自身免疫性疾病-2015-英五班.pptVIP

Other genes C1q, C4 gene deficiency：SLE DNase deficiency ：SLE mutant CTLA-4：Diabetes 4. Other factors Gender Age Environment factor IV. Immunological control strategies Deletion factors which induce abnormal self-tolerance Inhibition of immune response to autoAg Rebuilding self-tolerance Control of infection Administration of immunosuppressive drug Antibodies autoAg …… Autoreactive T cell Synovial fibroblast M? IFN-?, IL-17 IL-1, IL-15 IL-1, TNF-? Chondrocyte Osteoclast MMPs, IL-6, IL-8, GM-CSF Cartilage and bone destruction TNF inhibitors IL-1 inhibitor IL-6 inhibitor Oral tolerance T cell vaccine MMPs T cell costimulatory blockers Archivum Immunologiae et Therapiae Experimentalis (AITE), 2010, 58：27-36 Target Name of therapeutic Product of description Stage of development Current TNF-? Etanercept Soluble p75 TNFR–human IgG1Fc fusion protein Lisenced Infliximab Chimeric mAb specific for TNF-? Lisenced Adalimumab Humanized mAb specific for TNF-α Lisenced IL-1 Anakinra IL-1ra Lisenced IL-6 Tocilizumab Humanized mAb specific for IL-6R Phase III clinical trials In perspective IL-1 AMG 108 Humanized mAb specific for IL-1β Phase II clinical trials IL-15 HuMaxIL-15 (AMG 714) HuMax IL-15 (AMG 714) Phase II clinical trials IL-17 Lubberts E (2008) IL-21 Andersson AK et al (2008) Archivum Immunologiae et Therapiae Experimentalis (AITE), 2010, 58：27-36 Key points Definition of autoimmunity and AID Pathogenic factors related to AID Features and pathological mechanism of AID * Autoimmunity and Autoimmune Diseases Guangjie Chen Dept. of Immunology and Microbiology 2015 Autoimmunity is defined as an acquired immune reactivity against self antigens The normal physiological activity essence ----autoimmune response Low affinity IgM----CD5+B1---- “natural” Ab spectrum Autoimmune diseases occur when autoimmune responses lead to tissue damage The pathological activity essence----autoimmune response Immunological tolerance fails to eliminate or control pathoge