Transcript Chapter 13 Antigen

Chapter 4 Antigen
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.
Section I
Properties of Antigens and factors affecting
immunogenicity
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.
Ag
B cells
Ab
T cells
effective T cells
Immunoreactivity
Immunogenicity
Hapten and carrier
 Hapten: Only possess immunoreactivity
 Carrier: enhance the immunogenicity of hapten
 Complete antigen :possess both functions

Hapten +carrier ----complete antigen
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 Burnet’s theory.
 Xeno-substances (Various pathogens and their products, xenoprotein, etc.)
 Allo-substances (ABO blood type, HLA, et al)
 Self components
- degeneration
- release of sequester antigen
- forbidden clone rejuvenate
Burnet Clonal selection theory
Various clones
Clone deletion
birth
Clone selection
2. Certain physical and chemical properties
1) Molecular weight:
Reasonable large molecule( >10.0 kd)
• more stabilization

more surface structures for lymphocytes to
recognize
2) chemical composition and structure
Proteins >Polysaccharides >Nucleic Acids >Lipids
aromatic ring
ring > linear
3) physical nature
polymer > monomer
Particulate > Soluble
Denatured > Native
II. Factors related to host
1. Inheritance (Species, Individual)
2. Age,Sex and healthy condition
III) Methods of immunity
1. Dosage of antigen, times of injection
2. Ways (subcutaneous>intravenous>oral)
3. Adjuvant
Certain substance which can enhance the Ir or
change the type of Ir
Section II.
Specificity and cross reaction of antigen
1. Specificity and antigenic determinants
Exist in both immunogenecity and immunoreactivity
The basis of immunologic diagnosis and immunologic
therapy
Specificity of Ag
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
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
苯
胺
氨
甲
基
笨
酸
The chemical component , arrangement and
conformation affect the specificity of antigen
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.
II. Classification of antigenic determinant
1. According to the site and structure of Ag
determinants
Conformational determinants
Sequential (or linear) determinants
Conformational determinants
 Conformational determinants are
formed by amino acid residues that
aren’t 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.
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.
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
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
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
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.
Comparison T cell epitope and B cell epitope
T cell epitope
Structure
linear epitope
B cell 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
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
2
1
2
A
3
Anti-2
Anti-A
B
Anti-2
Anti-B
Anti-1
Anti-3
 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.
Section III. Classification of Ag
I. Classification according to immunogenicity
of the antigens
 Complete Ag
 Hapten
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 MФ
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
2. TI-Ag (thymus independent Ag) :
stimulate B cells to produce Ab without the
help of T cell and MФ
---most are polysaccharide
---there is more same repeat determinants
---only induce B cell to produce IgM
---can not induce CMI
---no memory
TI and TD 抗 原
Antigen
TI-1 抗原
TD-Ag
TI-Ag
CD4
1
2
1
2
CD40/CD40L
B1 细胞
B2 细胞
Th细胞
III according to origin of antigens

xenoantigen

alloantigen

autoantigen
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
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
II. Immune serum of animal :
animal serum contains Abs
 Antibody activation: bind to antigen
 Immunogenicity : hypersensitivity
TAT: Tetanus anti-toxin
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
IV. Alloantigen
1.Antigen of red blood cell (blood typing) :
ABO system
-very important in transfusion
Rh system (in Chinese >99% Rh+)
---heamolytic disease of the newborn(HDNB)
2. Human leukocyte antigen, HLA system
-relate to transplantation
-very important in immune regulation
V. Autoantigen
1. Release of sequestered Ag
2. Modification of protein
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
Section V.
Superantigen and adjuvant
1. Superantigen (SAg) :Substance that can nonspecifically stimulate polyclonal T/B cells and
induce a very strong immune response with a
extremely low concentration
Conventional Antigen
Superantigen
The mechanism of SAg is different from that of Ags.
Superantigen
MHC
TCR
Antigen
 T cell SAg :
enterotoxin
 B cell SAg:
SPA (staphylococcal protein A)
HIV:gp120
Biological actions of superantigen
 1. activate immune response
 2. Immune suppression
 3. induce immune tolerance
Section VI Adjuvants
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 Freund’s adjuvant
complete Freund’s adjuvant
Classification of adjuvant
organic adjuvants: BCG
inorganic adjuvants: Al(OH)3
synthesized adjuvants: polyI:C
complex adjuvants
Mechanisms of adjuvant:
 change the chemical and physical characters
of Ag
 improves the Ag process and presentation
ability of macrophages
 stimulates proliferation of lymphocytes
What you should know by the end of this lecture
 Definition and characteristics of antigen
 Definition of antigenic determinants,conformational
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