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    AUTOIMMUNITY

    Uploaded by

    Francesc Oktofabregas
    B cell and T cell tolerance are processes that involve the failure of B or T cells to respond to self antigens. Mechanisms of central tolerance include clonal deletion, where immature B or T cells are eliminated after binding self antigen, and clonal anergy, where mature cells are unable to respond even after antigen binding. Breaking of tolerance can occur via molecular mimicry, polyclonal activation of B or T cells, or exposure of hidden self antigens and may play a role in autoimmune diseases like rheumatoid arthritis, rheumatic fever, and diabetes mellitus type 1.

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    AUTOIMMUNITY

    Uploaded by

    Francesc Oktofabregas
    131 views36 pages
    B cell and T cell tolerance are processes that involve the failure of B or T cells to respond to self antigens. Mechanisms of central tolerance include clonal deletion, where immature B or T cells are eliminated after binding self antigen, and clonal anergy, where mature cells are unable to respond even after antigen binding. Breaking of tolerance can occur via molecular mimicry, polyclonal activation of B or T cells, or exposure of hidden self antigens and may play a role in autoimmune diseases like rheumatoid arthritis, rheumatic fever, and diabetes mellitus type 1.

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    B cell and T cell tolerance are processes that involve the failure of B or T cells to respond to self antigens. Mechanisms of central tolerance include clonal deletion, where immature B or T cells are eliminated after binding self antigen, and clonal anergy, where mature cells are unable to respond even after antigen binding. Breaking of tolerance can occur via molecular mimicry, polyclonal activation of B or T cells, or exposure of hidden self antigens and may play a role in autoimmune diseases like rheumatoid arthritis, rheumatic fever, and diabetes mellitus type 1.

    Copyright:

    © All Rights Reserved
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    131 views36 pages

    AUTOIMMUNITY

    Uploaded by

    Francesc Oktofabregas
    B cell and T cell tolerance are processes that involve the failure of B or T cells to respond to self antigens. Mechanisms of central tolerance include clonal deletion, where immature B or T cells are eliminated after binding self antigen, and clonal anergy, where mature cells are unable to respond even after antigen binding. Breaking of tolerance can occur via molecular mimicry, polyclonal activation of B or T cells, or exposure of hidden self antigens and may play a role in autoimmune diseases like rheumatoid arthritis, rheumatic fever, and diabetes mellitus type 1.

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    © All Rights Reserved
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    Download as ppt, pdf, or txt
    of 36

    AUTOIMMUNITY

    B Cell Tolerance
    T Cell Tolerance
    Clonal Deletion
    Clonal Anergy
    Immunogen vs Tolerogen
    Mechanism of breaking B and T
    Cell`Tolerance

    B CELL TOLERANCE
    Sel B menghasilkan antibodi untuk apa saja yang
    tidak normal ada dalam tubuh
    Mengenal antigen melalui resptor (IgM.IgD) yang
    sudah ada pada sel B mature yang bisa
    menangkap jutaan jenis antigen.
    Bagaimana proses seleksi dalam BM waktu
    pematangan sel B tidak jelas seperti pematangan
    sel T di Timus.
    Sel B tidak berespons terhadap antigen self
    disebut tolerance (normal), tetapi B Cell
    Tolerance dimaksudkan juga jika tidak berespon
    terhadap antigen asing (abnormal)

    B or T CELL TOLERANCE
    is a process that involves the faillure of B or T cell to respond
    to self antigens (normal) or foreign antigens (abnormal)
    CLONAL DELETION
    This process involved the elimination of immature B or
    T cells after antigen binds to their receptor.
    CLONAL ANERGY
    This process involves the inability of mature B or T cells
    to respond to antigen even after it binds to
    its receptor.
    IMMUNOGEN
    The antigen is called an immunogen if it induces
    activation of a B or T cell
    TOLEROGEN
    The antigen is called tolerogen if it does not activate
    a B or T cell (Its induce B or T cell clonal anergy).

    B CELL TOLERANCE

    Stem Cell

    Pro-B

    Pre-B

    Bone Marrow

    Immature B Mature B Effector B


    Peripheral lymphoid
    organ or tissue

    No antigen dependence
    RAG-1 and RAG-2

    Receptor Editing

    IgM,IgD

    Self antigen Foreign antigen


    Selection

    Clonal Deletion
    (apoptosis)

    CentralTolerance

    Performance
    effector
    function.

    Clonal anergy

    Peripherial Tolerance

    B CELL TOLERANCE
    SELF ANTIGENS

    IgM
    B

    IgD
    Th

    Immature

    IgM
    B

    Th

    Mature

    CLONAL ANERGY
    Polyclonal activation

    CLONAL DELETION

    ACTIVATED CLONE

    DEATH
    AUTOIMMUNE

    SELECTION OF IMMATURE B CELLS


    (CLONAL SELECTION)

    IgM
    B

    AUTOIMMUNE DISEASE
    IgD
    B

    Immature B cells

    Self Antigen

    IgM

    IgM
    Mature B cells

    Self Antigen
    IgM

    IgD
    B

    Immature B cells

    apoptosis
    (Negative Selection)

    Cell Activation
    AUTOIMMUNE

    Idiotype
    (cdr)

    Millions of proteins
    (self & foreign)
    H-Chain

    Fab

    Fc

    Constan
    portion
    (merah)

    Variable
    portion
    (biru)

    L-Chain

    papain

    Antigen
    Binding Site

    -s-sRAG-1 & RAG-2


    (Bone Marrow stage)

    B CELL TOLERANCE IN BONE MARROW


    Autoreactieve B Cells (Expression of chain)
    Reactivate expression of RAG-1 & RAG-2
    recombinese proteins. (rearranging light chain genes)
    -deleting element
    (sejumlah segmen gen hilang)
    Assemble a new & gene
    (Receptor Editing)

    Fail of Receptor Editing

    No autoreactivity
    Release from Bone Marrow
    to peripherial lymphoid organ

    death
    (apopthosis)

    T CELLS TOLERANCE

    TCR

    Stem Cell Pro-T Pre-T Immature T Mature T Naive mature T


    BM

    Periphery

    Thymus
    No respon to antigen

    Pos&Neg selection (self ant)

    activation by
    Foreign ant

    RAG 1 & RAG 2 expression


    Clonal Deletion
    (apoptosis)

    T cell regulator Clonal anergy

    CentralTolerance

    Peripherial Tolerance

    T CELL ANERGY

    CTLA-4

    anergy

    B CELL TOLERANCE
    is a process that involves the faillure of B cell to respond to
    self (normal) or foreign (abnormal) antigen.
    CLONAL DELETION
    This process involved the elimination of immature B cells
    after antigen binds to their immunoglobulin receptor.
    CLONAL ANERGY
    This process involves the inability of mature cells
    to respond to antigen even after it binds to
    its immunoglobulin receptor.
    IMMUNOGEN
    The antigen is called an immunogen if it induces
    activation of a B cells
    TOLEROGEN
    The antigen is called tolerogen if it does not activate
    a B cell (Its induce B cell clonal anergy).

    MECHANISM FOR BREAKING


    B AND T CELL TOLERANCE

    MOLECULAR MIMICRY
    POLYCLONAL
    B CELL ACTIVATION
    POLYCLONAL
    T CELL ACTIVATION
    EXPOSURE OF HIDDEN
    SELF ANTIGEN

    THE ROLE OF INFECTION IN THE


    DEVELOPMENT OF AUTOIMMUNITY :

    MOLECULAR MIMICRY
    IgD

    IgM

    Streptococcus
    Antigen (epitop)

    Streptococcus
    antibody

    Cross
    Reaction

    epitop on
    heart cells

    Destruction of heart tissue


    RHEUMATIC FEVER

    THE ROLE OF INFECTION IN THE


    DEVELOPMENT OF AUTOIMMUNITY :

    POLYCLONAL STIMULANT
    LIPOPOLISACHARIDE (LPS)

    IgD

    IgM

    IgD

    Th

    IgM
    B

    Self Antigen
    (heart,Kidney,
    Insulin,Lung)
    ANERGIZED B CELLS

    Stimulatory signal
    Cytokine
    ACTIVATED B CELLS
    Anti heart Antibody
    Anti kidney Antibody
    Anti Insulin Antibody
    Anti Lung Antibody

    Anti LPS Antibody

    THE ROLE OF INFECTION IN THE


    DEVELOPMENT OF AUTOIMMUNITY :

    POLYCLONAL STIMULANT
    SUPERANTIGEN OF BACTERIA

    IgD
    APC

    Th

    IgM
    B

    Self Antigen
    (heart,Kidney,
    Insulin,Lung)
    ANERGIZED B CELLS

    Stimulatory signal
    Cytokine
    ACTIVATED B CELLS
    Anti heart Antibody
    Anti kidney Antibody
    Anti Insulin Antibody
    Anti Lung Antibody

    HLA link immunolgic


    Disease
    Disease
    HLA allele RR
    Rheumatoid Arthritis DR4
    4
    Insulin-Dep Diabetes DR3
    5
    DR4
    5
    DR3/DR4 25
    Multiple sclerosis
    DR2
    4
    SLE
    DR2/DR3 5
    Pemphigus vulgaris
    DR4
    14
    Ankylosing Spondylitis B27
    90-100

    AUTOIMMUNITY
    B Cell Tolerance
    T Cell Tolerance
    Clonal Deletion
    Clonal Anergy
    Immunogen vs Tolerogen
    Mechanism of breaking B and T
    Cell`Tolerance

    B CELL TOLERANCE

    Stem Cell

    Pro-B

    Pre-B

    Bone Marrow

    Immature B Mature B Effector B


    Peripheral lymphoid
    organ or tissue

    No antigen dependence
    RAG-1 and RAG-2

    Receptor Editing

    IgM,IgD

    Self antigen Foreign antigen


    Selection

    Clonal Deletion
    (apoptosis)

    CentralTolerance

    Performance
    effector
    function.

    Clonal anergy

    Peripherial Tolerance

    B CELL TOLERANCE
    SELF ANTIGENS

    IgM
    B

    IgD
    Th

    Immature

    IgM
    B

    Th

    Mature

    CLONAL ANERGY
    Polyclonal activation

    CLONAL DELETION

    ACTIVATED CLONE

    DEATH
    AUTOIMMUNE

    T CELLS TOLERANCE

    TCR

    Stem Cell Pro-T Pre-T Immature T Mature T Naive mature T


    BM

    Periphery

    Thymus
    No respon to antigen

    Pos&Neg selection (self ant)

    activation by
    Foreign ant

    RAG 1 & RAG 2 expression


    Clonal Deletion
    (apoptosis)

    T cell regulator Clonal anergy

    CentralTolerance

    Peripherial Tolerance

    T CELL ANERGY

    CTLA-4

    anergy

    B CELL TOLERANCE
    is a process that involves the faillure of B cell to respond to
    self (normal) or foreign (abnormal) antigen.
    CLONAL DELETION
    This process involved the elimination of immature B cells
    after antigen binds to their immunoglobulin receptor.
    CLONAL ANERGY
    This process involves the inability of mature cells
    to respond to antigen even after it binds to
    its immunoglobulin receptor.
    IMMUNOGEN
    The antigen is called an immunogen if it induces
    activation of a B cells
    TOLEROGEN
    The antigen is called tolerogen if it does not activate
    a B cell (Its induce B cell clonal anergy).

    MECHANISM FOR BREAKING


    B AND T CELL TOLERANCE

    MOLECULAR MIMICRY
    POLYCLONAL
    B CELL ACTIVATION
    POLYCLONAL
    T CELL ACTIVATION
    EXPOSURE OF HIDDEN
    SELF ANTIGEN

    THE ROLE OF INFECTION IN THE


    DEVELOPMENT OF AUTOIMMUNITY :

    MOLECULAR MIMICRY
    IgD

    IgM

    Streptococcus
    Antigen (epitop)

    Streptococcus
    antibody

    Cross
    Reaction

    epitop on
    heart cells

    Destruction of heart tissue


    RHEUMATIC FEVER

    THE ROLE OF INFECTION IN THE


    DEVELOPMENT OF AUTOIMMUNITY :

    POLYCLONAL STIMULANT
    LIPOPOLISACHARIDE (LPS)

    IgD

    IgM

    IgD

    Th

    IgM
    B

    Self Antigen
    (heart,Kidney,
    Insulin,Lung)
    ANERGIZED B CELLS

    Stimulatory signal
    Cytokine
    ACTIVATED B CELLS
    Anti heart Antibody
    Anti kidney Antibody
    Anti Insulin Antibody
    Anti Lung Antibody

    Anti LPS Antibody

    THE ROLE OF INFECTION IN THE


    DEVELOPMENT OF AUTOIMMUNITY :

    POLYCLONAL STIMULANT
    SUPERANTIGEN OF BACTERIA

    IgD
    APC

    Th

    IgM
    B

    Self Antigen
    (heart,Kidney,
    Insulin,Lung)
    ANERGIZED B CELLS

    Stimulatory signal
    Cytokine
    ACTIVATED B CELLS
    Anti heart Antibody
    Anti kidney Antibody
    Anti Insulin Antibody
    Anti Lung Antibody

    HLA link immunolgic


    Disease
    Disease
    HLA allele RR
    Rheumatoid Arthritis DR4
    4
    Insulin-Dep Diabetes DR3
    5
    DR4
    5
    DR3/DR4 25
    Multiple sclerosis
    DR2
    4
    SLE
    DR2/DR3 5
    Pemphigus vulgaris
    DR4
    14
    Ankylosing Spondylitis B27
    90-100

    AUTOIMMUNE DISEASES
    Rheumatoid Arthritis (antinuclear antibody)
    Rheumatic Fever (antistreptococcus antibody)
    Goiter(antibody against thyroid epithelial cells)
    Diabetes Mellitus type I (antibody against
    materials of cytoplasm/cell membrane of
    pancreas cell, cytotoxicity of T cell to cell).
    Chronic Thyroiditis (Hashimoto), (B and T cell
    infiltration)
    Scleroderma (antinuclear antibody)

    Contoh-contoh penyakit otoimun


    Artritis reumatoid (antinuclear antibody)
    Demam Reuma (antibodi thd streptococcus)
    Goiter (antibodi terhadap epitel tiroid)
    Diabetes Mellitus tipe I (antibodi terhadap
    bahan sitoplasma dan membran sel Beta
    Pankreas dan sitotoksitas sel T terhadap el
    Beta Pankreas).
    Tiroiditis kronis(Hashimoto) (infiltrasi sel T&B)
    Scleroderma (antinuclear antibody)

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