Immunogen

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Definitions

• Immunogen
• Antigen (Ag)
• Immunogenicity
• An ability of antigen which can stimulate the
  body to evoke a specific immune response (Ab or
  effect T cells).
•  
• Antigenicity (Immunoreactivity)
• An ability of antigen which can combine with
  corresponding Ab or
  sensitized T lymphocyte.

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• Antigen non-self substances which can combine
  with TCR or BCR or Ab and have the potential of
  inducing immune response .
• Antigen
• Tolerogen
• Allergen

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Factors Influencing ImmunogenicityContribution
of the Immunogen

• Foreignness
• 1. Non-self substances
• 2. self component
• degeneration release of sequester antigen, eg,
  sperm, brain tissue, et al.
• According to Burnnet, Foreignness means
  substances which never contact with embronic
  lymphocytes.

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• Foreignness
• Size (Molecule weight)
• reasonable large molecule( gt10.0 kd) has good
  immuogenecity.
• - more stationary
• - more surface structure for lymphocyte to
  recognize
• hapten and carrier
• hapten
• substances which can combine with Ab, but
  cannot induce immune response independently. In
  another word, hapten only possess
  immunoreactivity.
• carrier
• enhance the immunogenicity of hapten complete
  antigen
• Hapten Carrier complete antigen

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• Chemical nature Complexity
• - ring gt linear
• - ProteinsgtPolysaccharides gtNucleic Acids gtLipids
• Some glycolipids and phosopholipids can be
  immunogenic for T cells and illicit a
  cell mediated immune response.
• Physical Form
• Particulate gt Soluble
• Polymer gt Monomer
• Denatured gt Native
• Degradability
• More deradability More
  immunogenicity
• Ag processing by Ag Presenting Cells (APC)

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• Genetics
• Species
• Responders vs Non-responders
• MHC molecules
• Individual
• Age, health, etc.
• Dose Times
• Route
• Subcutaneous gt Intravenous gt Intragastric
• Adjuvant
• Substances that enhance an immune response to an
  Ag or change the type of immune response when it
  is injected before or together with the antigens.
  

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• Classification of adjuvants
• - biological adjuvant BCG, LPS
• - synthesized adjuvant Incomplete Freunds
  adjuvant,
• complete
  Freunds adjuvant
• - chemical adjuvant Aluminium Salts
• Mechanisms of adjuvants
• - change the chemical and physical charactes of
  Ag like halflife increase.
• - improves the Ag process and presentation
  ability of macrophages.
• - stimulates proliferation of lymphocytes via
  induction of costimulatory molecules.
• - increase in inflammation responses.

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Antigenic determinant

• Antigen determiants (epitope)
• - are small particular chemical groups of
  antigen which decide the specificity of the
  antigen. It is actually the combining site of Ag
  and Ab.
• - a subtle change of antigenic determinant
  (characteristics, number and conformation) can
  influence the specificity of Ag.
• Antigenic valence
• total number of determinant which can be combined
  with Ab.

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• Commom antigen Cross reaction
• - different Ag own the same epitope or their
  epitope have similar structure,these epitopes are
  called common antigen.
• - reaction between the same Ab and different Ag
  with same similar determiants.
• mechanism of cross reaction
• --- common Ag determinant (toxin toxoid)
• --- similar structure of Ag determinant (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)

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Cross-reactive recognition for alloreactivityDiff
erences in MHC molecule expression between a
donor and a recipient are said to be allogenic,
provoking alloreactions that cause graft
rejection..
Immune response to foreign antigens
Acute response to the graft expressing allogeneic
MHC
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Classification of Antigenic determinant

• 1. Sequential Conformational determinant
• Sequential (or linear ) determinant
• --- determinants composed of continuous residues
• --- primary Structure
• --- exist in any where of Ag
• --- recognized by T cell or B cell
• Conformational determinant
• --- determinants composed of discontinuous
  residues by conformation
• --- secondary, tertiary quarternary Structures
• --- exist on the surface of Ag
  
• --- recognized by B cell

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B
B/T
active
degradation
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• 2. Functional Sequester determinants
• Functional determinate or Immunodominant groups
  (IDG) epitope existed on the surface of Ag which
  can be recognized by BCR or combined with Ab
  easily.
• Sequester determinant
• epitope existed inside of Ag which can not be
  recognized by BCR or combined with Ab easily.

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3. B cell epitopes and T cell epitopes

• B cell epitope
• - 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 (No MHC)
• - Size 5-7 residues
• T cell epitope
• - Antigenic Determinants recognized by T
  cells(TCR)
• - CompositionPeptides
• - Sequential determinants (Exist in anywhere of
  Ag)
• - Recognized indirectly (Processed and MHC
  presentated)
• - Size 8 -17 residues

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Classification of Antigens
1. T-independent T-dependent Antigens

• T-independent
• - Polysaccharides Pneumococcal polysaccharide,
  lipopolysaccharide, Flagella

• - Polymeric structure
• - Polyclonal B cell activation
• Yes -Type 1 (TI-1)
• No - Type 2 (TI-2)
• - Resistance to degradation
• T-dependent
• - Proteinsmicrobial, non-self or altered-self
  proteins

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• 2. According to relative xenogenic, allogenic,
  autogenic antigen
• Xenogenic antigen
• Ags comes from another species Microbial Ag
• Allogenic antigen
• Ags comes from different individuals of the same
  species
• - antigen of red blood cell (ABO system, Rh
  system)
• - Human leukocyte antigen, HLA system
• Autogenic antigen
• Ags comes from self body
• - Release of sequestered Ag
• - Degeneration of protein
• - Tumor antigen
• Heterophile Ag (forssman Ag)
• common Ags are shared by different species (no
  specificity of species)

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3. Superantigen

• Antigens that can non-specifically stimulate a
  plenty of T/B cells and induce a very strong
  Immune respose with a extremely low concentration
  
• Staphylococcalenterotoxins, Streptococcal
  pyrogenic exotoxins, staphylococcal protein A,
  HIVgp120

Monoclonal/Oligoclonal T cell response. 1104 -
1105
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4. Mitogens

• Mitogens are agents that are able to induce cell
  division (mitosis)  in a high percentage of T or
  B cells. This proliferation is described as
  polyclonal activation (as opposed to clonal
  expansion following the specific encounter with a
  conventional immunogen). There are T cell
  mitogens and B cell mitogens.
• A number of common mitogens are lectins. Lectins
  are proteins which bind to specific carbohydrate
  groups (moieties). They bind to glycoproteins on
  the surface of the lymphocytes and cause
  activation. But they do not act via conventional
  TcR-epitope or  Ig-epitope interactions. Lectin
  Examples Con A PHA (T cell mitogen), PWM (T
  and B cell mitogen)
• Another important mitogen which is NOT a lectin
  is LPS (lipopolysaccharide). This polysaccharide
  component of the outer membrane of gram negative
  bacteria is also known as endotoxin.
• LPS is a very potent mitogen for B cells.