Title: Chapter 4 Antigen(Ag)
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2Contents
- Part? Introduction
- Part? Factors Affecting Immunogenicity
- Part? Specificity and Cross-Reaction of Antigens
- Part? Classification of Antigens
- Part? Important Antigens in Medicine
- Part? Superantigen and Adjuvants
3Part? Introduction
- ?. 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.
4- B cells Antibody
- Ag
- T cells Effector T
cells
5Key points
- Stimulate immune system to produce a specific
immune response. - React specifically with the products of the
immune response in vitro or in vivo.
6- ?. 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.
7 1.Immunogenicity to induce the specific immune
response.
T
T
Ag
B
82. Immunoreactivity to combine with
corresponding Ab or sensitized T lymphocyte
9- ?. Complete antigen and hapten
- 1. Complete antigen
- Both Immunogenicity and Immunoreactivity.
-
- 2. Hapten
- Only Immunoreactivity.
- Haptencarrier complete antigen
- Carrier enhance the immunogenicity of hapten
10- ?. Tolerogen and allergen
- Tolerogen substances to induce specific
tolerance. - Allergen substances to induce hypersensitivity
(type I)
11Part ? Factors affecting immunogenicity
- ?. Factors related to antigens
- ?. Factors related to host
- ?. Methods of immunization
12?. Factors related to antigens
- Foreignness
- According to Burnet, foreignness means substances
which never contact with embryonic lymphocytes.
13?. Factors related to antigens
- 1. Foreignness Non-selfsubstances and self
components - Xeno-substances various pathogens and their
products, xeno-protein, etc. - Allo-substances ABO blood type, HLA, etc.
- Self components
- - release of sequester antigen
- - degeneration
142. Physical and chemical properties
- (1) Molecular weight
- reasonable large molecule( gt10.0 kd)
- more stationary
- more surface structure for lymphocyte to recognize
15 - (2) Chemical composition and structure
- Proteins gtPolysaccharides gtNucleic Acids gtLipids
- aromatic ring
- ring gt linear
- (3) Physical nature
- Polymer gt monomer
- Particulate gt Soluble
-
16?. Factors related to host
- 1. Genetic background (Species, Individual)
- 2. Age, sex and healthy status
17?. Pathway of immunization
- 1. Dosage of antigen
- 2. Times of injection
- 3. Ways
- Intracutaneousgtsubcutaneousgtmusclegtintravenousgtora
l - 4. Adjuvant
- Certain substances which can enhance the Ir or
change the type of Ir
18- What measures can be taken to increase the titers
of antibody when preparing antibodies against
sheep red blood cells in mice? Why?
19Part ?. Specificity and cross reaction of
antigen
- Specificity
- Exist in both immunogenecity and immunoreactivity
- The basis of immunologic diagnosis and
immunologic therapy
20?. 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
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23- 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.
24?. Classification of antigenic determinant
- 1. According to the site and structure of Ag
determinants -
- Conformational determinants
- Sequential (or linear) determinants
-
25Conformational 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.
26Sequential (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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28B
T/B
29- 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
-
30T 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
31B 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
32B
B/T
??
??
33Comparison T cell epitope and B cell epitope
-
T cell epitope
B cell epitope - Structure linear 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 yes
no
34- 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.
35?. 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.
36- Cross reaction reaction between the same Ab and
different Ag with same similar determinants.
37- 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.
38Part ?. Classification of Ag
- ?. According to immunogenicity of Ag
- ?. According to dependence of T cells
- ?. According to source of Ag
- ?. Others
39- ?. According to immunogenicity of Ag
- ----Complete Ag
- ----Hapten
40 ?. 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
41- 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
42Comparison of TD-Ag and TI-Ag
TD-Ag TI-Ag
Component Protein, more kinds Polysaccharide, repeat epitope
Help of T cell Yes No
Immune reponse HI and CMI HI
Type of Ab more,IgG IgM
Affinity of Ab High Low
Immune memory Yes No
43- ?. According to source of Ag
- Xenoantigen
- Alloantigen
- Autoantigen
- Heterophilic Ag
44?. Others
- l Chemical component
- protein gtpolysacchride gt nucleic acid gtlipid
- l Natural Ag and artificial Ag
45Part ?. Important Ags in medicine
- ?. Heterogenous Ag (xeno-antigen)
- 1. Pathogens Surface antigen Vi Ag
- Somatic Ag O Ag
- Flagellar Ag H Ag
-
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47- 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
48- ?. Immune serum animal serum contains Abs after
immunized by some Ag - Neutralize exotoxins
- Serum disease
49- ?. Heterophilic Ag (forssman Ag)
- -Common Ags are shared by different species
- -No specificity of species
- - Significance immunopathology
- Diagnosis
50 ?. Alloantigen
- 1. Antigen of red blood cell (blood typing)
- ABO system
- -very important in transfusion
- Rh system (in Chinese gt99RH)
- -heamolytic disease of the newborn
- 2. Human leukocyte antigen, HLA system
- -relate to transplantation
- -very important in immune regulation
51?. Autoantigen
- 1. Release of sequestered Ag
- 2. Modified of protein
52?. 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
53Part ?. Superantigen and adjuvant
- ?. 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. -
54The mechanism of SAg is different from that of
Ags or mitogen.
55The mechanism of SAg is different from that of
Ags or mitogen.
56- T cell SAg exotoxin, protein of reverse
transcript virus - B cell SAg SPA(staphylococcal protein A)
HIVgp120
57- ?. 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. -
58- Classification of adjuvant
- Organic adjuvants BCG
- Inorganic adjuvants Al(OH)3
- Synthesized adjuvants polyIC
- New adjuvants nanomes, CpG,etc
- Common adjuvant
- Incomplete Freunds adjuvant (IFA)
- Complete Freunds adjuvant (CFA)
59- Mechanisms of adjuvant
- Change the chemical and physical characters of Ag
- Improves the Ag process and presentation ability
of macrophages - Stimulates proliferation of lymphocytes
60What 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?
- Important antigens in medicine
- Adjuvant