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Hans-Martin Jäck Division of Molecular Immunology Dept. Of Internal Medicine III Nikolaus-Fiebiger-Center University of Erlangen-Nürnberg History of Immunology.

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Presentation on theme: "Hans-Martin Jäck Division of Molecular Immunology Dept. Of Internal Medicine III Nikolaus-Fiebiger-Center University of Erlangen-Nürnberg History of Immunology."— Presentation transcript:

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

2 The Journal of Experimental Medicine 128: (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 Doctoral Training Group GK University of Erlangen-Nürnberg 5 Miller 1961 Thymus is required for transplant rejection Thymus is required for transplant rejection

6 Doctoral Training Group GK University of Erlangen-Nürnberg 6 Jerne Plaque Assay 1963 Science (1963), p. 405 Antibody-secreting cells can easily be visualized by plaques

7 Doctoral Training Group GK University of Erlangen-Nürnberg 7 Miller 1965: Thmyus and antibodies Thymus cells are required for producing antibody secreting cells

8 Chicken

9 Doctoral Training Group GK University of Erlangen-Nürnberg 9 J. Poultry Sci. Click 1955: Bursa and antibodies Bursa cells are required for producing antibody secreting cells

10 Doctoral Training Group GK University of Erlangen-Nürnberg 10 Cooper & Good (1965) chicken Bursa are required and thymus are important for effciceint antibody production

11 Mice

12 Doctoral Training Group GK University of Erlangen-Nürnberg 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: (1968) Jaques Miller Born 1931 Nice Australia

15 Doctoral Training Group GK University of Erlangen-Nürnberg 15 Experimental Set-Up  Restored of hematopetic system by transplanting bone marrow cells into lethally irradiated mice o ATxBM mice (for Adult Thymectomized, Bone-Marrow estored). o Bone marrow can have different marker than thymus cells o 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) o TDL are lymphocyte precursors of immune effector cells (Gowan1958) o TDL more potent in restoring IR than thymus cells

16 Doctoral Training Group GK University of Erlangen-Nürnberg 16 The first mentionning of the the terms B lymphocytes and T lymphocytes ???? The first mentionning of the the terms B lymphocytes and T lymphocytes ???? B- and T Lymphocytes (Roitt 1969)

17 Doctoral Training Group GK University of Erlangen-Nürnberg 17 TDLs restore efficiently formation of antibody-secreting cells TDLs restore efficiently formation of antibody-secreting cells TDLs complete function of thymus

18 Doctoral Training Group GK University of Erlangen-Nürnberg 18 Strain H2 ATxBM Host CBAH-2d BM CBAH-2d TDL (F1) Bl6 x CBAH-2b/d Bone marrow cells develop into ASC Hypothesis. ASC originate form bone marrow cells

19 Doctoral Training Group GK University of Erlangen-Nürnberg 19 Bone marrow cells develop into ASC Hypothesis. ASC originate form bone marrow cells

20 Doctoral Training Group GK University of Erlangen-Nürnberg 20 “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” “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” Conclusion - Miller 1968

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

22 Brief Sidevisit - MHC Haplotype -

23 Doctoral Training Group GK University of Erlangen-Nürnberg 23 Peptidbindungs spalte MHC I MHC II Janeway Peptid in Bindungsspalte MHC Molecules

24 Doctoral Training Group GK University of Erlangen-Nürnberg 24 MHC Locus - Mouse Polygen mehrere Gene für eine MHC-Kette Polymorph mehrere Formen eines Gens (Allels) Beispiele für Nomenklatur: Mensch: HLA-B15, Allel 15 des Klasse I B-Gens Maus: H-2K b, b-Allel des Klasse I K-Gens I-A k, k-Allel des Klasse II A-Gens Koordinierte Expression (alle Gene werden exprimiert) Ko-dominante Expression (beide Allele werden exprimiert)

25 Doctoral Training Group GK University of Erlangen-Nürnberg 25 MHC Locus - Mouse

26 Doctoral Training Group GK University of Erlangen-Nürnberg 26 MHC Haplotypes (Set of alleles) Part 1

27 Doctoral Training Group GK University of Erlangen-Nürnberg 27 MHC Haplotypes (Set of alleles) Part 2

28 Doctoral Training Group GK University of Erlangen-Nürnberg 28 Ig Loci in mice  locus stem cell J segmentsCC V segments D segments ca. 2.5 Mb (mouse) H locus J segments V segmentsCC  locus Gerdes and Wabl, 2002 Kappa deleting elements

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

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 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. Bone marrow Fetal liver Donor Recipent


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