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Hans-Martin Jäck Division of Molecular Immunology Dept. Of Internal Medicine III

Core Module Immunology Doctoral Training Group GK1660 Erlangen  2011. History of Immunology Comments – Mitchell & Miller, JEM II. 1968i (Receptor Editing). Hans-Martin Jäck Division of Molecular Immunology Dept. Of Internal Medicine III Nikolaus-Fiebiger-Center

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Hans-Martin Jäck Division of Molecular Immunology Dept. Of Internal Medicine III

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  1. Core Module Immunology Doctoral Training Group GK1660 Erlangen  2011 History of Immunology Comments – Mitchell & Miller, JEM II. 1968i (Receptor Editing) Hans-Martin Jäck Division of Molecular Immunology Dept. Of Internal Medicine III Nikolaus-Fiebiger-Center University of Erlangen-Nürnberg

  2. The Journal of Experimental Medicine 128: 821-37 (1968) Jaques Miller Born 1931 Nice Australia

  3. What was know about the involvement of cells in tiggering antbody responses Pre 1968

  4. Mice

  5. Miller 1961 Thymus is required for transplant rejection

  6. Jerne Plaque Assay 1963 Science (1963), p. 405 Antibody-secreting cells can easily be visualized by plaques

  7. Miller 1965: Thmyus and antibodies Thymus cells are required for producing antibody secreting cells

  8. Chicken

  9. Click 1955: Bursa and antibodies J. Poultry Sci. Bursa cells are required for producing antibody secreting cells

  10. Cooper & Good (1965) chicken Bursa are required and thymus are important for effciceint antibody production

  11. Mice

  12. Claman (1966) Bone marrow and thymus cells are required for formation of antibody-secreting cells

  13. The big question: Do antibody-secreting cells come from the thymus or the bone marrow?

  14. The Journal of Experimental Medicine 128: 821-37 (1968) Jaques Miller Born 1931 Nice Australia

  15. Experimental Set-Up • Restored of hematopetic system by transplanting bone marrow cells into lethally irradiated mice • ATxBM mice (for Adult Thymectomized, Bone-Marrow estored). • Bone marrow can have different marker than thymus cells • Immunological equivalent to neonatally tymectomized mice • Used anti-H2 antibodies to distinguish between thymus- and bone marrow-derived cells • Transer pf thymus and TDL (thoracic duct lymphocytes) • TDL are lymphocyte precursors of immune effector cells (Gowan1958) • TDL more potent in restoring IR than thymus cells

  16. B- and T Lymphocytes (Roitt 1969) The first mentionning of the the terms B lymphocytes and T lymphocytes ????

  17. TDLs complete function of thymus TDLs restore efficiently formation of antibody-secreting cells

  18. Bone marrow cells develop into ASC Hypothesis. ASC originate form bone marrow cells Strain H2 ATxBM Host CBA H-2d BM CBA H-2d TDL (F1) Bl6 x CBA H-2b/d

  19. Bone marrow cells develop into ASC Hypothesis. ASC originate form bone marrow cells

  20. Conclusion - Miller 1968 “While both bone-marrow thymus-derived) Cells are required to generate a humoral response to SRBC, only the bone marrow-derived cells develop into antibody-forming cells, while the T-cells perform a "helper" function”

  21. What next? How do T cells help B cells to develop into antibody-secreting cells??

  22. Brief Sidevisit - MHC Haplotype -

  23. Peptid in Bindungsspalte MHC Molecules MHC I MHC II Peptidbindungs spalte Janeway

  24. MHC Locus - Mouse • Polygenmehrere Gene für eine MHC-Kette • Polymorphmehrere Formen eines Gens (Allels) • Beispiele für Nomenklatur: • Mensch: • HLA-B15, Allel 15 des Klasse I B-Gens • Maus: • H-2Kb, b-Allel des Klasse I K-Gens • I-Ak, k-Allel des Klasse II A-Gens • Koordinierte Expression • (alle Gene werden exprimiert) • Ko-dominante Expression • (beide Allele werden exprimiert)

  25. MHC Locus - Mouse

  26. MHC Haplotypes (Set of alleles) Part 1

  27. MHC Haplotypes (Set of alleles) Part 2

  28. Ig Loci in mice H locus ca. 2.5 Mb (mouse) D segments J segments C V segments stem cell k locus J segments V segments Ck Kappa deleting elements l locus Gerdes and Wabl, 2002

  29. Radiation Chimeras • “an experimentally produced animal containing hemopoeitic cells of a genotype different from that of the rest of the organism” • → has the immunologic characteristics of both host and donor http://www.jrank.org/health/pages/19539/radiation-chimera.html

  30. Problems: • Gene was deleted in ALL cells (genomic KO). Effect on e.g. Ab production could come from B cells or other cells • Does BCR has to reach the surface torecognize self-antigen Bone marrow Fetal liver Recipent Donor • Recipients receives a single dose of radiation that kills the stem cells of the bone marrow and much of the differentiated hemopoeitic tissue. • Recipient receives bone marrow or fetal liver cells from nonirradiated donors. • The injected stem cells home to the recipient's bone marrow sites and begin repopulating them, and ultimately they replace the recipient's hemopoeitic tissues. http://www.jrank.org/health/pages/19539/radiation-chimera.html#ixzz1PVRIg46K

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