Autoimunitas & Autoimmune Disease

Autoimunitas vs penyakit autoimun Autoimunitas : autoantibodi / reaktivitas sel T Autoimunitas tidak selalu penyakit autoimun Autoimunnitas bisa :
Penyebab penyakit autoimun Akibat penyakit autoimun Tidak berhubungan tetapi ditemukan berbarengan dengan penyakit autoimun

AUTOIMMUNITY VS. AUTOIMMUNE DISEASE

Autoimmunity Existence of harmless self-reactive lymphocytes and antibodies Potentially reversible Incidence higher in older age Significance unclear, possibly physiological Autoimmune disease Dependent on genetic viral and hormonal factors Features of severe tissue damage Clinical symptoms Protracted course but usually fatal Familiar clustering

AUTOIMMUNE DISEASE KEY CONCEPTS

Recognition of autoantigens by lymphocytes is critical Tissue destruction not just autoimmune cells must be present AD involve self-reactive T cells AD induction almost always depends on triggering of autoreactive CD4+ T cells

Self Tolerance

SUCCES
FAIL

HEALTHY PERSON

AUTOIMMUNITY

AUTOIMMUNE DISEASE

Breaking self-tolerance
Damage

Environmental factors

Infection Chemical/ Drugs

Genetic factors
- HLA-type - AIRE mutations - Antigen clearance - Signaling - Costimulation - Cytokines

Immune dysregulation

Hormones

Auto immune disease

Causes of Autoimmunity
Susceptibility genes (usually multiple) Loss of tolerance ( break down of tolerance ) Triggering factors (probably environmental)

Auto reactive T cells activation

Auto reactive B cells activation

Inadequate regulatory mechanism

Pathogenesis of autoimmune diseases

Environment Hormones Stochastic factors

Autoimmunity (loss of tolerance)

Genetic factors

Critical threshold

Initiation of pathogenesis Dendritic cell

IFN? Secretion T independent Ab production Increased activity B cell
Defective priming

Autoreactive T and B cells activation

Defective Antigen presentation T cell Increased activity

Increased costimulation Cytokine help Auto Ab production

Inflammation Disease

Abnormal complement fixation Defective phagocyte activation Circulating immune complex

Increased apoptosis Defective AICD Defective cytokine production

Tissue damage

No 1 2 3 4 5

Penyakit Autoimun Rematoid artritis Hashimoto tiroiditis Multipel sklerosis Miastenia gravis SLE

Wanita : Pria 5:2 10 : 1 2:1 2:1 9:1

Patofisiologi Penyakit Autoimun

T-Sel Bypass - Sistem kekebalan tubuh yang normal memerlukan aktivasi sel B oleh sel T sebelum dapat menghasilkan antibodi dalam jumlah besar. Kebutuhan sel-T bisa di bypass seperti contoh infeksi oleh organisme yang memproduksi super antigen yang mampu memulai aktivasi poliklonal sel B

Mekanisme Autoimun
Terdapat beberapa mekanisme autoimun yaitu:
Spontan Manipulasi imunologis Manipulasi genetik

Terapi
Sulit Membutuhkan kerjasama berbagai bidang ilmu kedokteran Obat masih diteliti Perkembangan ilmu sangat pesat