Transcript Chapter 13 Antigen - Shandong University

Chapter 4 Antigen(Ag）
1
Contents
PartⅠ Introduction
PartⅡ Factors Affecting Immunogenicity
PartⅢ Specificity and Cross-Reaction of Antigens
PartⅣ Classification of Antigens
PartⅤ Important Antigens in Medicine
PartⅥ Superantigen and Adjuvants
PartⅠ Introduction
Ⅰ. 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.
B cells
Antibody
T cells
Effector T cells
Ag
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.
Ⅱ. 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.
1.Immunogenicity: to induce the specific immune response.
T
Ag
B
T
2. Immunoreactivity: to combine with
corresponding Ab or sensitized T lymphocyte
T
Ag
B
T
Effector T cell
Ⅲ. Complete antigen and hapten
1. Complete antigen:
Both Immunogenicity and Immunoreactivity.
2. Hapten:
Only Immunoreactivity.
Hapten+carrier complete antigen
Carrier: enhance the immunogenicity of hapten
Ⅳ. Tolerogen and allergen
• Tolerogen: substances to induce specific
tolerance.
• Allergen: substances to induce
hypersensitivity (type I)
Part Ⅱ Factors affecting
immunogenicity
Ⅰ. Factors related to antigens
Ⅱ. Factors related to host
Ⅲ. Methods of immunization
Ⅰ. Factors related to antigens
1. Foreignness
•
According to Burnet, foreignness means
substances which never contact with
embryonic lymphocytes.
Ⅰ. Factors related to antigens
1. Foreignness: “Non-self”substances and
self components
(1) Xeno-substances: various pathogens and
their products, xeno-protein, etc.
(2) Allo-substances: ABO blood type, HLA,
etc.
(3) Self components:
- release of sequester antigen
- degeneration
2. Physical and chemical properties
(1) Molecular weight:
reasonable large molecule( >10.0 kd)
•
•
more stationary
more surface structure for lymphocyte to
recognize
(2) Chemical composition and structure
• Proteins >Polysaccharides >Nucleic Acids >Lipids
aromatic ring
ring > linear
(3) Physical nature
Polymer > monomer
Particulate > Soluble
Ⅱ. Factors related to host
1. Genetic background (Species, Individual)
2. Age, sex and healthy status
Ⅲ. Pathway of immunization
1. Dosage of antigen
2. Times of injection
3. Ways:
Intracutaneous>subcutaneous>muscle>intravenous
>oral
4. Adjuvant:
Certain substances which can enhance the Ir or
change the type of Ir
• What measures can be taken to increase
the titers of antibody when preparing
antibodies against sheep red blood cells in
mice? Why?
Part Ⅲ. Specificity and cross
reaction of antigen
Specificity
• Exist in both immunogenecity and
immunoreactivity
• The basis of immunologic diagnosis and
immunologic therapy
Ⅰ. 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
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.
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.
B
T/B
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
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
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
B
B/T
激活
降解
Comparison T cell epitope and B cell epitope
T cell epitope
Structure
B cell 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
linear epitope
yes
no
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.
Ⅲ. 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.
•Cross reaction: reaction between the same Ab
and different Ag with same similar determinants.
B
A
C
A
A
B
+
+
+
Anti-A serum
Anti-A, B Ab
++
+++
+
Anti-B serum
Anti-A, C Ab
+++
++
• 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.
Part Ⅳ. Classification of Ag
Ⅰ.
Ⅱ.
Ⅲ.
Ⅳ.
According to immunogenicity of Ag
According to dependence of T cells
According to source of Ag
Others
Ⅰ. According to immunogenicity of Ag
----Complete Ag
----Hapten
Ⅱ. 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
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
Comparison of TD-Ag and TI-Ag
TD-Ag
TI-Ag
Component
Help of T cell
Protein,
more kinds
Yes
Polysaccharide,
repeat epitope
No
Immune reponse
HI and CMI
HI
Type of Ab
more，IgG
IgM
Affinity of Ab
High
Low
Immune memory
Yes
No
Ⅲ. According to source of Ag
•
•
•
•
Xenoantigen
Alloantigen
Autoantigen
Heterophilic Ag
Ⅳ. Others
l Chemical component
protein >polysacchride > nucleic acid
>lipid
l Natural Ag and artificial Ag
Part Ⅴ. Important Ags in
medicine
Ⅰ. Heterogenous Ag (xeno-antigen)
1. Pathogens: Surface antigen “Vi” Ag
Somatic Ag “O” Ag
Flagellar Ag “H” Ag
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
Ⅱ. Immune serum: animal serum
contains Abs after immunized by some Ag
• Neutralize exotoxins
• Serum disease
Ⅲ. Heterophilic Ag (forssman Ag)
-Common Ags are shared by different species
-No specificity of species
- 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
2. Human leukocyte antigen, HLA system
-relate to transplantation
-very important in immune regulation
Ⅴ. Autoantigen
1. Release of sequestered Ag
2. Modified of protein
Ⅵ. 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
Part Ⅵ. Superantigen and
adjuvant
Ⅰ. 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.
Conventional Antigen
Superantigen
The mechanism of SAg is different from that of
Ags or mitogen.
The mechanism of SAg is different from that of
Ags or mitogen.
• T cell SAg: exotoxin, protein of reverse
transcript virus
• B cell SAg: SPA(staphylococcal protein
A) HIV:gp120
Ⅱ. 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.
Classification of adjuvant:
Organic adjuvants: BCG
Inorganic adjuvants: Al(OH)3
Synthesized adjuvants: polyI:C
New adjuvants: nanomes, CpG,etc
Common adjuvant:
Incomplete Freund’s adjuvant (IFA)
Complete Freund’s adjuvant (CFA)
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?
 Important antigens in medicine
 Adjuvant