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    Determinants of Antigenicity and Immunogenicity

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    powek
    1. Several factors determine the immunogenicity of an antigen, including properties of the immunogen itself, properties of the host, and the mode of antigen exposure. 2. Properties of the immunogen that influence immunogenicity include its molecular size, chemical composition, ability to be processed and presented by MHC molecules, and level of foreignness to the host. 3. Properties of the host that influence immunogenicity include its genetic factors like MHC genotype and genes encoding antigen receptors and immune regulation. The physiological condition of the host also contributes. 4. The mode of antigen exposure, including dosage, route of administration, and use of adjuvants can also impact the immunogenicity of an antigen.

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    Determinants of Antigenicity and Immunogenicity

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    powek
    24 views20 pages
    1. Several factors determine the immunogenicity of an antigen, including properties of the immunogen itself, properties of the host, and the mode of antigen exposure. 2. Properties of the immunogen that influence immunogenicity include its molecular size, chemical composition, ability to be processed and presented by MHC molecules, and level of foreignness to the host. 3. Properties of the host that influence immunogenicity include its genetic factors like MHC genotype and genes encoding antigen receptors and immune regulation. The physiological condition of the host also contributes. 4. The mode of antigen exposure, including dosage, route of administration, and use of adjuvants can also impact the immunogenicity of an antigen.

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    Documento sobre antígenos

    Original Title

    1. Antigens

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    1. Several factors determine the immunogenicity of an antigen, including properties of the immunogen itself, properties of the host, and the mode of antigen exposure. 2. Properties of the immunogen that influence immunogenicity include its molecular size, chemical composition, ability to be processed and presented by MHC molecules, and level of foreignness to the host. 3. Properties of the host that influence immunogenicity include its genetic factors like MHC genotype and genes encoding antigen receptors and immune regulation. The physiological condition of the host also contributes. 4. The mode of antigen exposure, including dosage, route of administration, and use of adjuvants can also impact the immunogenicity of an antigen.

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    © All Rights Reserved
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    24 views20 pages

    Determinants of Antigenicity and Immunogenicity

    Uploaded by

    powek
    1. Several factors determine the immunogenicity of an antigen, including properties of the immunogen itself, properties of the host, and the mode of antigen exposure. 2. Properties of the immunogen that influence immunogenicity include its molecular size, chemical composition, ability to be processed and presented by MHC molecules, and level of foreignness to the host. 3. Properties of the host that influence immunogenicity include its genetic factors like MHC genotype and genes encoding antigen receptors and immune regulation. The physiological condition of the host also contributes. 4. The mode of antigen exposure, including dosage, route of administration, and use of adjuvants can also impact the immunogenicity of an antigen.

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    Determinants of antigenicity and

    immunogenicity
    Molecular entities recognized by lymphocytes

    • Antigen: any molecule that is specifically recognized by an antibody


    or a T-cell receptor (TCR)

    • Immunogen: the type of antigen that evokes an adaptive immune


    response

    • Hapten: a non-immunogenic molecule (often with low molecular


    weight) that can be made immunogenic by conjugation to a suitable
    carrier
    • Epitope: the portion of an antigen that is
    recognized and bound by an Ab or TCR
    (antigenic determinant) Epitope
    interacts with
    paratope
    • Paratope: The site of an antibody or a TCR that
    binds to an epitope on an antigen
    The B cell is the one that is going
    to be linked if the hapten is
    conjugated with a protein carrier
    NO2

    NO2 =

    Dinitrophenyl (DNP) hapten

    Large protein (carrier)

    Immunization Induction of Antibodies

    DNP No

    Protein-conjugated DNP Yes


    What Determines Immunogenicity of an Antigen?
    type of ag that
    1. Properties of the Immunogen evokes an
    adaptive inmune
    response

    2. Properties of the Host


    a. Genetic :
    - Antigen presentation (MHC)
    - Genes encoding antigen receptors
    - Genes Coding for Immune Regulation
    b. Physiological: Condition of the Host

    3. Mode of Antigen Exposure


    1. Contribution of the immunogen to immunogenicity

    • Nature of the antigen: type of molecule


    Ab  Humoral: proteins >polysaccharides>>>>lipids>nucleic acids
    T cell  Cellular: proteins and some lipids

    • Features of the immunogen:

     Foreignness
     Molecular size
     Chemical composition and complexity
     Ability to be processed and presented by a MHC molecule
    1. Contribution of the immunogen to immunogenicity
    The more different the
    BSA: Bovine serum albumin animal is, the more
    probabable is to develope an
    inmune reponse

    • Foreignness

    - +
    • Molecular size: The best immunogens tend to
    have a molecular mass approaching 100,000
    daltons (Da) The higer the size, the higuer
    posibility to find a T epitope

    • Chemical composition and heterogeneity

    Synthetic homopolymers, containing a single Aa


    or a sugar, poor immunogenicity regardless the
    size.
    The addition of aromatic Aa, (Tyr, Phe) enhances
    immunogenicity

    • Ability to be processed and presented by a


    MHC molecule
    1. Contribution of the immunogen to immunogenicity
    Levels of protein organization

    All four levels contributes to structural complexity of a protein and hence


    affects its immunogenicity.
    1. Contribution of the immunogen to immunogenicity
    Susceptibility to antigen processing and presentation

    What is seen by T lymphocytes in an Ag? Ag/MHC

    La primera proteína se tiene que


    degradar y luego unirse al MHC.

    Degradación Unión al MHC

    Major histocompatibility complex


    molecules
    2. Contribution of the host to immunogenicity

    MHC = MLA
    • Genotype of the host: antigen presentation by MHC products
    Algunas personas cuando les vacunan
    de Hepatitis B, generan Ab. Otras no lo
    hacen. Depende de la genética

    PROCESSING
    PRESENTATION

    Antigen Presentation
    processing by MHC molecules

    MHC: THE MOST


    MHC coge un trozo de algo malo de dentro de la
    POLIMORPHIC
    célula. Se pone en la membrana con el trozo
    MOLECULE IN THE BODY
    para que un linfocito pueda ver si es algo malo y
    MHC is a hapten because
    comérselo.
    without the union of the
    peptide is not inmunogenic
    2. Contribution of the host to immunogenicity

    • Genotype of the host: antigen receptors

    Individual A

    Individual B

    • Genes coding for immune regulation

    • Physiological condition of the host: immune competence (genetic deficiencies,


    disease, therapies….)
    3. Contribution of the biological system to immunogenicity:
    Mode of antigen exposure

    • Immunogen dosage and route of administration


    o Insufficient dosage to induce an immune response
    o Too much dosage: induction of tolerance (unresponsive state)

    Route of administration:
    o Oral
    o Intradermal
    o Subcutaneous
    o Intramuscular
    o Intraperitoneal
    o Intravenous
    3. Contribution of the biological system to immunogenicity:
    Mode of antigen exposure-adjuvants

    • Adjuvants Helpers

    o Immune stimulants:
     ↑ co-stimulatory signals
     lymphocyte proliferation

    o Vehicle depot: Depósito de vehículos


     ↑ prolong antigen persistence
     Targeting to APC
    NO ENTRA
    Epitopes
    Immunologically active regions of an antigen that bind to antigen-specific membrane
    receptors on lymphocytes or to secreted antibodies

    • Properties of B-cell epitopes recognised by ab


    • Properties of T-cell epitopes recognised by MHC

    Ig + Ag TCR + Ag + MHC
    Properties of B-cell epitopes

    Size: no larger than the size of the


    antibody-binding site

    Chemical properties: generally


    hydrophilic amino acids (exposed on the
    protein surface and topographically
    accessible to antibodies

    Location on Ags: sequential or non-


    sequential amino acids
    In flexible regions of an immunogen
    and displaying site mobility

    Conformation: Antibodies
    recognize epitopes in native
    conformation
    not T cells, that
    can be
    recognized
    linear peptides
    Properties of B-cell epitopes
    Sequence-based methods
    for prediction of linear epitopes

     Protein hydrophobicity – hydrophilicity algorithms ALGORITHMS


    - Hydrophilicity
     Protein flexibility prediction algorithm - Flexibility
    - Secondary
    structure
     Protein secondary structure prediction algorithms - Antigenicity

     Protein “antigenicity” prediction

    TSQDLSVFPLASCCKDNIASTSVTLGCLVTG
    YLPMSTTVTWDTGSLNKNVTTFPTTFHETY
    GLHSIVSQVTASGKWAKQRFTCSVAHAEST
    AINKTFSACALNFIPPTVKLFHSSCNPVGDT
    HTTIQLLCLISGYVPGDMEVIWLVDGQKATN
    IFPYTAPGTKEGNVTSTHSELNITQGEWVSQ
    KTYTCQVTYQGFTFKDEARKCSESDPRGVT
    SYLSPPSPL
    Posible epitope
    location

    Kyte & Doolittle hydropathy plot of


    Hopp & Woods antigenicity plot of Alcohol
    Alcohol Dehydrogenase
    Dehydrogenase. The regions with the highest
    values are the most hydrophilic and indicate
    potential epitope locations for antigens
    Properties of T-cell epitopes

    • T cells recognize antigens previously


    processed into antigenic peptides that bind
    to MHC molecules

    • Prediction algorithms based on these


    properties
    Ag are previously processed so
    T cells can recognize them and
    bind them to MHC molecules
    Applications of antigenicity and immunogenicity
    characterization
    • Diseño de vacunas y optimización:
    -Preparación de vacunas mejoradas.
    • Herramientas para monitorear respuestas inmunes
    adaptativas:
    • Vaccine design
    -Perfil deland optimization
    estado inmune de individuos y pacientes.
    o Preparation
    -Monitoreoofdel
    improved vaccines
    efecto de los tratamientos asociados con IR.
    • Generación de anticuerpos contra los depósitos deseados:
    -Anticuerpos terapéuticos.
    • Tools for -Anticuerpos
    monitoring adaptive
    para immune
    aplicaciones técnicas.responses
    o Profiling
    • Diseñoofdeimmune
    drogas: status of individuals and patients
    -Preparación de medicamentos no inmunogénicos.
    o Monitoring the effect of treatments associated wit IR

    • Generation of antibodies against desired epitopes


    o Therapeutic antibodies
    o Antibodies for technical applications

    • Drug design
    o Preparation of non-immunogenic drugs

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