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Autoimmune inflammation and the Autoimmune inflammation and the human microbiome human microbiome Trevor G. Marshall, Trevor G. Marshall, Trevor G. Marshall, Trevor G. Marshall, Computational microscope Computational microscope


  1. Autoimmune inflammation and the Autoimmune inflammation and the human microbiome human microbiome Trevor G. Marshall, Trevor G. Marshall, Trevor G. Marshall, Trevor G. Marshall,

  2. Computational microscope Computational microscope Computational microscope Computational microscope Computational microscope Computational microscope Computational microscope Computational microscope Computational microscope Computational microscope Computational microscope Computational microscope Computational microscope Computational microscope Computational microscope Computational microscope

  3. Autoantibody was FAB regions of IgG isolated from patient with Graves disease. Extracellular region of Autodock Tools Autodock Tools TSH Receptor Molecular Graphics Lab

  4. FAB regions of IgG Extracellular region of TSH Receptor TSH Receptor

  5. EXAMPLE - EBV EXAMPLE – Tetanus Toxoid “We immortalized human B cell lines “We immortalized human B cell lines "Human-human hybridomas produced "Human-human hybridomas produced from normal individuals and from from lymphocytes of normal patients with malignant or benign individuals yielded seven clones dysglobulinemia with Epstein-Barr virus Barr virus producing monoclonal antibody and examined, after cloning, the reacting with tetanus toxoid. autoantibody reactivities of the of these antibodies cross of these antibodies cross of these antibodies cross of these antibodies cross immunoglobulins secreted by these with diphtheria toxoid. with diphtheria toxoid. with diphtheria toxoid. with diphtheria toxoid. two supernatants were two supernatants were and two others also reacted with and two others also reacted with and two others also reacted with and two others also reacted with and two others also reacted with and two others also reacted with and two others also reacted with and two others also reacted with analyzed by enzyme-immunoassay on a cardiolipin and two with other cardiolipin and two with other cardiolipin and two with other cardiolipin and two with other panel of 13 self and non-self antigens: phospholipids phospholipids phospholipids phospholipids" " " " trinitrobenzenesulfonic acid (TNP), glutamine, L-alanine, L- (M Sutjita, A Hohmann, R tyrosine (GAT), actin, myosin, tubulin, Bradley: Polyspecific albumin, renin, spectrin, transferrin, antibodies to diphtheria and thyroglobulin, myoglobin, peroxidase .. thyroglobulin, myoglobin, peroxidase .. .. .. .. .. .. .. phospholipids. Clin Exp Imm phospholipids. Clin Exp Imm The vast majority of these clones The vast majority of these clones The vast majority of these clones The vast majority of these clones

  6. antibodies recognizing EBNA1 400–413 413 and MAP 121–132 cross- , possibly through a molecular mimicry mechanism. Indeed, the fact that , possibly through a molecular mimicry mechanism. Indeed, the fact that peptides from different pathogens can be cross peptides from different pathogens can be cross-recognized by antibodies targeting epitopes supports the hypothesis that EBV and MAP might trigger epitopes supports the hypothesis that EBV and MAP might trigger autoimmunity through a common target” autoimmunity through a common target” (Mameli G, et al: Epstein-Barr virus and Mycobacterium avium subsp. paratuberculosis peptides are cross Barr virus and Mycobacterium avium subsp. paratuberculosis peptides are cross recognized by anti-myelin basic protein antibodies in multiple sclerosis patients. J Neuroimmunol. myelin basic protein antibodies in multiple sclerosis patients. J Neuroimmunol. Mar Mar 6)

  7. About 110- (not all are functional)

  8. **Gazillion** In Mouse, 17,431 unique 17,431 unique antibodies to date

  9. began development of a mass screening assay began development of a mass screening assay began development of a mass screening assay began development of a mass screening assay to try and determine which of the victims to try and determine which of the victims were most likely to develop disease from that were most likely to develop disease from that exposure. He has developed the ‘ELI exposure. He has developed the ‘ELI Viscero’ tests for Natural Autoantibodies Natural Autoantibodies

  10. Marker of Vasculitis Profiles of serum Natural auto-Abs

  11. CD19+

  12. Antibodies are far more complex and numerous than we ever Antibodies are far more complex and numerous than we ever dreamed was possible dreamed was possible dreamed was possible dreamed was possible Human antibodies are mostly polyspecific, ‘autoantibodies’ is Human antibodies are mostly polyspecific, ‘autoantibodies’ is a misnomer indicating their potential for ‘collateral damage’ a misnomer indicating their potential for ‘collateral damage’ The most likely trigger for persistent antibody production in The most likely trigger for persistent antibody production in The most likely trigger for persistent antibody production in The most likely trigger for persistent antibody production in humans are the microbes comprising the Human Microbiome humans are the microbes comprising the Human Microbiome The failure of innate immunity will lead to energetic The failure of innate immunity will lead to energetic stimulation of antibody, and hence autoantibody, production stimulation of antibody, and hence autoantibody, production Stimulation of the innate innate immune system against the immune system against the

  13. Question Time Question Time Question Time Question Time Question Time Question Time Question Time Question Time

  14. Luc Montagnier, Nobel Prize in Physiology or Medicine in 2008 Luc Montagnier, Nobel Prize in Physiology or Medicine in 2008 “Digital transmission of bacterial DNA in living cells” “Digital transmission of bacterial DNA in living cells” Giuseppe Vitiello, Professor of Theoretical Physics, University of Giuseppe Vitiello, Professor of Theoretical Physics, University of Salerno Salerno “A quantum field approach to living matter: why fields? why quantum?” “A quantum field approach to living matter: why fields? why quantum?” “A quantum field approach to living matter: why fields? why quantum?” “A quantum field approach to living matter: why fields? why quantum?”

  15. The YouTube videos I took can be viewed at these addresses: The YouTube videos I took can be viewed at these addresses: Luc Montagnier: https://www.youtube.com/watch?v=mYcNXjdPXGU Luc Montagnier: https://www.youtube.com/watch?v=mYcNXjdPXGU Luc Montagnier: https://www.youtube.com/watch?v=mYcNXjdPXGU Luc Montagnier: https://www.youtube.com/watch?v=mYcNXjdPXGU Prof Marc Henry: https://www.youtube.com/watch?v=V0Qrn Prof Marc Henry: https://www.youtube.com/watch?v=V0Qrn Prof Carlo Ventura: https://www.youtube.com/watch?v=O3lvFJgXScM Prof Carlo Ventura: https://www.youtube.com/watch?v=O3lvFJgXScM Prof Guiseppe Vitiello: https://www.youtube.com/watch?v=s4s Prof Guiseppe Vitiello: https://www.youtube.com/watch?v=s4s fEYmZFo fEYmZFo

  16. Known to be attacked by elements of Microbiome (eg. M. leprae

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