Antigen IMMUNOLOGY Chen Weilin, Ph.D Institute of immunology, ZJU
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Antigen IMMUNOLOGY
Chen Weilin, Ph.DInstitute of immunology, ZJU
Antigen
1. Introduction
2. Antigenicity and specificity
3. Requirements for immunogenicity
4. Types of antigens
5. Superantigen
6. Adjuvant
Introduction1.Antigen (Ag) - the substances that induce a
specific immune response and subsequently react with the products of a specific immune response.
2.Properties of Ag -immunogenicity immunoreactivity3. Immunogen - A substance that induces a
specific immune response.
Antigen
Antigen
Introduction4.Hapten - A substance that is non-immunogenic but
which can react with the products of a specific immune response. Haptens are small molecules which could never induce
an immune response when administered by themselves but which can when coupled to a carrier molecule.
Haptens have the property of antigenicity but not immunogenicity.
5. Tolerogen,allergen
Antigenicity and specificityHapten-carrier effect
Antigen
Antigenicity and specificityⅠ. Foreignness - The immune system normally discriminates
between self and non-self such that only foreign molecules are immunogenic.
Antigenicity and specificityⅡ. specificity 1. Antigenic determinant (epitope) - the portion of the antigen that binds specifically with the binding site of an antibody or a receptor on a lymphocyte. - the size of an epitope is approximately equivalent to 5-7 amino acids.
Antigen
(Karl Landsteiner l868-1943)1930 Nobel Prize
Antigen
Antigenicity and specificitydescription
example
One epitope
haptens
Many epitopes of the same specificity
Many polysaccharides, homopolymers
Many epitopes of different specificity
proteins
Reprensentation of some possible antigenic structures
Antigenicity and specificity
2.structure of epitope conformational
determinant sequential determinant
Antigen
3. Epitopes recognized by B cells Epitopes recognized by T cells
B cell epitope
T cell epitopeDegradati
on
Natural protein
Antigenic peptide
T cell epitope
B cell epitope and T cell epitope
Antigen and vaccine
Antigen
T and B cell epitopes in a protein antigen
Antigenicity and specificity T cell epitope B cell epitopeReceptor TCR BCRMHC necessary non-necessary Character linear short natural polypeptide peptide polysaccharidesSize 8 ～ 12 aa(CD8+T) 5 ～ 15 aa 12 ～ 17aa(CD4+T) 5 ～ 7monosaccharidesType linear determinant conformational determinant ; linear determinant Location everywhere of Ag surface of Ag
Antigen
Antigen
Antigenicity and specificityⅢ .common antigen and cross-reaction
A. Contribution of the Immunogen1. Foreignness - The immune system normally discriminates
between self and non-self such that only foreign molecules are immunogenic.
Factors influencing immunogenicity
Factors influencing immunogenicityA. Contribution of the Immunogen2.Chemical Composition - In general, the more
complex the substance is chemically the more immunogenic it will be.
3. Size - There is not absolute size above which a substance will be immunogenic. In general, the larger the molecule the more immunogenic it is likely to be.
Antigen
Factors influencing immunogenicity
4.Chemical Complexity- an increase in the chemical complexity of a compound is accompanied by an increase in its immunogenicity
5.Conformation and accessibility
6. Physical form - In general particulate antigens are more immunogenic than soluble ones and denatured antigens more immunogenic than the native form.
Antigen
Antigen
Factors influencing immunogenicity
B. Contribution of the Biological System1. Genetic Factors - Some substances are immunogenic in
one species but not in another. Similarly, some substances are immunogenic in one
individual but not in others (i.e.responders and non-responders).
2. Age - Age can also influence immunogenicity. Usually the very young and the very old have a
diminished ability to mount and immune response in response to an immunogen.
Antigen
Factors influencing immunogenicity
Factors influencing immunogenicityC. Method of Administration1. Dose - The dose of administration of an immunogen
can influence its immunogenicity. 2. Route - Generally the subcutaneous route is better
than the intravenous or intragastric routes. The route of antigen administration can also alter the
nature of the response3. Adjuvants
Antigen
Types of antigensTh:Thymus-dependent antigen(TD-Ag)
Thymus-independent antigen(TI-Ag)
Relative:Xenogenic antigen
Allogenic antigen
Autoantigen
Heterophilic antigen
Idiotypic antigen
Antigen
Types of antigensTD-Ag
T-dependent antigens are those that do not directly stimulate the production of antibody without the help of T cells. Proteins are T-dependent antigens.
Antigen
Types of antigensTI-Ag
T-independent antigens are antigens which can directly stimulate the B cells to produce antibody without the requirement for T cell help In general,polysaccharides are T-independent antigens. The responses to these antigens differ from the responses to other antigens.
Antigen
Types of antigensTI-Ag
T-independent antigens can be subdivided
into Type 1 and Type 2 based on their ability to polyclonally activate B cells. Type 1 T independent antigens are polyclonal activators while Type 2 are not.
Antigen
Types of antigensXenogenic Ag
-An antigen found in more than one species.
Antigen
Types of antigensAllogenic Ag
-individuals of a species differ in alleles (are allogeneic) and the antigenic diffences will cause an immune response to allografts.
The antigens concerned are often of the MHC and are referred to as alloantigens.
Antigen
Types of antigensAutoantigen
-The antigens of an organisms own cells and cell products are self antigens to the immune system of that organisn.
- Clones of immune cells reactive with self antigens are normally eliminated.
Antigen
Types of antigensHeterophilic Ag(Forssman antigen)
- A cross-reacting antigen that appears in widely ranging species such as humans and bacteria.
Antigen
Types of antigensidiotypic Ag
- The combined antigenic determinants (idiotopes) found on antibodies of an individual that are directed at a particular antigen; such antigenic determinants are found only in the variable region.
Antigen
antibodyantigen
Antigen may be protein,carbohydrate,etc.
Antigenicdeterminant
Miceimmunizedidiotype1
First antibody selectedfor high affinity forimmunizing antigen,made monoclonal
Anti-idiotype antibodiesRaised against idiotype 1
Second antibodiesscreened for similarityto original antigen
Anti-idiotype 1
Anti-idiotype 1
like antigen unlike antigen
Superantigen (SAg) • When the immune system encounters a
conventional TD-Ag, only a small fraction (1 in 106 -104) of the T cell population is able to recognize the antigen and become activated (monoclonal/oligoclonal response). However, there are some Ags which polyclonally activate some subtypes of the T cells (up to 25%). These Ags are called superantigens. Such as SEA~SEE, Mls (minor lymphocyte stimulating Ag)
Types of SAgs• T cell SAgs: TCR SAgs: HSP TCR SAgs
• B cell SAgs: SPA, gp120 (HIV) bind BCR
Endogenous: Mls
Exogenous: SE, etc.
Adjuvant• It is a substance which, when mixed with an
immunogen, enhances the immune response against the immunogen.
• The use of adjuvants, however, is often hampered by undesirable side effects such as fever and inflammation.
• CFA, IFA, BCG, LPS, CpG, etc.
Mitogen• PHA (phytohemagglutinin, T, human)• ConA (concanavalin A, T, mice)• LPS (lipopolysaccharide, B,mice)• SPA ( staphylococcus protein, B,human)• PWM (pokeweed mitogen, T/B)
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