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Antigen Structure and Immunogenicity

Understand the recognition and immunogenic properties of antigens, haptens, and epitopes. Explore antibody-antigen interactions, immunogen properties, and antigenic determinants. Learn about antigen-antibody complementarity, immune system response determinants, and clinical applications of antigens in cancer diagnosis and treatment.

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Antigen Structure and Immunogenicity

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  1. AntigenStructure and Immunogenicity Folder Title: AntigensNoTP(Without 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

  7. Primary sequential epitopes in sperm whale myoglobin

  8. 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)

  9. 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

  10. ImGenFx1

  11. ImGenFx2

  12. Ag&MHCa

  13. Ag&MHCb

  14. Ag&MHCc

  15. Ag&MHCd

  16. Ag&MHC

  17. ImGenFx3

  18. ImAdmin

  19. Conformational Properties of Epitopes for Antibodies

  20. 64 80

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

  22. Anti-hapten Antibodies

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

  24. AgByB&Ta

  25. AgByB&Tb

  26. AgByB&T

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

  28. 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

  29. 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.

  30. 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

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

  32. 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

  33. 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?

  34. PregTest

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

  36. ABOTypes

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

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

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

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

  41. HDNBPhoto

  42. AntiRhAb

  43. 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.

  44. Immunopathology of Bacterial Septic Shock Caused by Gram Negative Bacterial Endotoxins: Examples - E. coli Pseudomonas aeruginosa Neisseria meningitidis Meningococcus 70,000 Deaths per year Diarrhea, Fever, Blood Clotting, Blood Pressure Drop Macrophage Activation by Endotoxin: Generates systemic cytokine production - IL1 and TNF-alpha (Tumor necrosis factor) SepticShock

  45. Immunopathology of Bacterial Toxic Shock Exotoxins Secreted or Present Membrane Bound: Act as "Superantigens" Examples - Staphylococcus aureus: TSST1 (Toxic Shock Syndrome Toxin) Streptococcus pyrogenes - Rheumatic fever and shock Staphylococcus enterotoxins: Food poisoning Superantigens cross-link TCR with Antigen-presenting Cell MHC Class II Proteins Generates systemic cytokine production - IL1 and TNF-alpha (Tumor necrosis factor) ToxicShock

  46. SuperAg Staphylococcal enterotoxins (food poisoning) Streptococcal pyrogenes exotoxins (rheumatic fever, toxic shock) See Table 11-2, p. 367 See Figure 11-6 7th Edition p. 367

  47. Mitogens and Lectins Mitogens: Stimulate mitosis and cell division non-specifically(non-specific therefore stimulate polyclonally) Lectins: Proteins that bind to carbohydrate in glycoproteins(Can be potent mitogens) Glycoproteins: Conjugated protein with covalently attached carbohydrate residues

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