antigen immunology chen weilin, ph.d institute of immunology, zju

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)