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Immunogen

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Title: Immunogen


1
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.

2
  • Antigen non-self substances which can combine
    with TCR or BCR or Ab and have the potential of
    inducing immune response .
  • Antigen
  • Tolerogen
  • Allergen

3
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.

4
  • 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

5
  • 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)

6
  • 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.

7
  • 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.

8
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.

9
  • 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)

10
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
11
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

12
B
B/T
active
degradation
13
  • 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.

14
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

15
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

16
  • 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)

17
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
18
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.
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