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Chapter 18 Autoimmune Diseases 1
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1.Immunological homeostasis: To self Ag, our immune system is in tolerance and immune response won’t take place. Immune tolerance broken up Anti self T cellAnti self B cell Autoimmunity Autoimmune Diseases 2 2.Autoimmune Diseases(AID)
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Overview Autoimmunity: is that immune system plays response to self cells and tissues. This can take place in all the individuals. 3 Autoimmune diseases: Under certain internal and external factors, immune tolerance is broken up and durative autoimmunity produces abnormal immune response to autoantigen that caused self cells and tissue damage or dysfunction. We call this clinical symptoms of autoimmune diseases. Short time autoimmunity response is ubiquitous and can not induce durative damage.
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Section I. Induced factors and mechanism of autoimmune diseases We still don’t know the definite etiological factor. Factors I. Aspect of Ag 1. Ag of immunologically privileged site releasing sympathetic ophthalmia 4
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2. Change of self Ag rheumatoid arthritis abnormal IgG (Ag) anti IgG Ab( IgM, rheumatoid factor) IC IC deposit at synovium of small joints flare, distortion, anchylose, lose motor function. 8
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3. Molecular mimicry: there are some common epitopes between microbes and human cells. When these microbes invade human, immune response can be induced to elimiante them and damange self cells and tissues. post-streptococcal glomerulonephritis 9
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4.Epitope spreading: Dominant epitope and cryptic epitope After immune system play response to a dominant epitope, it may play response to cryptic epitope. This is epitope spreading. 如 SLE- Histon ( H1) - DNA RA , MS 10
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II. Genetic aspect 1.Genotype of HLA is relative with autoimmune disease. ① HLA molecule coded by differential HLA gene can not supply Ag for T cell negative selection. ② HLA molecule coded by differential HLA gene can present pathogen, which is similar with self Ag, preferably. Immune diseases can be induced by molecular mimicry. 12
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Relation between autoimmune diseases with MHC diseases genotype of HLA relative risk ankylosing spondylitis B27 87.4 Acute anterior uveitis B27 10.04 Goodpasture’s syndrome DR2 15.9 MS DR2 4.8 Graves’ disease DR3 3.7 MG DR3 2.5 SLE DR3 5.8 IDDM DR3/DR4 3.2 rheumatoid arthritis DR4 4.2 13
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2.Others gene relative with autoimmune diseases. C1q, C4, DNA enzyme, CTLA-4 et al. III. Other aspects 1.Sex and autoimmune diseases. MS and SLE : female 10-20 fold to male ankylosing spondylitis : male 3 fold to female 2.Age: old age 3. Environmental : cold \moisture\sunshine 14
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Mechanism 1.autoreactive T cell clone delection abnormal 2.Immune ignorance broken up 3.Lympocytes polyclone activation 4.Activated induced cell death (AICD) disorder 5.Regulation T cell abnormal 6.MHC II molecule abnormal expression 15
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Section II. Immunological injury mechanism and typical diseases Etiological factor: anti self Ab and anti self T cell. 16
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Hypersensitivity: as soon as immunity response eliminate Ag, host’s tissue appears physiologic function disorder or even damaged by the response. Autoimmune diseases: hypersensitivity diseases to self Ag. Pathogenesis is same as hypersensitivity. 17 Autoimmune diseases and hypersensitivity
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I. Autoimmune diseases induced by Self Ab 1.Self Ab on cell membrane or adhered on membrane induced autoimmune diseases. Complement activation, Splenic phagocytes phagocytosis, ADCC, Neutrophil activation 18
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2. Autoimmune diseases induced by anti cell surface receptor Ab. ( 1 ) Diseases mediated by stimulating auto-antibodies Graves’ disease Anti- TSHR IgG Effect fetus Plasma exchange transfusion 20
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( 2 ) Diseases mediated by blocking auto-antibodies myasthenia gravis, MG 21
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22 Myasthenia gravis (MG) (anti-AchR, blocking antibodies) In myasthenia gravis the antibodies bind the acetylcholine receptor and blocks the normal binding of acetylcholine, and cause it to be cleared from the surface of the muscle. In addition, the anti-AChR activates complement, which damages the muscle end- plate; the number of acetylcholine receptors declines as the disease progresses.
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3. Diseases mediated by IC Systemic lupus erythematosus, SLE Anti-dsDNA Ab Anti-ssDNA Ab Anti-nucleoprotein Ab Anti-histone Ab Anti-RNA Ab 24
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II. Disease mediated by anti self T cells Insulin-dependent diabetes mellitus, IDDM : CD8 + CTL damage pancreatic islets cells Multiple sclerosis, MS 25
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Section III. Classification and features of Autoimmune disease 26
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Organ specific autoimmune disease Graves disease IDDM Myasthenia Gravis (MG) Systemic autoimmune disease RA SLE 27
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28 Classification of Autoimmune disease
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2.Features of autoimmune disease 29 1. Autoantibody and autoreactive T cell can be detected in patients. 2. Autoantibody and autoreactive T cell playing response to self cells and tissues that induce dysfunction. 3. The recover of patients has relationship with intensity of autoimmune response. 4. The diseases tissues have Ig deposition or lymphocytes infiltration. 5. The diseases can be passive transfered by serum or lymphocytes
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Section IV. Preventive and controlling principle of autoimmune disease 1.Prevent and control microbes infection 2.Immunodepressant utilization Cytokines and CR blocking agent Rheumatoid Arthritis: anti TNF- αmonoclonal Ab (infliximab) 3.Rebulid immunological tolerance to self antigen 30
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Exercise Concept: Autoimmune Autoimmune disease Classification and Features of autoimmune diseases. Preventive and controlling principle of autoimmune disease 31
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