Presentation on theme: "History of Immunology Core Module Immunology"— Presentation transcript:
1 History of Immunology Core Module Immunology Doctoral Training Group GK1660Erlangen 2011History of ImmunologyComments – Mitchell & Miller, JEM II. 1968i(Receptor Editing)Hans-Martin JäckDivision of Molecular ImmunologyDept. Of Internal Medicine IIINikolaus-Fiebiger-CenterUniversity of Erlangen-Nürnberg
2 The Journal of Experimental Medicine 128: 821-37 (1968) Jaques MillerBorn 1931 NiceAustralia
3 What was know about the involvement of cells in tiggering antbody responses Pre 1968
12 Claman (1966)Bone marrow and thymus cells are required for formation of antibody-secreting cells
13 Do antibody-secreting cells come from the thymus or the bone marrow? 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 MillerBorn 1931 NiceAustralia
15 Experimental Set-UpRestored of hematopetic system by transplanting bone marrow cells into lethally irradiated miceATxBM mice (for Adult Thymectomized, Bone-Marrow estored).Bone marrow can have different marker than thymus cellsImmunological equivalent to neonatally tymectomized miceUsed anti-H2 antibodies to distinguish between thymus- and bone marrow- derived cellsTranser 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 mentionningof the the termsB lymphocytesand T lymphocytes????
17 TDLs complete function of thymus TDLs restore efficiently formation ofantibody-secreting cells
18 Bone marrow cells develop into ASC Hypothesis. ASC originate form bone marrow cellsStrain H2ATxBM Host CBA H-2dBM CBA H-2dTDL (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 intoantibody-forming cells, while the T-cells perform a "helper" function”
21 How do T cells help B cells to develop into antibody-secreting cells?? What next?How do T cells help B cells to develop intoantibody-secreting cells??
23 Peptid in Bindungsspalte MHC MoleculesMHC IMHC IIPeptidbindungsspaltePeptid in BindungsspalteJaneway
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-GensMaus:H-2Kb, b-Allel des Klasse I K-GensI-Ak, k-Allel des Klasse II A-GensKoordinierte Expression(alle Gene werden exprimiert)Ko-dominante Expression(beide Allele werden exprimiert)
28 Ig Loci in mice H locus k locus l locus ca. 2.5 Mb (mouse) stem cell V segmentsD segmentsJ segmentsCstem cellk locusV segmentsJ segmentsCkKappa deleting elementsl locusGerdes 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
30 Does BCR has to reach the surface torecognize self-antigen Problems:Gene was deleted in ALL cells (genomic KO). Effect on e.g. Ab production could come from B cells or other cellsDoes BCR has to reach the surface torecognize self-antigenBone marrowFetal liverRecipentDonorRecipients 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.