AUTOIMMUNE DISEASE

BY
Nova Kurniati.
 Pendahuluan

Autoimunitas : respon imun thd Ag jaringan sendiri

yg disebabkan kegagalan mekanisme normal yg
berperan u/ mempertahankan self tolerance sel B,
sel T atau keduanya

Terjadi krn self Ag yg dpt menimbulkan aktivasi,

proliferasi, diferensiasi sel T autoreaktif mjd
sel efektor yg menimbulkan kerusakan jaringan &
berbagai organ
 Mechanism of Autoantibody Secretion

Uptake of
autoantigen
 Self-reactive Antibodies are a
Normal Component of Immunity
Pathogenesis

7
 Examples of Organ Specific
Lungs of a
patient with
Goodpastures

Hashimotos disease
(thyroiditis) Vitiligo
Examples of Systemic Autoimmunity

SLE
 Examples of Systemic Autoimmunity
Sjogrens Syndrome
Cross-reacting Antigens
(Molecular Mimicry)
Examples of Molecular Mimicry
Rheumatic
fever is a
classic
example of
molecular
mimicry
Pathology of Autoimmune Diseases

Most of the autoimmune diseases attributed to

autoantibodies.

Disease processes and tissue damage are due

to Type II and Type III hypersensitivity
reactions.

Other autoimmune diseases have an

autoreactive T cell component.

Disease process and tissue damage due to

Type IV hypersensitivity reactions.
 Antigen Recognized by Autoantibodies in Systemic
Autoimmune Diseases

Antinuclear Localization Recognized Antigen Disease

antibodies
Anti-ss-DNA antibody ss-DNA SLE etc.
Anti-ds DNA antibody ds-DNA SLE
Anti-polyADP ribose poly ADPribose SLE
antibody
Anti-Scl-70 antibody Chromatin DNA topoimerase l SSc
Anti-centromere antibody centromere CREST
Anti-histone antibody Histone Drug induce lupus
Anti-U1RNP antibody U1RNP MCTD
Anti-Sm antibody U1, U2, U4/U6, U5 RNP SLE
Anti-U2RNP antibody U2RNP Overlap syndrome
Anti-SS-A/Ro antibody Nucleus hY1~hY5 RNP SjS etc.
Anti-SS-B/La antibody RNA polymerase III trancription
termination factor SjS
DNA polymerase auxiliary factor
Anti-PCNA antibody DNA dependent protein kinase SLE
activation factor
Type II Hypersensitivity
Autoimmune Diseases due to
Type II Hypersensitivity
Goodpastures Syndrome
Fluorescent anti-IgG staining of
a kidney biopsy of a patient with
Goodpastures syndrome
reveals deposits of
autoantibodies along the
basement membrane.

Mechanism of tissue damage

in Goodpastures Disease the
deposition of immune
complexes in the kidney
glomeruli, the activation of
complement and the
recruitment of inflammatory
cells.
Type III Hypersensitivity
Type III Hypersensitivity
Autoimmunity
Autoimmune Diseases due to
Type III Hypersensitivity
Systemic Lupus Erythematosus
Systemic lupus erythematosus (SLE) prototypical
systemic autoimmune disease.
Typically appears in females 13 to 40 years of age
ratio of female to male is 10:1.
Characterized by fever, weakness, arthritis, skin rashes,
pleurisy, and kidney dysfunction.
Patients produce autoantibodies to DNA, histones,
erythrocytes, platelets, leukocytes, and clotting factors.
Autoantibodies to erythrocytes or platelets can cause
hemolytic anemia or thrombocytopenia due to
complement-dependent cell lysis.
Immune complex deposition along the walls of small
blood vessels results in a Type III hypersensitivity
reaction causes damage to the endothelial cells,
resulting in vasculitis and glomerulonephritis.
Systemic Lupus Erythematosus
SLE
Systemic Lupus Erythematosus
 Systemic Lupus Erythematosus

Autoantibodies against Prevalence

Double stranded DNA (dsDNA) 30-90%
Single stranded DNA (ssDNA) 70-95%
Histones 50-80%
U1-nRNP 15-40%
Sm 5-30%
SS-A (Ro) 20-60%
SS-B (La) 10-20%
Cyclin I (PCNA) 3%
Ku 5-10%
Ribosomal P proteins 5-20%
Cardiolipin, -2-glycoprotein 1 20-40%
 Rheumatoid arthritis

Autoantibodies against Prevalence

Histones Rare
Single stranded DNA (ssDNA) 8%
RANA 90-95%
Rheumatoid factors 65-90%
Fillagrin (keratin) 50%
 Graves Disease
A disease associated with the overproduction of
thyroid hormones.
Production of thyroid hormones is normally tightly
regulated by thyroid stimulating hormone (TSH)
produced by the pituitary gland feedback
mechanisms downregulate TSH production if thyroid
hormone levels are high.
Patient with Graves Disease produces autoantibodies
that bind to and constitutively stimulate the TSH
receptor activates adenylate cyclase and the
overproduction of thyroid hormones.
Because the production of thyroid hormones is
unregulated in Graves Disease, the autoantibodies are
designated long-acting thyroid-stimulating (LATS)
antibodies.
Graves Disease
 Myasthenia Gravis
Myasthenia gravis is the prototypical autoimmune
disease with blocking autoantibodies.
The patient produces autoantibodies that bind to the
acetylcholine receptor on the motor end plates of
muscles.
Binding of the autoantibodies blocks the normal binding
of acetylcholine also induces complement-mediated
degradation of the receptors results in the weakening
of skeletal muscles.
Ultimately, the autoantibodies destroy the receptors
early signs of disease include drooping eyelids and the
inability to retract the corners of the mouth.
Myasthenia Gravis
Myasthenia Gravis
Type IV Hypersensitivity
Autoimmune Diseases due to
Type IV Hypersensitivity
Insulin-dependent Diabetes Mellitus
(IDDM Type I Diabetes)

Caused by an autoimmune attack on the pancreas.

The autoimmune response destroys the b-cells results in
decreased insulin production, leading to elevated levels of
blood glucose.
Islet cell destruction occurs by waves of immunological
attack.
CD8+ T cells (CTL) Initial infiltration of activated, which
destroy the islet cells by direct lysis.
A local increase in IFN-g, TNF-a and IL-1 occurs as a
consequence of the response.
The initial infiltration of CD8+ T cells and the activation of
macrophages referred to as insulitis.
Type I Diabetes
Islet of Langerhans in
normal pancreas.

Islet of Langerhans from

individual with insulin-
dependent diabetes
mellitus. Note the intense
lymphocyte infiltration into
the islet (insulitis).
Type I Diabetes
Scleroderma -CREST
 Scleroderma

CREST syndrome
Calcinosis
Raynauds

Esophageal dysmotility

Sclerodactyly

Telangiectases
 Scleroderma
Head and Neck
Manifestations
decreased mouth
opening
initial complaint 19%
 Laboratory Tests
Presence of serum anti-Scl-70 antibodies
Antinuclear antibody (ANA or FANA)
Rheumatoid Factor (RF)
Antibody to single stranded DNA (ssDNA)
Soluble interleukin 2 receptor level (sIL 2
r).