1. Antigen IMMUNOLOGY Chen Weilin, Ph.D Institute of immunology, ZJU

2. Antigen 1.Introduction 2.Antigenicity and specificity 3.Requirements for immunogenicity 4.Types of antigens 5.Superantigen 6.Adjuvant

3. Introduction 1.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 immunoreactivity 3. Immunogen - A substance that induces a specific immune response. Antigen

4. Introduction 4. 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

5. Antigenicity and specificity Hapten-carrier effect

6. Antigen Antigenicity and specificity Ⅰ. Foreignness - The immune system normally discriminates between self and non-self such that only foreign molecules are immunogenic.

7. Antigenicity and specificity Ⅱ. 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

8. (Karl Landsteiner l868-1943) 1930 Nobel Prize

9. Antigen Antigenicity and specificity descriptionexample One epitopehaptens Many epitopes of the same specificity Many polysaccharides, homopolymers Many epitopes of different specificity proteins Reprensentation of some possible antigenic structures

10. Antigenicity and specificity 2.structure of epitope conformational determinant sequential determinant Antigen

11. 3. Epitopes recognized by B cells Epitopes recognized by T cells B cell epitope T cell epitope Degradation Natural protein Antigenic peptide T cell epitope B cell epitope and T cell epitope Antigen and vaccine

12. Antigen T and B cell epitopes in a protein antigen

13. Antigenicity and specificity T cell epitope B cell epitope Receptor TCR BCR MHC necessary non-necessary Character linear short natural polypeptide peptide polysaccharides Size 8 ～ 12 aa(CD8 + T) 5 ～ 15 aa 12 ～ 17aa(CD4 + T) 5 ～ 7monosaccharides Type linear determinant conformational determinant ; linear determinant Location everywhere of Ag surface of Ag Antigen

14. Antigenicity and specificity Ⅲ.common antigen and cross-reaction

15. A. Contribution of the Immunogen 1. Foreignness - The immune system normally discriminates between self and non-self such that only foreign molecules are immunogenic. Factors influencing immunogenicity

16. A. Contribution of the Immunogen 2.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

17. 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

18. Factors influencing immunogenicity

19. B. Contribution of the Biological System 1. 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

20. C. Method of Administration 1.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 response 3. Adjuvants Antigen

21. Types of antigens Th: Thymus-dependent antigen(TD-Ag) Thymus-independent antigen(TI-Ag) Relative:Xenogenic antigen Allogenic antigen Autoantigen Heterophilic antigen Idiotypic antigen Antigen

22. Types of antigens TD-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

23. Types of antigens TI-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

24. Types of antigens TI-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

25. Types of antigens Xenogenic Ag -An antigen found in more than one species. Antigen

27. Types of antigens Allogenic 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

28. Types of antigens Autoantigen -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

29. Types of antigens Heterophilic Ag(Forssman antigen) - A cross-reacting antigen that appears in widely ranging species such as humans and bacteria. Antigen

30. Types of antigens idiotypic 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

31. antibody antigen Antigen may be protein, carbohydrate, etc. Antigenic determinant Mice immunized idiotype1 First antibody selected for high affinity for immunizing antigen, made monoclonal Anti-idiotype antibodies Raised against idiotype 1 Second antibodies screened for similarity to original antigen Anti- idiotype 1 Anti- idiotype 1 like antigenunlike antigen

32. Superantigen (SAg) When the immune system encounters a conventional TD-Ag, only a small fraction (1 in 10 6 - 10 4 ) 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)

34. Types of SAgs T cell SAgs: TCR  SAgs: HSP TCR  SAgs B cell SAgs: SPA, gp120 (HIV) bind BCR Endogenous: Mls Exogenous: SE, etc.

37. 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.

38. Mitogen PHA (phytohemagglutinin, T, human) ConA (concanavalin A, T, mice) LPS (lipopolysaccharide, B,mice) SPA ( staphylococcus protein, B,human) PWM (pokeweed mitogen, T/B)