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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
Immunity

B Cells Mature
in Marrow

Stem Cells
of the Bone
Marrow
Released into
blood, spleen,
lymph

Identify
Antigens

B Cells Replicate
to form
Plasma cells
B Memory
Cells

Cell Mediated
Immunity

T Cells Mature
in Thymus
Macrophages
carry foreign
cells to T
Helper cells
T Helper cells (Th)
produce proteins

Release
Antibodies

Effector Tc
Cells

Secrete
Interleukins

Secrete
lymphokines

Replicate
Cytotoxic (killer)
T (Tc) Cells

Stimulates
Phagocytosis

Tm Memory
Cells

faal_imun/ikun/2006

What happens when the bodys 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

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SELF
- IMUNITAS
- HIPERSENSITIF
- SAKIT
- IMUN TOLERAN

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
Crohns disease
Graves 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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