1 / 97

Sri Ram .P Date: 11/25/03 Course: Scientific Discovery Instructor: Dr. A. Vankley

Sri Ram .P Date: 11/25/03 Course: Scientific Discovery Instructor: Dr. A. Vankley. Cell Mediated Immunity. “Discoveries concerning the specificities of Cell Mediated Immune defenses and their implications ”. Immunity?. Foreign Invaders. Self Markers. Markers of Non-Self.

joy
Download Presentation

Sri Ram .P Date: 11/25/03 Course: Scientific Discovery Instructor: Dr. A. Vankley

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Sri Ram .PDate: 11/25/03Course: Scientific Discovery Instructor: Dr. A. Vankley

  2. Cell Mediated Immunity “Discoveries concerning the specificities of Cell Mediated Immune defenses and their implications ”

  3. Immunity?

  4. Foreign Invaders

  5. Self Markers

  6. Markers of Non-Self

  7. Organs and tissues of the immune system

  8. Lymphatic vessels form a circulatory system that operates in close partnership with blood circulation.

  9. Lymph Node

  10. Cells of the Immune System

  11. B cells become plasma cells, which produce antibodies when a foreign antigen triggers the immune response.

  12. Antibody

  13. Antibodies produced by cells of the immune system recognize foreign antigens and mark them for destruction.

  14. Activation of B cells to make antibody

  15. T lymphocytes become CD4+ or helper T cells, or they can become CD8+ cells, which in turn can become killer T cells, also called cytotoxic T cells.

  16. Activation of helper T cells

  17. Activation of cytotoxic T cells

  18. Cytokines Complement

  19. Natural Killer cells , Phagocytes and Granulocytes asa

  20. Immunity and Cancer

  21. Human Tissue Typing for Organ Transplants

  22. Rolf M. Zinkernagel

  23. Rolf M. Zinkernagel • Born: January 6, 1944, Basel, Switzerland • Primary and Secondary Education in and around Basel. • 1962-68:University of Basel, Faculty of Medicine • 1969- Began his life as Surgeon in Basel but soon realized this was not his field. • 1969-70:Postdoctoral Fellow, Laboratory for Electron Microscopy, Institute of Anatomy, University of Basel

  24. Rolf M. Zinkernagel • 1971-1973 Postdoctoral Fellow, Institute of Biochemistry, University of Lausanne, Switzerland • He learnt his immunology here. • He also familiarized himself with the 51-Cr. Release assay to study the immune mechanism destruction of host cells. • His work with infectious agents and immunity studies motivated him for further study .

  25. Rolf M. Zinkernagel • 1973-75:Visiting Fellow, Department of Microbiology, The John Curtin School of Medical Research, Australian National University, Canberra, Australia • 1976-79:Associate (Assistant Professor), Department of Immunopathology, Research Institute of Scripps Clinic, La Jolla, California

  26. Rolf M. Zinkernagel • 1979-88:Associate Professor, Department of Pathology, University of Zurich, University Hospital, Zurich • 1988-92-Full professor in same place • 1992-Head, Institute of Experimental Immunology, Zurich

  27. Peter C. Doherty

  28. Peter C. Doherty • Born: October 15, 1940, Australia • 1962:BVSc University of Queensland, Australia • 1966:MVSc University of Queensland, Australia • 1967-71:Scientific Officer, Senior Scientific Officer, Department of Experimental Pathology,Moredun Research Institute, Edinburgh, Scotland

  29. Peter C. Doherty • 1972-75:Research Fellow, Department of Microbiology, The John Curtin Schoolof Medical Research, Australian National University, Canberra, Australia • 1975-82: Associate Professor/Professor, The Wistar Institute, Philadelphia, PA • 1982-88:Professor and Head, Department of Experimental Pathology, The John CurtinSchool of Medical Research, Australian National University, Canberra

  30. Peter C. Doherty • 1988:Chairman, Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN • 1992:Adjunct Professor, Departments of Pathology and Pediatrics, University of Tennessee, College of Medicine, Memphis, TN  

  31. Paired Up • Peter Doherty first studied the pathogenesis of Semliki Forest virus infection in the mouse, then switched to the lymphocytic choriomeningitis virus (LCMV) model which was a much more powerful tool for immunological analysis.

  32. Paired Up • Zinkernagel wanted to work with R. Blanden on cell-mediated immunity against Salmonella and Listeria to learn more about the role of cell-mediated versus antibody-dependent immune effector mechanisms in these infectious disease models . But lack of space in the lab paired both of them.

  33. Background In 1960-70s immunology was attempted to be understood in terms of infectious diseases. It was then Largely pre-occupied with antibody and T-cell responses against foreign protein antigens or chemically defined small molecules called haptens.

  34. Background • Mechanism of foreign-organ graft rejection was intensively studied, although the biological function of MHC was largely unclear. • Only few people studied immunity against infectious agents.

  35. Background • Antibacterial and antiviral T-cell mediated immunity and the capacity of immunized cytotoxic CD8+ T cells to destroy either virus infected or allogeneic target cells in vitro- was the work in progress at JCSMR.

  36. Techniques and Study • Doherty and Zinkernagel jointly begin work on CMI in LCMV (Lymphocytic choriomeningitis virus). • 51 cr. Release assays as cytotoxicity assay was used by Zinkernagel. • Doherty was efficient in cannulation and could draw few ml of CSF from cisterna magna of the mice.

  37. Techniques and Study • Whether inflammatory cells in the CSF of mice infected intra cerebrally with LCMV were cytolytic in vitro and whether there was any correlation between cytotoxic T- cell activity and severity of choriomeningitis .

  38. Observations • Cytotoxic T cells specifically destroying LCMV infected target cells could be found in CSF of normal mice but not in nude mice lacking thymus and T-cells. • T-cells probably also destroyed infected meningeal and ependymal cells in vivo and this was the pathogenic mechanism causing choriomeningitis.

  39. Observations • The findings were published in the Journal of Experimental Medicine in March 1973. • Same journal had a paper showing mice with different major histocompatibility gene complexes differed in susceptibility to LCMV after cerebral infection. • This prompted to experiment further on this.

  40. Experiment • 6-8 mice of inbred and cross-bred strains were infected intra cerebrally with LCMV. • 2 of each were sacrificed on day 7 after infection when first mouse became sick. –to test antiviral cytotoxic T –cell activities in spleens. • Remaining mice were monitored for lethal disease during next 10days .

  41. Experiment • All mice died in course of time. • But only some generated virus-specific cytotoxic activity that was measurable in vitro. • Result- Either cytotoxic T-cells have nothing to do with choriomeningitis or the test was inadequate.

  42. Reassessment • Mouse L-929 cells (fibroblast cell lines) were used as target cells to assess cytotoxic T-cell activity. • Fortunately the mouse CBA strain and the L-cells derived from mouse strain C3H were closely related. • Both possessed the same MHC-molecules (H-2k).

  43. Reassessment • Studying further, LCMV -immune spleen cells from all mice that possessed H-2k haplotype (as do CBA mice) including the cross breeds with H-2k lysed L-929 cells infected with virus. • But did not lyse uninfected targets or those infected with third-party virus. • All spleen cells derived from immunized mice that were not of H-2k type failed to do so.

  44. Further Studies • Two additional experiments showed that LCMV immune lymphocytes from non-H2k strains of mice were able to lyse LCMV infected target cells of same MHC –type. • LCMV did not infect these cell lines. • Used macrophages from the peritoneum of the mice as target cells. Adhered to plastic, readily infectable and labeled with Cr 51.

  45. Further Studies • Criss-cross experiments showed that LCMV immune T-cells from H-2b mice lyse LCMV-infected macrophages of H-2b origin but not those of other H-2 types and vice versa. • These findings were reported in December to Nature and were published in April,1974

  46. Similar Finding • TNP-specific cytotoxic T cells lysed syngeneic TNP-lated targets more efficiently than allogeneic TNP-lated targets. • European journal of immunology –same time . But independent.

More Related