自身免疫性疾病2015英五班

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 pathogenic self-reactive lymphocytes,Breaking of self-tolerance,Ehrlichs “Horror autotoxicus”,I. The features and classification of AID,1. Features,2. Classification Organ specific Nonorgan specific,II. The pathological mechanism of AID,1. autoantibody binding to cell membrane 2. autoantibody binding to membrane receptor 3. autoantibody binding to extracellular components 4. The effect of immune complex deposition 5. The effect of autoreactive T cell,Type II hypersensitivity（autoantibody) The effect of autoantibody binding to cell membrane （IgM、IgG） Autoimmune hemolytic anemia thrombocytopenic purpura Hemolytic disease of the newborn induced by Rhesus incompatibility,The effect of autoantibody to membrane receptor Myasthenia gravis Graves disease,Figure 13-29 part 1 of 2,3. The effect of autoantibody to extracellular components Goodpastures syndrome,* anti basement membrane（kidney, lung）type IV collagen Ab,4. The effect of immune complex deposition * Type III hypersensitivity,(1) SLE,（2）RA,(2) RA,5. The effect of autoreactive T cell * Type IV hypersensitivity,Multiple sclerosis(MS） Th1、Tc、MBP Type I diabetes mellitus Tc cell,III. Pathogenic factors related to AID,Antigen-related factors Releasing of sequestered antigen,Alteration of self antigen properties Molecular mimicry common antigencross reaction streptococcuskidney, heart Epitope spreading,2. Abnormalities of immune regulation Failure of self-tolerance,Abul K. abbas et al. Cellular and Molecular Immunology, 7th edition, Elsevier Saunders,Broken central and peripheral tolerance,Abul K. abbas et al. Cellular and Molecular Immunology, 7th edition, Elsevier Saunders,Abnormal expression of Fas/FasL,Polyclonal activation of T and B cells,Abul K. abbas et al. Cellular and Molecular Immunology, 7th edition, Elsevier Saunders,Dysfunction of Treg,Abnormal expression of MHC-II,3. Genetic factors Association of HLA with autoimmune disease,,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 ,Archivum Immunologiae et Therapiae Experimentalis (AITE), 2010, 58：27-36,Archivum Immunologiae et Therapiae Experiment