医学免疫学课件：补体系统与自身免疫病

1、The role of complement system in autoimmune diseaseThe role of complement system in autoimmune diseaseIntroductionThe role of complement system in some diseasessystemic lupus erythematosus (SLE)Glomerular Diseases Dependent on Complement Activation Atypical hemolytic uremic syndrome (aHUS) MPGNAutoi

2、mmune hemolytic anemia (AIHA) W-AIHA CAD PCHThe therapy targeting complement system Eculizumab TNT003 Cp40IntroductionThe activation pathways and regulation of complement systemIntroductionThe functions of complement systemOpsonizationClearance of IcsConnection of innate immunity and adaptive immuni

3、tyTake part in the activation and proliferation of adaptive immunitySystemic lupus erythematosus (SLE)Manifestations skin rashes, chronic fatigue , arthritis ,severe glomerulonephritis, serositisEpidemiology approximately 70 per 100 000 but varies between countries, populations ,610 times increased

4、frequency in women.Characteristics Autoantibodies directed against DNA,histones ,certain cytoplasmic componentsComplement system deficiency in SLE pathogenesisComplement Deficiencies in Systemic Lupus Erythematosus.Angela R. Bryan & Eveline Y. Wu Springer Science+Business Media New York 10 May 2014C

5、1q deficiency in SLE pathogenesisClinical presentation of human C1q deficiency: How much of a lupus? Mihaela Stegert a, Merete Bock a, Marten Trendelenburg Molecular Immunology 67 (2015) 311The role of complement system in the formation of autoantibody The clearance hypothesisA protective role for i

6、nnate immunity in systemic lupus erythematosusMichael C. CarrollThe role of complement system in the formation of autoantibody The concerns in clearance hypothesisdeficiency in C3 is only a minor susceptibility factor for SLE compared with deficiency in C1q or C4.it implies that selfreactive mature

7、lymphocytes are present in the circulation and respond when exposed to SLE self-antigens.innate immunity seem not to be enough in concealing or sequestering all of the apoptotic debris that is released from dying cells.Complement enhances the adaptive immune response to non-self antigenA protective

8、role for innate immunity in systemic lupus erythematosusMichael C. CarrollThe role of complement system in the formation of autoantibody The tolerance hypothesisA protective role for innate immunity in systemic lupus erythematosusMichael C. CarrollThe role of complement system in the formation of au

9、toantibody A Critical Role for Complement in Maintenance of Self-ToleranceA Critical Role for Complement in Maintenance of Self-Tolerance. Andrey P. Prodeus, Siegfried Goerg,Li-Ming Shen etal. Immunity, Vol. 9, 721731, November 1998.Model describing the association of SLE and complement deficiencyAu

10、toantibody and complement system mediated pathogenesis of SLEA protective role for innate immunity in systemic lupus erythematosusMichael C. CarrollHemolytic uremic syndrome (HUS)Histologic features in aHUSGenetic abnormalities associated with aHUSGlomerular Diseases Dependent on Complement Activati

11、on, Including Atypical Hemolytic Uremic Syndrome,Membranoproliferative Glomerulonephritis, and C3 Glomerulopathy. Marina Noris, PhD,1 and Giuseppe Remuzzi, MD, FRCP AJKD 2015Combined complement abnormalities in aHUSCombined Complement Gene Mutations in Atypical Hemolytic Uremic Syndrome InfluenceCli

12、nical Phenotype. Elena Bresin,Erica Rurali, Jessica Caprioli. J Am Soc Nephrol 24: 475486, 2013.Impaired regulation of the alternative pathway result in aHUSAutoimmune hemolytic anemia (AIHA)Mechanisms of erythrocyte destruction in CADRed Blood Cell Destruction in Autoimmune Hemolytic Anemia: Role o

13、f Complement and Potential New Targets for Therapy. Sigbjorn Berentsen and Tatjana Sundic . BioMed Research International 2015Therapy targeting the complementEculizumab in atypical hemolyticuremic syndrome therapyTerminal Complement Inhibitor Eculizumab in Atypical HemolyticUremic Syndrome. C.M. Leg

14、endre, C. Licht, P. Muus, L.A. Greenbaum etal. Massachusetts Medical Society 2013.Therapy targeting the complementTNT003 in CAD therapyTNT003, an inhibitor of the serine protease C1s, prevents complementactivation induced by cold agglutinins. Ju Shi, Eileen L. Rose, Andrew Singh, Sami Hussain, Nancy

15、 E. The American Society of Hematology. December 5, 2015 hypocomplementemic for upstream CP components CAD patient plasmaTNT003, an inhibitor of the serine protease C1s, prevents complement activation induced by cold agglutinins. Ju Shi, Eileen L. Rose, Andrew Singh, Sami Hussain, Nancy E. The American Society of Hematology. December 5, 2015Therapy targeting the complementcompstatin Cp40 in PNH ther