Antigen Structure and Immunogenicity

1. AntigenStructure and Immunogenicity Folder Title: Antigens(With TP Slides) Updated: September 17, 2013

2. Antigen Recognition by the Specific Immune System:Recognition by B-cell and T-cell Receptors Antigen (Ag): Binds specifically to an antibody binding site (Ab), or to a T-cell receptor (TCR) Immunogen: Binds specifically to an antibody binding site or to a T-cell receptor, and generates a humoral or cellular immune response. All immunogens must be antigens, Not all antigens can generate a response.

3. Haptens and Epitopes Haptens: Small organic molecule (e.g. 1-Fluoro-2,4-dinitrobenzene) Not Immunogenic by themselves Can be immunogenic when attached to an immunogenic macromolecular carrier The Anti-hapten antibody so generated will bind the Hapten Epitope: A region of a macromolecular antigen that is actually an antigenic determinant, a molecular sub-region that is actually recognized and bound by an Antibody or T-Cell Receptor

4. Antigen-Antibody Complementarity Antibody Light Chain Variable Region Fig.4-6bKuby3rd Ed AgAb Sep Antibody Heavy ChainVariable Region Influenza Virus Antigen

5. Antigen - Antibody Binding Antibody Light Chain Variable Region Fig. 4-6a Kuby 3rd Ed AgAb Kiss Antibody Heavy Chain Variable Region Influenza Virus Antigen

6. Prot2nd

8. Primary sequential epitopes in sperm whale myoglobin

9. Conformational (non-sequential) Epitope in Hen Egg White Lysozyme. (Colors show amino acid side chains contacting the two different chains of the antibody, or contacting both chains. Antibody structure to be covered later)

10. What Determines Immunogenicity of an Antigen? • Properties of the immunogen(See detailed breakdown next slide) • Properties of the Host (Slides 12 and 18) • a. Genetic • b. Physiological • 3. Mode of Antigen Exposure

11. ImGenFx1

12. ImGenFx2

13. Ag&MHCa

14. Ag&MHCb

15. Ag&MHCc

16. Ag&MHCd

17. Ag&MHC

18. ImGenFx3

19. ImAdmin

20. Conformational Properties of Epitopes for Antibodies

21. 64 80

22. Hen Egg-White Lysozyme: Conformations of Sequence 62 to 80

24. Anti-hapten Antibodies

25. See Figure 4-1 p. 77 Kuby, 6th Edition AbHapten

27. “Fill-in-the Blank” Question:When a small organic molecule is made immunogenic by attaching it to a macromolecule it is called a__ __ __ __ __ __

28. What is this molecular model showing?

29. Immunogenicity of Antigens is Controlled by the Nature of the Antigen, the Genetics of the Host, and the Mode of Immunogen Exposure. Give an example of what is meant by “Mode of Immunogen or Antigen Exposure”

30. AgByB&Ta

31. AgByB&Tb

32. AgByB&T

33. Conformational (non-sequential) Epitope in Hen Egg White Lysozyme.

34. Antigens in Immunologically-BasedClinical Diagnosis and Pathology Cancer Antigens in Diagnosis of Cancer Carcino-Embryonic Antigen (CEA) Prostate Specific Antigen (PSA) Ovarian Cancer Antigen (CA 125) Whole-body Imaging of Metastatic Colon Carcinoma A33 Antigen Anti-Human Chorionic Gonadotropin Pregnancy Test(Early Home Pregnancy Test) Type II Allergic Hypersensitivity Blood Group Antigens in Transfusions Hemolytic Disease of New-Borns: Rh Antigen incompatibility Super-Antigens in Toxic Shock Syndrome Med&Ags

35. Antigens in Immunologically-BasedTreatment of Cancers and Other Pathologies:(Specifics Later) Cancer Antigens as Targets for Therapy Radioactively-labeled Antibodies Cytolytic Antibodies Specifically Activated Antigen-presenting Cells.

36. Imaging with Antibodies Carrying “Reporter Groups” Radioactive Isotopes Fluorescent Groups (“Chromophores”) Metals Antigen-Antibody Interactions in Research and Clinical Medicine e.g. Radioactively labeled monoclonal antibody reacting with tumor cell antigens in detection of metastatic colon cancer

37. Imaging on Metastatic Colon Carcinoma with Radioactive-Iodine-Labelled Monoclonal Ab to A33 AgLloyd Old, Scientific American, August, 1996, p. 138) SeeMets Arm Head

38. Antihapten Antibodies in the Detection and Measurement of Small Molecules For example: Anti-HCG (Human chorionic gonadotrophin) antibody in the detection of soluble HCG in urine

39. What will happen when concentration of Anti-HCG-Ab is about equal to Hapten-carrier conjugate? AntiHCG What will happen when you put excess soluble hapten in the way of the anti-HCG-Ab?

40. PregTest

41. Antibodies in Blood Transfusions Antibodies to A, B, O Blood Group Antigens Pre-existing Antibodies to Non-tolerated (Unmatched) Blood Group Antigens : “Isohemagglutinins”

42. ABOTypes

43. ABOAb See Figure 15-13 (b), p. 389, Kuby, 6th Edition

44. ABOSugar Not a hexasaccharide (No terminal sugar) See Figure 15-13 (a), p. 389, Kuby, 6th Edition Galactose

45. Antibodies in Hemolytic Disease of the New-born (HNDB)(Rh-Factor Sensitization) Rh-Factor positive baby – Rh Negative Mother

46. HDNB See Figure 15-14 p. 390, Kuby 6th Edition

47. HDNBPhoto

48. AntiRhAb

49. Following are three Turning Point short answer questions. Please put all notes on the floor. Do not have any electronic devices other than your NXT transmitter. No consulting with other students. If you have a problem with your device, I can provide you with a loaner NXT device. If you have a problem using your NXT device, please ask Elisabeth for help. It is imperative that the integrity of these in-class Turning Point quizzes be maintained at the same level as we will do with the three written exams.

50. “Fill-in-the Blank” Question:Hemolytic disease of the new-born is caused by maternal __ __ __ __ __ __ __ __ __ __attacking the fetus in utero.