autoimmune new uki.ppt
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AUTOIMMUNE DISORDER
Ciri sistem Ciri sistem IMUN: IMUN: Spesifik, Memori, Kenal-diri.Spesifik, Memori, Kenal-diri.
SPESIFIK: seseorang yang dibuat kebal SPESIFIK: seseorang yang dibuat kebal terhadap Virus Hepatitis A, tidak kebal terhadap Virus Hepatitis A, tidak kebal terhadap infeksi Virus Hepatitis Bterhadap infeksi Virus Hepatitis B
MEMORI: seseorang yang kebal terhadap MEMORI: seseorang yang kebal terhadap Virus Hepatitis A akan dengan cepat Virus Hepatitis A akan dengan cepat melawan bila terinfeksi virus tersebut melawan bila terinfeksi virus tersebut
KENAL-DIRI: segala sesuatu yang dikenal KENAL-DIRI: segala sesuatu yang dikenal sejak janin adalah milik sendirisejak janin adalah milik sendiri
Self vs non-self Antigen
Major histocompatibility complex (MHC) genes that code the antigens for tissue and blood
compatibility in mammals Human leucocyte antigens (HLA)
Proteins/antigens expressed on cell surfaces of ‘Self’ in humans
Important role in antigen presentation Class I: A, B, C; Class II: D, DR
Important ConceptsImportant ConceptsImportant ConceptsImportant Concepts
AUTOIMUNITASAUTOIMUNITAS Respon imun terhadap atigen Respon imun terhadap atigen
diri(diri(selfself)) Penyakit autoimun ialah kerusakan Penyakit autoimun ialah kerusakan
jaringan akibatjaringan akibat PROSES IMUNOLOGIK PROSES IMUNOLOGIK Bentuk penyakit: Bentuk penyakit: spesifikspesifik organ, organ,
thyroid; dan thyroid; dan nonnon-spesifik organ, SLE-spesifik organ, SLE Umur 15-65 th, Umur 15-65 th, F:M 8:1 F:M 8:1 pada SLE, pada SLE,
M> ankylosing spondylitisM> ankylosing spondylitis
AUTOIMUNITAS, AUTOIMUNITAS, etiologi . .etiologi . .
AUTOIMUNITAS, AUTOIMUNITAS, etiologi . .etiologi . .
Breakdown of TOLERANCE: thymic, gagal seleksi negatif tdk memproduksi peptida di permukaan sel T; peripheral, self Ag invisible, mimicry
Faktor genetik, terkait dengan MHC Faktor lingkungan, infeksi, obat, UV
Mechanisms of developmentMechanisms of development (1) (1)
11. . Brekdown of self toleranceBrekdown of self tolerance 2. 2. Molecular mimicry and T cell bypassMolecular mimicry and T cell bypass
cross reacting antigen of microbial antigen cross reacting antigen of microbial antigen autoantibody response;autoantibody response;
e.ge.g. heart autoantibody in post group A streptococcal . heart autoantibody in post group A streptococcal
rheumatic fever;rheumatic fever; 33. Defective regulation mediated via helper T cells. Defective regulation mediated via helper T cells
microbial infection microbial infection Th1 (pro inflammatory cytokines) Th1 (pro inflammatory cytokines)
and Th2 (anti inflammatory cytokines and antibody formation), and Th2 (anti inflammatory cytokines and antibody formation),
predominance of Th1 or Th2 due certain situation (e.g. pregnancy)predominance of Th1 or Th2 due certain situation (e.g. pregnancy)
autoimmunity (RA and SLE);autoimmunity (RA and SLE); 4. 4. Polyclonal activation via microbial antigensPolyclonal activation via microbial antigens
some microbes some microbes polyclonal activators e.g. E. coli LPS, EBV; polyclonal activators e.g. E. coli LPS, EBV;
I.M. (infectious mononucleosis) I.M. (infectious mononucleosis) anti DNA antibody; anti DNA antibody;
Mechanisms of development (2)Mechanisms of development (2) 5. Modification of 5. Modification of cell surfaces cell surfaces by microbes and drugsby microbes and drugs viruses or drugs viruses or drugs attached to surface in hapten like attached to surface in hapten like manner manner alter specificity; alter specificity; e.g. thrombocytopenia and anemia in viral infection ore.g. thrombocytopenia and anemia in viral infection or drug induced;drug induced; 6. Availability of normally 6. Availability of normally sequestered sequestered self antigenself antigen anatomically separated (sequestered) antigensanatomically separated (sequestered) antigens (lens, CNS, thyroid, testes) (lens, CNS, thyroid, testes) trauma or infection trauma or infection released or presented released or presented autoimmunity; autoimmunity; 7. Dysregulation of the 7. Dysregulation of the idiotypeidiotype network network immune response to hormone immune response to hormone anti hormone anti hormone antibody antibody anti-idiotype antibody anti-idiotype antibody interact with the receptor interact with the receptor autoimmune disease;autoimmune disease; e.g. Antibodies to insulin and acetylcholine receptore.g. Antibodies to insulin and acetylcholine receptor
(Adapted from Lydyard PM et al Instant Notes in Immunology 2000)
PATHOGENESIS AUTOIMMUNE
Spectrum / Classification of Spectrum / Classification of Autoimmune DIseaseAutoimmune DIsease
1. 1. Organ specificOrgan specific:: = involving certain organ with auto-= involving certain organ with auto- antibody specific to that organ (antibody specific to that organ (organorgan specific autoantibodyspecific autoantibody);); 2. 2. Non-organ specificNon-organ specific:: = involving various organs with auto-= involving various organs with auto- antibodies specific to various organsantibodies specific to various organs ((non-organ specific autoantibodiesnon-organ specific autoantibodies);); 3. 3. Combination / overlap between Combination / overlap between adad 1) and 1) and adad 2): 2): = involving more than one type with both = involving more than one type with both types of autoantibodies types of autoantibodies
(1). Organ specific auto-immune diseases (1). Organ specific auto-immune diseases
DiseaseDisease
Organ specificOrgan specific:: 1. Myasthenia gravis 1. Myasthenia gravis 2. Graves’ disease2. Graves’ disease 3. Hashimoto’s thyroiditis 3. Hashimoto’s thyroiditis 4. Type I diabetes4. Type I diabetes 5. Pernicious anemia5. Pernicious anemia 6. Addison’s disease6. Addison’s disease 7. Pemphigus vulgaris7. Pemphigus vulgaris 8. Bulbous pemphigoid8. Bulbous pemphigoid 9. Vitiligo9. Vitiligo 10. Autoimmune hepatitis10. Autoimmune hepatitis 11. Autoimmune hemolytic anemia 11. Autoimmune hemolytic anemia
Autoantigens targetedAutoantigens targeted
1. Acethylcholine receptor1. Acethylcholine receptor 2. Thyroid stimulating hormone rec.2. Thyroid stimulating hormone rec. 3. Thyroid peroxidase thyroglobulin3. Thyroid peroxidase thyroglobulin 4. Islet cell cytopl. Insulin, GAD4. Islet cell cytopl. Insulin, GAD 5. HK ATPase (GPP), intrinsic factor5. HK ATPase (GPP), intrinsic factor 6. 17 6. 17 hydroxylasehydroxylase 7. 130 kDa cadherin adhesion mol.7. 130 kDa cadherin adhesion mol. 8. 160 kDa & 230 kDa cell adhesion8. 160 kDa & 230 kDa cell adhesion moleculesmolecules 9. Melanocyte cytoplasmic antigen9. Melanocyte cytoplasmic antigen 10. Asialoglycoprotein rec,10. Asialoglycoprotein rec, Cytochrome P450206Cytochrome P450206 11. Red blood cell surface antigen11. Red blood cell surface antigen
(Adapted from Lydyard PM et al. Instant Notes in Immunology 2000)
(Adapted from Lydyard PM et al. Instant Notes in Immunology 2000)
(2). Non-organ specific autoimmune diseases(2). Non-organ specific autoimmune diseases
DiseaseDisease
Non-organ specificNon-organ specific 1. Rheumatoid arthritis1. Rheumatoid arthritis 2. Systemic lupus2. Systemic lupus erythematosuserythematosus
3. Sjogren’s syndrome3. Sjogren’s syndrome 4. Systemic sclerosis4. Systemic sclerosis
5. Mixed connective tissue5. Mixed connective tissue diseasedisease 6. Polymyositis6. Polymyositis
Main autoantigens targetedMain autoantigens targeted
1. IgG1. IgG 2. ds DNA, Sm, SS-A (Ro: a2. ds DNA, Sm, SS-A (Ro: a 60 kDa ribonucleo- 60 kDa ribonucleo- protein), SS-B (La: a 47 kDa protein), SS-B (La: a 47 kDa ribo-nucleoprotein), histonesribo-nucleoprotein), histones 3. SS-A, SS-B3. SS-A, SS-B 4. DNA topoisomerase I,4. DNA topoisomerase I, centromerecentromere 5. 70 kDa small nuclear ribo-5. 70 kDa small nuclear ribo- nucleoproteinnucleoprotein 6. tRNA synthetase6. tRNA synthetase
(3). Overlap between organ- and non-organ (3). Overlap between organ- and non-organ specific autoimmune diseases specific autoimmune diseases
DiseaseDisease Overlap of organ- non-Overlap of organ- non-
organ specificorgan specific 1. Primary biliary cirrhosis1. Primary biliary cirrhosis
2. Systemic lupus 2. Systemic lupus erythematosuserythematosus
Main autoantigens targetedMain autoantigens targeted
1. Mitochondrial pyruvate1. Mitochondrial pyruvate dehydrogenasedehydrogenase 2. Non-collagenous domain2. Non-collagenous domain of type IV collagen in renalof type IV collagen in renal and lung basementand lung basement membranemembrane
(4). Autoimmune diseases might occur in more than one type
e.g. thyroiditis autoimmune disease and gastric autoimmunity
Pathogenesis of autoimmune Pathogenesis of autoimmune diseasesdiseases
1. primarily by antibody (auto-antibody):1. primarily by antibody (auto-antibody): e.g.e.g. hemolytic anemia hemolytic anemia 2. primarily by cellular immunity (auto-2. primarily by cellular immunity (auto- reactive T cell):reactive T cell): e.g.e.g. multiple sclerosis multiple sclerosis 3. combination of antibody and cell mediated3. combination of antibody and cell mediated immunity:immunity: e.g.e.g. rheumatoid arthritis rheumatoid arthritis
SLESLE
AMERICAN COLLEGE OF AMERICAN COLLEGE OF RHEUMATOLOGY CRITERIARHEUMATOLOGY CRITERIAAMERICAN COLLEGE OF AMERICAN COLLEGE OF RHEUMATOLOGY CRITERIARHEUMATOLOGY CRITERIA
“MD SOAP BRAIN”
Lupus band test (direct Lupus band test (direct FAT)FAT)
Lupus band test (direct Lupus band test (direct FAT)FAT)
Nefritis lupusNefritis lupusNefritis lupusNefritis lupus
perempuan dewasa muda rasio perempuan/laki = 5-10:1 50-80% kasus LES 4-8% presentasi awal
Nefritis lupusNefritis lupusNefritis lupusNefritis lupus Manifestasi klinis
o Proteinuria o Hematuria mikroskopik o Sindrom nefritik akuto Sindrom nefrotiko Gagal ginjal
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