AUTOIMMUNE

DISORDER
 Ciri sistem IMUN:
Spesifik, Memori, Kenal-diri.
SPESIFIK: seseorang yang dibuat kebal
terhadap Virus Hepatitis A, tidak kebal
terhadap infeksi Virus Hepatitis B
MEMORI: seseorang yang kebal terhadap
Virus Hepatitis A akan dengan cepat
melawan bila terinfeksi virus tersebut
KENAL-DIRI: segala sesuatu yang
dikenal sejak janin adalah milik sendiri
 Important Concepts
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
 AUTOIMUNITAS
Respon imun terhadap atigen
diri(self)
Penyakit autoimun ialah kerusakan
jaringan akibat PROSES IMUNOLOGIK
Bentuk penyakit: spesifik organ,
thyroid; dan non-spesifik organ, SLE
Umur 15-65 th, F:M 8:1 pada SLE,
M> ankylosing spondylitis
 AUTOIMUNITAS, 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 development (1)
1. Brekdown of self tolerance
2. Molecular mimicry and T cell bypass
cross reacting antigen of microbial antigen
autoantibody response;
e.g. heart autoantibody in post group A streptococcal
rheumatic fever;
3. Defective regulation mediated via helper T cells
microbial infection Th1 (pro inflammatory cytokines)
and Th2 (anti inflammatory cytokines and antibody formation),
predominance of Th1 or Th2 due certain situation (e.g. pregnancy)
autoimmunity (RA and SLE);
4. Polyclonal activation via microbial antigens
some microbes polyclonal activators e.g. E. coli LPS, EBV;
I.M. (infectious mononucleosis) anti DNA antibody;
 Mechanisms of development (2)
5. Modification of cell surfaces by microbes and drugs
viruses or drugs attached to surface in hapten like
manner alter specificity;
e.g. thrombocytopenia and anemia in viral infection or
drug induced;
6. Availability of normally sequestered self antigen
anatomically separated (sequestered) antigens
(lens, CNS, thyroid, testes) trauma or infection
released or presented autoimmunity;
7. Dysregulation of the idiotype network
immune response to hormone anti hormone
antibody
anti-idiotype antibody interact with the receptor
autoimmune disease;
e.g. Antibodies to insulin and acetylcholine receptor
(Adapted from Lydyard PM et al Instant Notes in Immunology 2000)
PATHOGENESIS
AUTOIMMUNE
 Spectrum / Classification of
Autoimmune DIsease
1. Organ specific:
= involving certain organ with auto-
antibody specific to that organ (organ
specific autoantibody);
2. Non-organ specific:
= involving various organs with auto-
antibodies specific to various organs
(non-organ specific autoantibodies);
3. Combination / overlap between ad 1) and ad 2):
= involving more than one type with both
types of autoantibodies
 (1). Organ specific auto-immune diseases
Disease
Organ specific:
1. Myasthenia gravis
2. Graves disease
3. Hashimotos thyroiditis
4. Type I diabetes
5. Pernicious anemia
6. Addisons disease
7. Pemphigus vulgaris
8. Bulbous pemphigoid
9. Vitiligo
10. Autoimmune hepatitis
11. Autoimmune hemolytic anemia
Autoantigens targeted
1. Acethylcholine receptor
2. Thyroid stimulating hormone rec.
3. Thyroid peroxidase thyroglobulin
4. Islet cell cytopl. Insulin, GAD
5. HK ATPase (GPP), intrinsic factor
6. 17 hydroxylase
7. 130 kDa cadherin adhesion mol.
8. 160 kDa & 230 kDa cell adhesion
molecules
9. Melanocyte cytoplasmic antigen
10. Asialoglycoprotein rec,
Cytochrome P450206
11. 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
Disease
Non-organ specific
1. Rheumatoid arthritis
2. Systemic lupus
erythematosus
3. Sjogrens syndrome
4. Systemic sclerosis
5. Mixed connective tissue
disease
6. Polymyositis
Main autoantigens targeted
1. IgG
2. ds DNA, Sm, SS-A (Ro: a
60 kDa ribonucleo-
protein), SS-B (La: a 47 kDa
ribo-nucleoprotein), histones
3. SS-A, SS-B
4. DNA topoisomerase I,
centromere
5. 70 kDa small nuclear ribo-
nucleoprotein
6. tRNA synthetase
(3). Overlap between organ- and non-organ
specific autoimmune diseases
Disease Main autoantigens targeted
Overlap of organ- non-
organ specific
1. Primary biliary cirrhosis 1. Mitochondrial pyruvate
dehydrogenase
2. Systemic lupus 2. Non-collagenous domain
erythematosus of type IV collagen in renal
and lung basement
membrane
(4). Autoimmune diseases might occur in more than one type
e.g. thyroiditis autoimmune disease and gastric autoimmunity
 Pathogenesis of autoimmune
diseases
1. primarily by antibody (auto-antibody):
e.g. hemolytic anemia
2. primarily by cellular immunity (auto-
reactive T cell):
e.g. multiple sclerosis
3. combination of antibody and cell mediated
immunity:
e.g. rheumatoid arthritis
SLE
 MD SOAP BRAIN
AMERICAN COLLEGE OF RHEUMATOLOGY
CRITERIA
Lupus band test (direct FAT)
 Nefritis lupus

perempuan dewasa muda

rasio perempuan/laki = 5-10:1
50-80% kasus LES
4-8% presentasi awal
 Nefritis lupus
Manifestasi klinis

o Proteinuria
o Hematuria mikroskopik
o Sindrom nefritik akut
o Sindrom nefrotik
o Gagal ginjal
 Type II ADCC/CDC
Antibody-dependent cell-mediated cytotoxicity ADCC

Complement Natural killer cell Macrophage

pathway

Monoclonal
antibody
Fc
receptor
Cell
surface
antigen

Lymphoma cell
Terima
kasih