Chapter 4 Antigen

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Chapter 4 Antigen
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• Definitions of antigen
• Antigen non-self substances which can
  combine with TCR or BCR or Ab and have the
  potential of inducing immune response .
• Antigen
• Tolerogen an antigen that induces
  immunological tolerance
• Allergen an antigen that elicits an
  immediate hypersensitivity.

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• Section I
• Properties of Antigens and factors affecting
  immunogenicity

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I. Properties of Ag

• Immunogenicity
• An ability of antigen which can stimulate one
  individual to evoke a specific immune response
  (Ab or effector T cells).
•  
• Immunoreactivity (Antigenicity)
• An ability of antigen which can combine
  specifically with corresponding Ab or effector
  T lymphocyte.

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Ag B cells Ab
T cells effective T cells
Immunogenicity
Immunoreactivity
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• Hapten and carrier
• Hapten Only possess immunoreactivity
• Carrier enhance the immunogenicity of hapten
• Complete antigen possess both functions
• Hapten carrier ----complete antigen

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II Factors of influencing immunogenicity

• 1. Factors related to antigens   
• 1)Foreignness
• Non-self substances means substances which
  never contact with embryonic lymphocytes
  according to Burnets theory.
• Xeno-substances (Various pathogens and their
  products, xeno-protein, etc.)
• Allo-substances (ABO blood type, HLA, et al)
• Self components
• - degeneration
• - release of sequester antigen
• - forbidden clone rejuvenate

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Burnet Clonal selection theory
Various clones
Clone deletion
birth
Clone selection
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2. Certain physical and chemical properties

• Molecular weight
• Reasonable large molecule( gt10.0 kd)
•  more stabilization
• more surface structures for lymphocytes 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
• Denatured gt Native

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II. Factors related to host

• 1. Inheritance (Species, Individual)
• 2. Age,Sex and healthy condition

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III) Methods of immunity

• 1. Dosage of antigen, times of injection
• 2. Ways (subcutaneousgtintravenousgtoral)
• 3. Adjuvant
• Certain substance which can enhance the Ir or
  change the type of Ir

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Section II. Specificity and cross reaction of
antigen

• Specificity and antigenic determinants
• Exist in both immunogenecity and
  immunoreactivity
• The basis of immunologic diagnosis and
  immunologic therapy

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Specificity of Ag
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2.Antigenic determinant

• 1)Antigen determinants (epitope) are small
  particular chemical groups existing in antigen
  which can be recognized by TCR/BCR or Ab.
• Polypeptide antigen----5-23 amino acid residues
• Polysaccharide antigen----5-7 monosaccharides
• Nuclear acid antigen----6-8 nucleotides

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• Epitope decide the specificity of the antigen
• a subtle change of antigenic determinant
  (characteristics, number and conformation) can
  influence the specificity of Ag.
• Antigen determinant is the combining site of Ag
  to Ab

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The chemical component , arrangement and
conformation affect the specificity of antigen
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• 2) Antigenic valence
• Total number of determinants which can be bound
  by antibody or antigenic receptor of lymphocytes
  is called antigenic valence.
• Most natural antigens are polyvalence
  antigen.
• Hapen is monovalence antigen.

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II. 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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• 2. According to types of cells recognizing
  antigenic determinants
• T cell determinants(T cell epitopes)
• B cell determinants(B cell epitopes)
• Functional determinants
• Hidden or Sequestered determinants

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T cell determinant

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

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B cell Determinant

• Antigenic Determinants Recognized by B cells and
  Ab
• Composition
• peptide, polysaccharides, nucleic acids
• Sequential determinants or Conformational
  determinants (existed on the surface of Ag)
• Recognized directly by B cells
• No MHC
• Size 5-7 residues

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B cell determinants

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

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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
• Nature proteins
  proteins, polysaccharides
• Size 5-23 amino acid residues
  5-15 amino acid residues
• 
  or 5-7 monosaccharides
• 
  or 5-8 nucleotides
• Position any position in antigen mostly
  exist on the surface of
• 
  antigen
• MHC molecules yes
  no
  
• Presentation

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III. Common antigen and cross reaction

• Common antigen the same or similar determinants
  among various antigens are called common antigen.
• Cross reaction
• The antibodies induced by one kind of antigen
  can react with other antigen because of presence
  of common determinant between two antigens

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2
2
A
1
B
3
Anti-2
Anti-2
Anti-A
Anti-B
Anti-1
Anti-3
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• Mechanism of cross reaction
• ---common Ag determinants
• ---similar structure of Ag determinants
•  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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Section III. Classification of Ag

• I. Classification according to immunogenicity
  
• of the antigens
• Complete Ag
• Hapten

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II. according to whether need the help of T
cells when B cells produce Ab

• 1. TD-Ag (thymus dependent Ag ) TD-Ag can
  stimulate B cells to produce Ab with
• the help of T cells
• 2. TI-Ag (thymus independent Ag) stimulate B
  cells to produce Ab without the help of T cell
  and M?

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• 1. TD-Ag (thymus dependent Ag ) TD-Ag can
  stimulate B cells to produce Ab only with
• the help of T cells
• ---most of TD-Ag are protein
• ----more kinds of determinants, less number of
  each kind
• ---stimulate B cell to produce IgG, IgM, IgA
• ---capable of inducing CMI
• ---immune memory

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• 2. TI-Ag (thymus independent Ag) stimulate B
  cells to produce Ab without the help of T cell
  and M?
• ---most are polysaccharide
• ---there is more same repeat determinants
• ---only induce B cell to produce IgM
• ---can not induce CMI
• ---no memory

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Antigen
TI-Ag
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• III according to origin of antigens
• xenoantigen
• alloantigen
• autoantigen

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Section IV. Important Ags in medicine

• I. Pathogens and their products
• 1.Pathogens Surface antigen Vi Ag
• Somatic Ag O Ag
• Flagellar Ag H Ag
• Pillus Ag  

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• 2. Exotoxin and toxoid
• Exotoxin
• Produced by G bacteria
• Strong immunogenicity and pathogenicity     
• Toxoid
• exotoxin which losses its toxicity and
  maintains its immunogenicity under suitable
  conditions
• Tetanus toxoid

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• II. Immune serum of animal
• animal serum contains Abs
• Antibody activation bind to antigen
• Immunogenicity hypersensitivity
• TAT Tetanus anti-toxin

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• III. Heterophilic Ag (forssman Ag)
• ----common Ags are shared by different
  species
• no specificity of species
• Such as
• Forssman Ag SRBC and guinea pig organs
• Heart or kidney of human and streptococcus
• O14 of E. coli and colonic mucos
• Ox19 of proteus and R. typhi
• -- Significance immunopathology
• Diagnosis

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IV. Alloantigen

• 1.Antigen of red blood cell (blood typing)
• ABO system
• -very important in transfusion
• Rh system (in Chinese gt99 Rh)
• ---heamolytic disease of the newborn(HDNB)
• 2. Human leukocyte antigen, HLA system
• -relate to transplantation
• -very important in immune regulation

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V. Autoantigen

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

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VI. Tumor antigen

•  Tumor specific Ag, TSA
• --only express on the tumor cells but on normal
  cells
•  Tumor associated Ag,TAA
• -- Express highly on tumor cells but lowly on
  normal cells, eg. AFP CEA

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Section V. Superantigen and adjuvant

• 1. Superantigen (SAg) Substance that can
  non-specifically stimulate polyclonal T/B cells
  and induce a very strong immune response with a
  extremely low concentration

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The mechanism of SAg is different from that of
Ags.
Superantigen
MHC
Antigen
TCR
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• T cell SAg
• enterotoxin
• B cell SAg
• SPA (staphylococcal protein A)
• HIVgp120

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Biological actions of superantigen

• 1. activate immune response
• 2. Immune suppression
• 3. induce immune tolerance

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• Section VI Adjuvants

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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
• Common adjuvants
• Incomplete Freunds adjuvant
• complete Freunds adjuvant

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• Classification of adjuvant
• organic adjuvants BCG
• inorganic adjuvants Al(OH)3
• synthesized adjuvants polyIC
• complex adjuvants

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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, superantigen ?
• Important antigens in medicine