Chapter 4 Antigen(Ag)

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• 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

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  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

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• 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

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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
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• ?. According to source of Ag
• Xenoantigen
• Alloantigen
• Autoantigen
• Heterophilic Ag

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?. 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

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

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• ?. 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

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?. Autoantigen

• 1. Release of sequestered Ag
• 2. Modified of protein

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?. 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

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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