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AUTOIMUNITAS vs
TOLERANSI

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 Self-tolerance

Central tolerance: primary lymphoid

organs
 High concentration of self-antigens
 Clonal deletion = destruksi limfosit
 B cell mechanisms
Peripheral tolerance: peripheral
tissue
 Lymphocyte
Maturation

Antibody Mediated Cell Mediated

Immunity Immunity

Stem Cells
B Cells Mature T Cells Mature
of the Bone
in Marrow in Thymus
Marrow

Released into Macrophages

Identify carry foreign
Antigens blood, spleen,
lymph cells to T
Helper cells

B Cells Replicate T Helper cells (Th)

to form produce proteins
Plasma cells

B Memory Release Secrete Secrete

Cells Antibodies Interleukins lymphokines

Replicate Stimulates
Cytotoxic (killer) Phagocytosis
T (Tc) Cells

Effector Tc Tm Memory
Cells Cells
faal_imun/ikun/2006 4
What happens when the body’s lymphocytes
fail to recognize its own cells and tissues
as such?
 Autoimmune Diseases

Failure of autoantibodies and T cells to

recognize own cells

Autoantibodies and T cells launch attack

against own cells

Perhaps due to overactive or an

overabundance of helper T lymphocytes
 Diagnosis: Autoimmune Disease

Genetic predisposition
 coding for the variety of MHC molecules
Demographics
 most common among middle aged women
Additional viral infections
Disease specific environmental factors
Aging, stress, hormones, pregnancy
- SELF OR NOT SELF DETERMINASI

RESPON IMUN :

NOT SELF SELF

- IMUNITAS
- HIPERSENSITIF
- SAKIT
- IMUN TOLERAN

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 Autoimmunity-mechanisms

Failure of self-tolerance
Molecular mimicry
Release of sequestered antigens
Change in self-antigens
Genetic factors/MHC genes
Hormonal
 AUTOIMUNITAS DAN PENYAKIT AUTOIMUN

 DEFINISI : RESPON IMUN TERHADAP ANTIGEN SELF

 TERDAPAT AUTOANTIBODI TERHADAP ANTIGEN SELF
 RESPON AUTOIMUN
 NORMAL : TOLERANS TERHADAP SEMUA KOMPONEN2
TUBUH, PENGENALAN SELF
 PENYIMPANGAN  HORROR AUTOTOXICUS
 RESPON AUTOIMUN TIDAK SELALU MENIMBULKAN
PENYAKIT AUTOIMUN
 PENYAKIT AUTOIMUN TERJADI BILA TERJADI RESPON
IMUN TERHADAP JARINGAN SEHAT  INJURI JARINGAN
KERENA REAKSI IMUNOLOGIS THD JARINGAN SENDIRI
 PADA PENDERITA TERDAPAT AUTOANTIBODI YG
OVERLAPING
 PENYAKIT DAPAT MENGENAI ORGAN SPESIFIK ATAU
SISTEMIK (NON-ORGAN SPESIFIK)  MRPK SPEKTRUM
 PATOGENESIS AUTOIMUNITAS

HIPOTESIS:
1. SEQUESTER ANTIGEN (Ag TERASING)
TOLERANSI JARINGAN JANIN, KECUALI YG TERPISAH SCR
ANATOMIS ( LENSA, TESTIS, SSP ) BILA DEWASA TERPAPAR
INF/TRAUMA RESPON AUTOIMUN
2. FORBIDDEN CLONE
MUTASI SOMATIK LIMFOSIT YG TIDAK MENGEKSPRESIKAN
ANTIGEN NON-SELF  TETAP HIDUP  TERJADI RESPON
LIMFOSIT THD JARINGAN TUBUH KERUSAKAN
3. DEFISIENSI IMUN
HIPOAKTIF ATAU DEFISIENSI SISTIM IMUN
4. CROSS-REACTION
a. PERUBAHAN STRUKTUR ANTIGEN KARENA:
- OBAT2AN (MIS: -METHYLDOPA THD ERITROSIT)
- INFEKSI VIRUS
b. STUKTUR ANTIGEN NON-SELF = SELF ( MIS: STREPT. DG
MIOKARDIUM  DEMAM REMATIK)
MEKANISME PENYAKIT AUTOIMUN:
MULTIFAKTORIAL  GENETIK : HLA-DR4 DAN HLA-Dw4
FAKTOR LINGKUNGAN
 Antinuclear antibodies

Against proteins, nucleic acids,

nucleoproteins
3-15% population + at low titers
Detection
 Immunofluorescence (Hep2)
 ELISA
 RIA (gold standard)
 Examples of Autoimmune Diseases

Multiple sclerosis
Myasthenia gravis
Crohn’s disease
Grave’s disease
Type 1 Diabetes mellitus
Rheumatoid arthritis
Psoriasis
Scleroderma
Systemic lupus erythematosus
Lupus can be difficult to diagnose
because of it's multitude of symptoms
Women are particularly prone to lupus with 90% of sufferers
being women. American, Native American and Asian women
are the groups most prone to lupus. Lupus increases the risk
of cardiovascular problems, fatigue, migraines, arthritis,
anemia, pregnancy complications, miscarriages, kidney
disorders, lung disorders, intestinal disorder and skin
disorders. Most people suffer from more than one symptom at
a time

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Medications or substances causing
Autoimmune diseases
The following drugs, medications,
substances or toxins are some of the
possible causes of Autoimmune
diseases as a symptom

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Not all types of autoimmune disease
are the same. Although the majority are
caused by a direct attack by the
immune system against healthy body
cells, not all autoimmune diseases are
of this type. Thus, the main categories
are :

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Immune cell destruction - i.e. via
immune system T-cells attacking
normal cells and destroying them
Antibody stimulation - some
autoimmune diseases result from
antibodies stimulating receptors on
certain cells, rather than attacking
them

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Unfortunately, autoimmune diseases
remain among the most poorly
understood of any category of illness. It
is thought that hormones play a role in
inducing autoimmune diseases; some
cases suddenly improve during
pregnancy, some flare-ups occur after
delivery, while others will get worse
during pregnancy, or flare up after
menopause
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 Pollard and Kono, 2013 (BMC Medicine) :
innate immune mechanism contributing to
enviromentally induced autoimmunity

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 Vadasz et al, 2013 (BMC Medicine) :
Age-related autoimmunity

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 Roldan et al,2013 (BMC Medicine) :
autoimmune cluster in families

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