Fab fragment

    Fc fragment

  • Antibody contributes to immunity in 3 ways:

    - neutralization- opsonization- complement activation

  • Topic outlines

    1. B cell activation induce antibody secretion

    2. The distribution and functions of immunoglobulin classes

    3. The destruction of antibody-coated pathogens via Fc receptor

  • 1. B cell activationThe initiation of humoral immune response

    Generally requires antigen-specific T cell help.

    Help from Th cell will come after antigen processing.

    Link recognition.

  • Second signal is always required for B cell activation

    Thymus-dependent antigen (T helper cell activation)- 1st signal: crosslinking of BCR- 2nd signal come from T helper cell

    Thymus-independent antigen- 1st signal: crosslinking of BCR- 2nd signal: direct binding of antigen to

    innate receptor or massive crosslinking of IgM membrane by polimeric antigen

  • Helper T cells activate B cells that recognize the same antigen (= link recognition).

  • The humoral immune response is initiated when B cells that bind antigen are signaled by helper T cells

    Activation of TH cell:1. Expression of CD40-L2. Membrane-bound 3. Synthesis and secretion of cytokines

  • B cell activation takes place in secondarylymphoid organs.

  • Activated B cells migrate into follicles and proliferate to form germinal centers (GCs).

  • GC B cells undergo:

    Proliferation Somatic hypermutation of V region

    (improved affinity for antigens) Selection for high affinity BCR Isotype switching Differentiation into plasma cells and

    memory cells

  • B cell activation results in high-affinity antibody-secreting plasma cells and high affinity memory B cells.

  • GC B cells undergo class switching

    Every B cell begins by expressing IgM as its cell receptor, the first antibody produced in immune response is always IgM.

    In isotype switching, immune response may express IgG, IgA or IgE.

    Class switching is stimulated by cytokines (released by T cells) or mitogenic signal (from pathogen).

  • Characteristics of Ig isotypes

    The number and location of interchain disulfide bonds

    The number of attached oligosaccharide moieties.

    The number of C domain

    The length of hinge region.

    Fc fragment

    Fab fragment

    H= heavy chainL= light chain

  • GC B cells undergo class switching, preceded by

    transcriptional activation of heavy chain region genes.

  • Class switching is directed by cytokines.

  • Thymus-independent antigens

    Bacterial antigens which have ability to activate B cells, do not require T cell help.

    Special properties of some bacterial polysaccarides, polimeric proteins, and lypopolysaccarides enable them to stimulate B cells.

    Two classes: TI type 1 intrinsic activity (+) TI type 2 intrinsic activity (-)

  • TI-1 antigens can directly induce B cell division without T cell help (= B cell mitogen, induces cells to

    undergo mitosis).

  • B cell class switching by TI-2 is enhanced by cytokines.

    DC may be able to bind innate receptor, secrete TNF fam cytokine and activate class switching.

  • Example of different classes of antigen that elicit

    antibody responses.

  • 2. Distribution and function of immunoglobulin classes

    Extracellular pathogens are in most sites in the body antibodies must be equally widely distributed to combat them.

    Distribution is determined by their isotypes.

  • IgG: extracelluler fluid, fetus (by transplacental transport)

    IgM: >> plasma

    IgA:monomeric: extracelluler fluid dimeric: in secretion across epithelia

    IgE is beneath epithelial surface(respiratory, gastrointestinal, skin)

    Brain is normally devoid of Ig.

    Antibodies of different classes operate in

    distinct places and have distinct effector functions.

  • Functions of Ig isotypes

  • Function of antibody

  • Neutralization= High-affinity IgG and IgA antibodies can neutralize bacterial toxins

  • Neutralization= High-affinity IgG and IgA antibodies can inhibit the infectivity of viruses.

  • Antibodies blocks adherence

    of some bacteria.

  • Antibody:antigen complexes activate the classical pathway of complement

    enhance opsonization and lyse some bacteria.

  • 3. The destruction of antibody-coated pathogens via Fc receptors

    Many pathogens do not bind to neutralizing targets on pathogen surface

    need to be linked to

    Fc receptor.

  • Cells bearing Fc receptor:

    Phagocytic cells (neutropil, macrophage)

    Non-phagocytic secrete mediator when their FcRare engaged NK cells

    eosinophil

    basophil

    mast cells

  • The Fc receptors are signaling receptors specific for

    immunoglobulins of different classes.

  • Fc receptors activate NK cells to destroy

    antibody-coated targets in antibody-dependent cell-mediated cytotoxicity (ADCC).

  • Mast cells and basophils bind IgE antibody via the high-affinity Fc receptor.

  • Fc receptors on phagocytes facilitate phagocytosis

    to ingest and destroy pathogens.

  • Clearance of immune complex from circulation

  • Summary

    Human immune response involves antibody production the binding of antibody-pathogen elimination by phagocytic cells and other molecules

    The antibody production usually requires Th cells help but certain pathogen can stimulate B cells independently.

    Roles of antibody include neutralization, opsonization and complement activation.

  • Thank you