ANTIGEN (IMMUNOGEN)

1. ANTIGEN (IMMUNOGEN) Dr Sateesh.K Assoc Professor

2. ANTIGEN (IMMUNOGEN) • Definition: Any substance capable of provoking the immune system to respond by generating an immune reaction specifically directed at the inducing substance. The response may involve humoral or the cellular limb of the immune response or both.

3. Definition: Any substance which, when introduced into the body, stimulates the production of an antibody with which it reacts specifically and in an observable manner.

4. ANTIGEN • Two attributes of Antigenicity - Induction of immune response (Immunogenicity) - Sp. reaction with Ab or sensitized cells (Immune reactivity)

5. Types of Antigens • Based on the ability to perform functions antigens are classified as • Complete Antigen • Incomplete Antigen/Hapten • Complete antigen is able to induce antibody formation and produce a specific and observable reaction with antibody.

6. Hapten (to fasten) • Haptens are substances which are incapable of inducing antibody formation by themselves, but can react specifically with antibodies. • Haptens become immunogenic on combining with a larger molecule carrier. • Types of haptens: Simple & Complex • Simple haptens are monovalent, hence can’t precipitate with antibody • Complex haptens are polyvalent, hence can precipitate with antibody

7. ANTIGEN • Complete Antigen: Any substance that is able to induce antibody formation and produce a specific observable reaction with the antibody so produced. • Hapten (partial antigens): Low molecular substances incapable of inducing antibody formation but can react specifically with antibody. Haptens become immunogen with carrier mol. (Eg; penicillin)

9. CLASSIFICATION OF ANTIGENS Based on origin: Microbial: Fimbrial, somatic, flagellar, capsular Based on Immune response: ‘T’ dependant Antigens • Depend on the help of ‘T’ lymphocytes • Eg; serum precursors, Erythrocytes, Haptens etc. • IgM, IgG IgA IgE are the Abs • Long memory ‘

10. CLASSIFICATION OF ANTIGENS T’ Independent Antigens • Produce Ab without the help of ‘T’ lympho • Eg; Bact.LPS, Pneumococci polysaccharide, Fimbrial and flagellar Ags • IgM is the Ab • Large mol wt-Ag with repeating epitopes • Short memory

12. TERMS COMMONLY USED Epitope: (Antigenic determinant) • Small area on Ag, capable of sensitizing an immunocyte and also reacting with complimentary site on the sp. antibody. Paratope: • Combining area of the Ab molecule corresponding to the epitope (Hyper variable region of Ab mol.)

13. Antigenic determinant • The smallest unit of antigenicity is known as antigenic determinant or epitope • The epitope is a small area on antigen possessing a specific chemical nature, electrical charge and steric configuration, capable of sensitising a immunocyte to produce antibody and reacting with it. • The combining area on the antibody molecule, corresponding to the epitope is called as paratope

14. Determinants of antigenicity • Size • Chemical nature • Susceptibility to tissue enzymes • Foreignness • Specificity

15. Size • Larger molecular weight substances are more antigenic, while smaller molecular weight substances are not antigenic. Larger mol. (Haemocyanin) More antigenic - Mol. < 10,000 Nonantigenic • Low molecular weight substances can be made antigenic by adsorbing them on large inert particles like bentonite and kaolin

16. Chemical nature: • Most naturally occurring antigens are proteins and polysaccharides. Lipids and nucleic acids are less antigenic. - Protein, polysaccharides More antigenic - Lipid, nucleic acid Less antigenic - Structural complexity; protein with more amino acids, polysaccharides with more monosaccharides - Presence of Aromatic amines (Tyrosin)

17. Susceptibility to tissue enzymes: • Only substances which are metabolised and are susceptible to action of tissue enzymes behave as antigens. • Polysterene latex is not antigenic

18. Foreignness • Only nonself (foreign) antigens induce an immune response. Antigenicity of a substance is related to degree of its foreignness • Antigens from related species are less antigenic than those of distant species. - Tolerance to self Ag is conditioned by contact with them during developmental stage - Break down Auto immune disease - Evolutionarily, greater the gap more is the antigenicity.

19. DETERMINANTS OF ANTIGENICITY (CONTD.) • Genetic constitution of host • Epitopes: More the number of epitopes they are more antigenic • Dosage, route and timing of Ag administration Antigenicity can be enhanced by mixing with an adjuvants (Substance which release slowly and maintain the continuous stimulation)

20. Specificity of natural tissue Ag may be of various types. They are Antigenic Specificity Species Specificity II) Iso Specificity III) Auto Specificity IV) Organ Specificity and V) Heterogenetic specificity.

21. ANTIGENIC SPECIFICITY • Basis of Ag specificity is stereo - chemical • Ag specificity is determined by a single chemical group even by a single acid radical • The importance of position (ortho., meta and para) of the antigenic determinant responsible for Ag specificity • Ag specificity is not absolute. Cross reaction, between species may occur.

22. Species specificity: Tissues of all individuals in a single species share a common antigen. Cross reaction may occur to Ag similarity • Tracing evolutionary relationships between species • Identification of species by blood and seminal stains

23. Iso specificity • Iso antigen are found in some but not all the members of the species. • Eg: Blood group Ags, Rh antigens, Histocompatibility antigens (HCA) • Importance: - • Transfusion, Iso-immunization, Homograft rejection • Disputed paternity • Anthropological study • Histocompatibility Ag; Cellular determinants specific for each individual exist in the plasma membrane of the cell.

24. Auto specificity • Self or auto antigens are normally not antigenic • Circumstances where self Ag behave foreign - Sequestrated Ags: Lens protein, spermatozoa etc. - Release into circulation (Infection, Irradiation, by maneuver) etc.

25. Organ specificity • Organs such as brain kidney and lens protein of different species share a common antigen. Such antigens are characteristics of organ are known as organ specific Ags which lead to organ specificity. Eg : Neuroparalytic complication following neural Antirabies (Sheep) vaccine.

26. Hetero specificity • The same or closely related Ags may occur in different biological species, classes and kingdom. (Heterophile antigens) Eg: Forssmann Antigen: Lipid carbohydrate complex widely distributed in human being animals, birds, plants and bacteria. • Ags are used in serological tests unrelated to causative agents (Weil-Felix for typhus fever, Paul-Bunnel in infectious mononucleosis, Cold Agglutination test in Primary atypical pneumonia, VDRL (Cardiolipin) for syphilis.

27. Superantigen • Super antigens are molecules that interact with antigen presenting cells(APC) non-specifically without undergoing endocytic processing. • Interaction of superantigens with MHC classII molecules of APC and the VB domain of T lymphocyte receptor • This activates large number of lymphocytes as compared to conventional antigen processing. • Massive cytokine expression and immunomodulation takes place.Eg: Staphylococcal Toxic shock syndrome toxin,