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Introduction to The Immune Response

Introduction to The Immune Response. Dr. Robert J. Boackle Room 441 BSB, 792-2552 boacklrj@musc.edu http://people.musc.edu/~boacklrj/Syllabus_.htm. The Student should understand the following concepts from this lecture:. The Nature of Antigenic Determinants

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Introduction to The Immune Response

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  1. Introduction to The Immune Response Dr. Robert J. Boackle Room 441 BSB, 792-2552 boacklrj@musc.edu http://people.musc.edu/~boacklrj/Syllabus_.htm

  2. The Student should understand the following concepts from this lecture: • The Nature of Antigenic Determinants • Location of Antigens on Bacterial Cells • After infection, the Filtration of Antigens • Lymphocyte Clones (B Cells and T Cells) • B and T Lymphocyte Clonal Development • B and T Lymphocyte Clonal Proliferation • Lymphocyte Circulation and Trafficking

  3. Non-self Substances Antigens [Ag]

  4. Bacterium Where are antigens located? Lets take a look at the molecular level.

  5. Released Antigens Surface Antigens Bacterial Surface

  6. Released Proteases Surface Antigens Bacterial Surface

  7. Bacterial Proteases play a key role in Periodontal Disease unless they are neutralized by host antibodies

  8. Bacterium Antigens are foreign molecules

  9. Each Antigen (each foreign molecule) (for example a bacterial surface enzyme) has several regions that our body detects as foreign. These areas on the molecule are termed Antigenic Determinants

  10. X EXTERNAL ANTIGENIC DETERMINANTS Activate B Cells EXTERNAL THERE ARE ALSO MANY INTERNAL ANTIGENIC DETERMINANTS (not exposed) Activate T Cells

  11. Antigen Penetration

  12. Antigen Penetration

  13. Antigen Penetration Toll-like Receptors Endotoxin (LPS)

  14. ARTERY VEIN LYMPH NODE AFFERENT LYMPHATIC CAPILLARY EFFERENT LYMPHATIC CAPILLARY

  15. Antigens in the Lymph are filtered in the Lymph Node EFFERENT LYMPHATIC CAPILLARY ARTERY VEIN

  16. Antigen Stimulated Lymph Node Lymphocyte Proliferation Swollen Lymph Nodes ! AL = AFFERENT LYMPHATIC CAPILLARIES AL AL AL AL B CELL RICH AL T CELL RICH EFFERENT ..LYMPHATIC ..CAPILLARY Movement of Lymphocytes from “Blood to Lymph” occurs in the Lymph Nodes Movement of Lymphocytes from “Blood to Lymph” occurs in the Lymph Nodes

  17. Antigens in the Blood are filtered in the Spleen

  18. Lymphocytes are the police force of the Immune System Selectins-Integrins Addressins These Lymphocytes are the detectives and responders They traffic to areas of infection and inflammation! http://people.musc.edu/~boacklrj/integrinLFA-1.pdf

  19. Location of Lymphocytes: Lymph and Lymph Nodes Blood and Spleen Thymus Bone Marrow Lymphoid Tissues Associated with the Mucosa (Tonsils, Gut, Respiratory Tract) Any area after infection

  20. Regulation of the Expression of DNA is the key to the production of different kinds of Lymphocytes And to the understanding of Lymphocyte Clonal Development The ability of a population of Lymphocytes to SPECIFICALLY recognize a foreign antigen

  21. Definitions: 1) One Clone of BLymphocytes is a population of B lymphocytes derived from one original mother B lymphocyte and therefore all members are identical in every way. 2) One Clone of TLymphocytes is a population of T lymphocytes derived from one original mother T lymphocyte and therefore all members are identical in every way.

  22. Definitions: 3) There are thousands of B cell clones and thousands of T cell clones in our body that exist in low numbers until we have an infection. 4) Stem cells are pre-programmed with the DNA-information to generate thousands of different clones of B and T lymphocytes (to bind to thousands of different antigenic determinants). 5) An Antigenic Determinant adheres to the best fitting Clone of B or T Lymphocytes.

  23. B Lymphocyte Clonal Development Clones of B Cells are formed within the Bone Marrow of humans No Antigen Needed! STEM CELLS in the BONE MARROW are pre-programmed with information

  24. Mature B lymphocytes divide very slowly in the absence of antigens BL BL BL

  25. What are the Lymphocyte Receptors for antigenic determinants integrated with the membranes of lymphocytes? For B lymphocytes the Receptors are Antibodies For T lymphocytes the Receptors are T Cell Receptors

  26. IN THE PRESENCE OF ANTIGENS, Clonal Proliferation (B Cell clonal expansion), followed by Differentiation into Plasma cells that produce identical fluid phase antibodies (Ab)

  27. What do we mean by the phrase “Clones of Lymphocytes”

  28. Only those lymphocyte clones that bind in a specific way to antigens are stimulated.

  29. Clones of B and T Lymphocytes (inactive) Clonal Selection Theory

  30. Selected Clones of B Lymphocytes and T Lymphocytes Activate and Proliferate After contacting antigens

  31. Clones of B Lymphocytes become activated by exposed antigenic determinants on antigens Clone B1 Clone B2 CloneB3 And Proliferate Clonal Selection Theory

  32. Proliferation of ONE B Cell Clone after contacting antigen. Clonal Proliferation after binding to one exposed antigenic determinant on antigens. Clone Expand Expand MORE MORE Clonal Expansion (Memory Cells)

  33. X EXTERNAL EXTERNAL ANTIGENIC DETERMINANTS bind to Specific B Lymphocyte Clones

  34. All cells in this “clone” of B lymphocytes (BL) produce antibodies on their surface that interact with only one type ofAntigenic Determinant. Antigen B lymphocytes interact with an exposed antigenic determinant via antibody-receptors on their surface.

  35. Antibody On the B cell surface Antigenic Determinant The Antigen

  36. One antigenic molecule may have several different Exposed ANTIGENIC DETERMINANTS Example of Three (exposed) Antigenic Determinants on this foreign protein.

  37. B cell Clone # 1 B cell Clone # 2 B cell Clone # 3 A Separate Antibody Response results (at the same time) to each of these exposed antigenic determinants on this one antigenic molecule

  38. We term these B Cell Host Responses and the resulting production of Specific Antibody Responses as Humoral (Fluid) Immunity

  39. Humoral Immunity Exposed Antigenic Determinant + BL Specific Clonal Response

  40. B lymphocytes interact with exposed antigenic determinants via the antibody receptors they produce on their surface. So how large must an antigenic determinant be to be “seen” by a B Lymphocyte?

  41. Exposed Antigenic Determinants are Comprised of at least Five to Six amino acids

  42. - + + - Antibody On the B cell surface For B cell antibody, Each Antigenic Site (Determinant) is a function of 1) Non-Identity with any Host Substance 2) Outside Molecular Exposure outside charges and its conformation (must fit into the specific binding site of Antibody) Antigenic Determinant Rest of the Antigen Now the --B Cell may become activated

  43. One clone of B lymphocytes is activated by One Antigenic Determinant Clone 1 Clone 2 Clone 3

  44. 2,000 Antibodies per second per plasma cell Live only two or three days

  45. The clones of B Lymphocytes that bind with the highest affinity to the antigenic determinant are stimulated the most

  46. Now we will discuss T lymphocytes

  47. TLymphocyte Clonal Diversification is in the Thymus & And occurs in the Absence of foreign antigens

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