Antigens and Immunogens

Transcription

1 Background 1. Medical Importance of Immune System (vaccines, immunodeficiency diseases, hypersensitivity) 2. How the Immune System Works (innate & adaptive immune mech., B/T cells, Abs, Cytokines) 2. Cells and Organs of Immune System

2 Antigens and Immunogens Epitopes, Forces, Specificity, Cross Reactions, Adjuvants Dr. Sudhir Paul

3 Immunogen vs. Antigen Immunogen - Agent capable of binding immune receptors AND inducing an immune response by B cells or T cells Antigen - Agent that binds with varying degrees of specificity to immune receptors (antibodies on B cells; T cell receptor on T cells)

4 Importance of Immunogenicity Germfree colostrum-deprived piglets are immunologically "virgin" and susceptible to microbial infection due to lack of passive maternal immunity. They are, however, immunologically competent as they mount excellent immune response to various immunogens. An immunogen induces specific antibody formation. The initial step in the primary immune response is priming of multipotent uncommitted cells ("virgin" X cells) to committed monopotent cells (Y cells). In the memory response, Y cells proliferate and differentiate into antibody-forming cells (Z cells). Adapted from Y.-B. Kim 1975

5 Importance of Immunogenicity Killed or attenuated microbes; purified proteins, denatured (inactivated) proteins; polysaccharides; DNA vaccines

6 Importance of Immunogenicity Figure 12-8

7 Epitopes Site on antigen surface bound by antibody paratope or T cell receptor. Upper size is 7 x 12 x 35 Angstroms. Usually requires 5-6 high energy attractive contacts, some contacts are repulsive

8 Figure 1-21 Immune receptors

9 Antigen Recognition by B and T Cells Characteristic B cells T cells Mechanism BCR binds Ag TCR binds (Ag + MHC) Antigen nature Protein/polysaccharide/lipid Peptide Epitopes Surface, linear, conformational Internal linear peptides

10 T independent and dependent immune responses Figure 7-6

11 Multi-epitope antigens

12 Figure 3-9

13 Major Immunogen/Antigen Classes Proteins, glycoproteins-most Important Carbohydrates, polysaccharides Lipids Nucleic Acids Miscellaneous-Metals (Ni, Hg), organic chemicals

14 Linear and Conformational Epitopes Linear Epitopes - Short stretches of amino acids (4-7) recognized by Ab when free in solution, Ag is denatured, or native. Only form of T cell epitope. Conformational Epitopes - Require the unaltered, native 3-D shape of Ag for recognition by Ab.

15 Conformational Epitopes

16 Linear T epitope Figure peptide bound 3-23 to MHC molecules class II (important for CD4 cell deficiencies) class I (important for CD8 cell deficiencies)

17 MHC Effects on Immunogenicity Class I-Deficiency can present clinically as a profound CD8 T cell deficiency. Class II-Deficiency can present as chronic infections, low Ig in serum (due to missing CD4+ helper cells), bone marrow transplant indicated.

18 Figure A-2

19 Haptens Low molecular weight. Can bind pre-formed antibodies. Non-immunogenic alone. Coupling to carrier proteins renders it immunogenic.

20 Figure A-3 Rendering haptens immunogenic

21 Haptens in Pediatrics Wyeth makes HibTITER Haemophilus influenza b capsular oliogosaccharide coupled to diphtheria CRM 197 (non-toxic variant). Also make a pneumococcal vaccine PREVNAR with same carrier. Merck makes similar vaccine of H. influenza b coupled to outer membrane protein complex of Neisseria meningitidis serogroup B. The CHO hapten is rendered T-dependent.

22 Immunological Specificity Refers to the ability of immune molecules to distinguish between structurally different antigens. Derives mainly from difference in binding strength Functional roles of polyreactive and monoreactive immune specificities

23 Cross-reactivity Antibody can react with two similar but nonidentical antigens The two may share one or more identical epitopes, e.g., toxoids; diphtheria, tetanus The two may share one or more structurally similar but non-identical epitopes, e.g., bacterial antigens and autoantigens

24 Figure 11-29

25 Adjuvants Substances that are nonimmunogenic alone but enhance the immunogenicity of other molecules by: (a) slow Ag release; (b) inducing Ag aggregation; and (c) stimulating innate immunity via non-bcr, non- TCR receptors

26 Figure A-4

27 Coda Successful immunization depends on HLA haplotype, dose of antigen, route of immunization, use of adjuvant, overall immune status, existing allergies, heterogeneity of antigen mixture, physical state of antigen, stress level of patient. The immune homunculus concept