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Chapter 4 Antigen(Ag)

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Chapter 4 Antigen(Ag * * * * * * * * * * * Functional determinant: epitope existed on the surface of Ag which can be recognized by BCR or combined with Ab easily. – PowerPoint PPT presentation

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Title: Chapter 4 Antigen(Ag)


1
  • Chapter 4 Antigen(Ag)

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Contents
  • Part? Introduction
  • Part? Factors Affecting Immunogenicity
  • Part? Specificity and Cross-Reaction of Antigens
  • Part? Classification of Antigens
  • Part? Important Antigens in Medicine
  • Part? Superantigen and Adjuvants

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Part? Introduction
  • ?. Definition
  • Antigen(Ag) An antigen is a substance that can
    stimulate immune system to produce a specific
    immune response, and can react specifically with
    the products of the immune response in vitro or
    in vivo.
  • Products of the immune response antibodies
    and/or effector lymphocytes.

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  • B cells Antibody
  • Ag
  • T cells Effector T
    cells

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Key points
  • Stimulate immune system to produce a specific
    immune response.
  • React specifically with the products of the
    immune response in vitro or in vivo.

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  • ?. Properties of antigens
  • 1. Immunogenicity
  • An ability to stimulate the body to evoke a
    specific immune response.
  • Immunogens substances with immunogenicity
  • 2. Immunoreactivity
  • Antigenicity
  • An ability to combine with
    corresponding Ab or sensitized T lymphocyte.

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1.Immunogenicity to induce the specific immune
response.
T
T
Ag
B
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2. Immunoreactivity to combine with
corresponding Ab or sensitized T lymphocyte

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  • ?. Complete antigen and hapten
  • 1. Complete antigen
  • Both Immunogenicity and Immunoreactivity.
  • 2. Hapten
  • Only Immunoreactivity.
  • Haptencarrier complete antigen
  • Carrier enhance the immunogenicity of hapten

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  • ?. Tolerogen and allergen
  • Tolerogen substances to induce specific
    tolerance.
  • Allergen substances to induce hypersensitivity
    (type I)

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Part ? Factors affecting immunogenicity
  • ?. Factors related to antigens
  • ?. Factors related to host
  • ?. Methods of immunization  

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?. Factors related to antigens  
  • Foreignness
  • According to Burnet, foreignness means substances
    which never contact with embryonic lymphocytes.

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?. Factors related to antigens  
  • 1. Foreignness Non-selfsubstances and self
    components
  • Xeno-substances various pathogens and their
    products, xeno-protein, etc.
  • Allo-substances ABO blood type, HLA, etc.
  • Self components
  • - release of sequester antigen
  • - degeneration

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2. Physical and chemical properties
  • (1) Molecular weight
  • reasonable large molecule( gt10.0 kd)
  • more stationary
  • more surface structure for lymphocyte to recognize

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  • (2) Chemical composition and structure
  • Proteins gtPolysaccharides gtNucleic Acids gtLipids
  • aromatic ring
  • ring gt linear
  • (3) Physical nature
  • Polymer gt monomer
  • Particulate gt Soluble

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?. Factors related to host
  • 1. Genetic background (Species, Individual)
  • 2. Age, sex and healthy status

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?. Pathway of immunization
  • 1. Dosage of antigen
  • 2. Times of injection
  • 3. Ways
  • Intracutaneousgtsubcutaneousgtmusclegtintravenousgtora
    l
  • 4. Adjuvant
  • Certain substances which can enhance the Ir or
    change the type of Ir

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  • What measures can be taken to increase the titers
    of antibody when preparing antibodies against
    sheep red blood cells in mice? Why?

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Part ?. Specificity and cross reaction of
antigen
  • Specificity
  • Exist in both immunogenecity and immunoreactivity
  • The basis of immunologic diagnosis and
    immunologic therapy

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?. Antigenic determinant
  • 1. Antigen determinants (epitope) are small
    particular chemical groups existing in antigen
    which combine with TCR/BCR or Ab.
  • Polypeptide antigen----5-23 amino acid
    residues
  • Polysaccharide antigen----5-7 monosaccharides
  • Nuclear acid antigen----6-8 nucleotide

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  • 2. Antigenic valence Total number of
    determinants which can be bound by antibody or
    antigenic receptor of lymphocytes.
  • Most natural antigens are polyvalence antigen.
  • Hapten is monovalence antigen.

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?. Classification of antigenic determinant
  • 1. According to the site and structure of Ag
    determinants
  • Conformational determinants
  • Sequential (or linear) determinants

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Conformational determinants
  • Conformational determinants are formed by amino
    acid residues that arent in a sequence but
    become spatially juxtaposed in the folded
    protein.
  • They are normally exist on the surface of antigen
    molecules.
  • They are recognized by B cells or antibody.

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Sequential (or linear) determinants
  • Epitopes formed by several adjacent amino acid
    residues are called linear determinants.
  • They are exist on the surface of antigen
    molecules or inside molecules.
  • They are mainly recognized by T cells, but some
    also can be recognized by B cells.

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B
T/B
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  • 2. According to types of cells recognizing
    antigenic determinants
  • T cell determinants (T cell epitopes) TCR
  • B cell determinants (B cell epitopes) BCR
  • Functional determinants
  • Hidden determinants

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T cell epitope
  • Antigenic determinants recognized by T cells
    (TCR)
  • Composition
  • Peptides
  • Sequential determinants(Exist in anywhere of Ag)
  • Processed (APC)
  • MHC presentation
  • Size
  • 8-23 residues

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B cell epitope
  • Antigenic determinants Recognized by B
    cells(BCR)and Ab
  • Composition
  • Peptide, polysaccharides, nucleic acids
  • Conformational determinants or Sequential
    determinants (existed on the surface of Ag)
  • Recognized directly
  • No APC and MHC
  • Size
  • 5-15 residues

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B
B/T
??
??
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Comparison T cell epitope and B cell epitope

  • T cell epitope
    B cell epitope
  • Structure linear epitope
    conformational epitope

  • or linear epitope
  • Receptor TCR
    BCR
  • Features proteins
    proteins, polysaccharides
  • Size 5-23 amino acid residues
    5-15 amino acid residues

  • or 5-7 monosaccharides

  • or 5-8 nucleotides
  • Location any part of antigen
    mostly exist on the surface of

  • antigen
  • MHC molecules yes
    no
  • APC yes
    no

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  • Functional determinant epitope existed on the
    surface of Ag which can be recognized by BCR or
    combined with Ab easily.
  • Immunodominant epitopes specially important
    determinant.
  • Hidden determinant epitope existed inside of Ag
    which can not be recognized by BCR or combined
    with Ab easily.

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?. Common antigen and cross reaction
  • Commom antigen different Ag own the same epitope
    or their epitope have similar structure, these
    epitopes are called common antigen.
  • Species antigen
  • Heterophilic antigen common antigen among human,
    animal or microbes.

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  • Cross reaction reaction between the same Ab and
    different Ag with same similar determinants.

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  • Mechanism of cross reaction
  • ---common Ag determinant.
  • ---similar structure of Ag determinant.
  • Significance
  • ---Because there are some common antigen
    determinants between different microbes, so the
    antiserum against one kind of Ag can also react
    with another Ag and cause a cross reaction.
  • ---In clinic, existence of cross reaction may
    lead to wrong diagnosis.

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Part ?. Classification of Ag
  • ?. According to immunogenicity of Ag
  • ?. According to dependence of T cells
  • ?. According to source of Ag
  • ?. Others

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  • ?. According to immunogenicity of Ag
  • ----Complete Ag
  • ----Hapten

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?. According to dependence of T cells
  • 1. TD-Ag (thymus dependent Ag ) TD-Ag can
    stimulate B cells to produce Ab only with
  • the help of T cells.
  • Most TD-Ags are protein
  • More kinds of determinant, each kind with less
    number
  • Induce HI and CMI
  • Stimulate B cell to produce IgG, IgM, IgA
  • Immune memory

41
  • 2. TI-Ag (thymus independent Ag) stimulate B
    cells to produce Ab without the help of T cell.
  • Most are polysaccharide
  • There is more same repeat determinant
  • Can not induce CMI
  • Only induce B cell to produce IgM
  • No memory

42
Comparison of TD-Ag and TI-Ag
TD-Ag TI-Ag
Component Protein, more kinds Polysaccharide, repeat epitope
Help of T cell Yes No
Immune reponse HI and CMI HI
Type of Ab more,IgG IgM
Affinity of Ab High Low
Immune memory Yes No
43
  • ?. According to source of Ag
  • Xenoantigen
  • Alloantigen
  • Autoantigen
  • Heterophilic Ag

44
?. Others
  • l  Chemical component
  • protein gtpolysacchride gt nucleic acid gtlipid
  • l   Natural Ag and artificial Ag

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Part ?. Important Ags in medicine
  • ?. Heterogenous Ag (xeno-antigen)
  • 1. Pathogens Surface antigen Vi Ag
  • Somatic Ag O Ag
  • Flagellar Ag H Ag

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  • 2. Exotoxin and toxoid
  • Exotoxin Produced by G bacteria,
  • Strong immunogenicity and pathogenicity.     
  • Toxoid Under suitable conditions, exotoxin loss
    its toxicity without affecting its
    immunogenicity, then the exotoxin turned into
    toxoid.
  • Anti-toxin

48
  • ?. Immune serum animal serum contains Abs after
    immunized by some Ag
  • Neutralize exotoxins
  • Serum disease

49
  • ?. Heterophilic Ag (forssman Ag)
  • -Common Ags are shared by different species
  • -No specificity of species
  • - Significance immunopathology
  • Diagnosis

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?. Alloantigen
  • 1. Antigen of red blood cell (blood typing)
  • ABO system
  • -very important in transfusion
  • Rh system (in Chinese gt99RH)
  • -heamolytic disease of the newborn
  • 2. Human leukocyte antigen, HLA system
  • -relate to transplantation
  • -very important in immune regulation

51
?. Autoantigen
  • 1. Release of sequestered Ag
  • 2. Modified of protein

52
?. Tumor antigen
  •  Tumor specific Ag (TSA)
  • --Only express on the tumor cells but normal
    cells
  •  Tumor associated Ag (TAA)
  • --Its express is high on tumor cells but low
    on normal cells, eg. AFP CEA

53
Part ?. Superantigen and adjuvant
  • ?. Superantigen (SAg) Antigens that can
    non-specifically stimulate a plenty of T/B cells
    and induce a very strong Ir with a extremely low
    concentration.

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The mechanism of SAg is different from that of
Ags or mitogen.
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The mechanism of SAg is different from that of
Ags or mitogen.
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  • T cell SAg exotoxin, protein of reverse
    transcript virus
  • B cell SAg SPA(staphylococcal protein A)
    HIVgp120

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  • ?. Adjuvant
  • ----Adjuvant is certain substance which can
    enhance the Ir or change the type of Ir when it
    is injected before or together with the antigens.

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  • Classification of adjuvant
  • Organic adjuvants BCG
  • Inorganic adjuvants Al(OH)3
  • Synthesized adjuvants polyIC
  • New adjuvants nanomes, CpG,etc
  • Common adjuvant
  • Incomplete Freunds adjuvant (IFA)
  • Complete Freunds adjuvant (CFA)

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  • Mechanisms of adjuvant
  • Change the chemical and physical characters of Ag
  • Improves the Ag process and presentation ability
    of macrophages
  • Stimulates proliferation of lymphocytes

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What you should know by the end of this lecture?
  • Definition and characteristics of antigen
  • Definition of antigenic determinants,conformationa
    l determinants and linear determinants
  • Difference between T cell epitopes and B cell
    epitopes
  • Definition of common antigen and cross reaction
  • Difference between TD-Ag and TI-Ag
  • How can you classify different Ag?
  • what is TSA,TAA, hetreophilic Ag?
  • Important antigens in medicine
  • Adjuvant
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