自身免疫性疾病英五班

1、autoimmunity and autoimmune diseasesguangjie chen dept. of immunology and microbiology2015autoimmunity is defined as an acquired immune reactivity against self antigensthe normal physiological activityessence-autoimmune responselow affinity igm-cd5+b1- “natural” ab spectrumautoimmune diseases occur

2、when autoimmune responses lead to tissue damage the pathological activityessence-autoimmune responseimmunological tolerance fails to eliminate or control pathogenic self-reactive lymphocytes breaking of self-tolerancei. the features and classification of aid1. features 2. classification organ specif

3、ic nonorgan specificii. the pathological mechanism of aid1. autoantibody binding to cell membrane 2. autoantibody binding to membrane receptor3. autoantibody binding to extracellular components4. the effect of immune complex deposition5. the effect of autoreactive t celltype ii hypersensitivity（auto

4、antibody)1. the effect of autoantibody binding to cell membrane （igm、igg） autoimmune hemolytic anemia thrombocytopenic purpura hemolytic disease of the newborn induced by rhesus incompatibility2. the effect of autoantibody to membrane receptor myasthenia gravis graves diseasethyroid epithelial cellt

5、sh-rtsht3、t4anti-tsh-r abfigure 13-29 part 1 of 23. the effect of autoantibody to extracellular components goodpastures syndrome * anti basement membrane（kidney, lung）type iv collagen ab4. the effect of immune complex deposition * type iii hypersensitivity(1) sle（2）ra(2) ra5. the effect of autoreact

6、ive t cell * type iv hypersensitivitymultiple sclerosis(ms）th1、tc、mbptype i diabetes mellitus tc cellautoimmunemechanismsin msiii. pathogenic factors related to aid1. antigen-related factors releasing of sequestered antigen alteration of self antigen properties molecular mimicrycommon antigencross r

7、eactionstreptococcuskidney, heart epitope spreading2. abnormalities of immune regulation failure of self-toleranceabul k. abbas et al. cellular and molecular immunology, 7th edition, elsevier saunders broken central and peripheral toleranceabul k. abbas et al. cellular and molecular immunology, 7th

8、edition, elsevier saundersautoantigensautoantigen induced t cell expansionautoimmune lymphoproliferative syndrome , alps abnormal expression of fas/fasl polyclonal activation of t and b cellsabul k. abbas et al. cellular and molecular immunology, 7th edition, elsevier saunders dysfunction of treg ab

9、normal expression of mhc-ii3. genetic factors association of hla with autoimmune other genes c1q, c4 gene deficiency：sle dnase deficiency ：sle mutant ctla-4：diabetes4. other factors gender age environment factoriv. immunological control strategies deletion factors which induce abnormal self-toleranc

10、e inhibition of immune response to autoag rebuilding self-tolerance1. control of infection2. administration of immunosuppressive drug3. antibodies4. autoagautoreactivet cellsynovial fibroblastmifn-, il-17il-1, il-15il-1, tnf-chondrocyteosteoclastmmps, il-6, il-8, gm-csfcartilage and bone destruction

11、tnf inhibitorsil-1 inhibitoril-6 inhibitororal tolerancet cell vaccinemmpst cell costimulatory blockers archivum immunologiae et therapiae experimentalis (aite), 2010, 58：27-36targetname of therapeuticproduct of descriptionstage of developmentcurrenttnf-etanerceptsoluble p75 tnfrhuman igg1fc fusion

12、proteinlisencedinfliximabchimeric mab specific for tnf-lisencedadalimumabhumanized mab specific for tnf-lisencedil-1anakinrail-1ralisencedil-6tocilizumabhumanized mab specific for il-6rphase iii clinical trialsin perspectiveil-1amg 108humanized mab specific for il-1phase ii clinical trialsil-15humaxil-15 (amg 714)humax il-15 (amg 714)phase ii clinical trialsil-17lubberts e (2008)il-21andersson ak et al (2008)ar