Dasar2 Penyakit

Autoimmunity

Pengampu Kuliah :
Prof. Adi Koesoema Aman SpPK(KH)
Prof. Ratna Akbari Ganie SpPK(KH)
 PENYAKIT AUTOIMMUN

PENGERTIAN DASAR :
AUTOIMMUNITAS : ADALAH RESPONS IMUN
TERHADAP ANTIGEN JARINGAN SENDIRI YANG
DI SEBABKAN OLEH HILANGNYA TOLERANSI →
SECARA NORMAL TDK DAPAT MEMPERTAHAN
KAN “SELF-TOLERANCE” SEL B ATAU SEL T
ATAU KEDUA2NYA .

ANTIGEN → AUTO ANTIGEN .

ANTIBODI → AUTO ANTIBODI
 Autoimmunity Origins
Horror autotoxicus:
Literally, the horror of
self-toxicity.

A term coined by the

German immunologist
Paul Ehrlich (1854-
1915) to describe the
body's innate aversion
to immunological self-
destruction.
 History Continued

This concept of autoimmunity as the cause

of human illness is relatively new, and it
was not accepted into the mainstream of
medical thinking until the 1950s and
1960s.
 Autoimmunity
 Basically means
immunity to self

 A condition that occurs

when the immune
system mistakenly
attacks and destroys
healthy body tissue.
 people
how do you recognize them ?

each person
has a face

6
 people
how do you recognize them ?

none of the
parts of the
face is unique,
but the
combination is

7
 people
how do you recognize them ?

none of the
parts of the
code is unique,
but the
combination is

8
systemic autoimmune
diseases .
how do you recognize them ?

each autoimmune disease

has its own "face"

9
 Lupus = Autoimmunity
 Systemic and affects connective tissue
 Caused by malfunctions of:
 T-cells
 B-cells
 Complement System
 Signal Transduction
 Can be lethal or not
 Unique to each individual
 PATOGENESE .

1. Antibodi dan autoimmunitas sendiri

menimbulkan kerusakan pada
jaringan .

2. Penyakit  kerusakan jaringan

(neo-antigen)  respons immun .

3. Faktor lain  kerusakan jaringan 

autoimmunitas .
 
 
The “Immunology Definition”

Failure of immune
tolerance
Causes of Autoimmunity
 Immune Regulation
A defect in any arm of the immune system can trigger autoimmunity

Complement

T cells B cells
 Autoimmune Disease
 Self tolerance is lost
 Specific adaptive immune responses
mounted against self antigens
 Inability to eliminate antigen leads to
chronic inflammatory process
 Ehrlich termed this horror autotoxicus
 Autoimmune diseases mediated by
cytotoxic antibodies (Type II)
Syndrome Autoantigen Consequences

Autoimmune Rh blood group Destruction of red blood

hemolytic anemia antigens, I antigen cells by complement
and phagocytes,
anemia
Autoimmune Platelet integrin Abnormal bleeding
thrombocytopenic GpIIb:IIIa
pupura
Goodpasture’s Non-collagenous Glomerulonephritis,
syndrome domain of basement Pulmonary hemorrhage
membrane collagen
type IV
Pemphagus vulgaris Epidermal cadherin Blistering of skin

Acute rheumatic fever Streptococcal cell-wall Arthritis, mycocarditis,

antigens, Antibodies late scarring of heart
cross-react with cardiac valves
muscle
 Autoimmune diseases mediated by
immune complexes (Type III)

Syndrome Autoantigen Consequences

Mixed essential Rheumatoid factor IgG Systemic vasculitis

cyroglobulinemia complexes (with or
without hepatitis C
antigens)
Systemic lupus DNA, histones, Glomerulonephritis,
erythematosis ribosomes, snRNP, vasculitis, arthritis
scRNP
 Autoimmune diseases mediated by
T-cells (Type IV)
Syndrome Autoantigen Consequences

Insulin-dependent Pancreatic -cell -cell destruction

diabetes mellitus antigen

Rheumatoid arthritis Unknown synovial joint Joint inflammation and

antigen destruction

Experimental Myelin basic protein, Brain invasion by CD4 T

autoimmune proteolipid protein, cells, paralysis
encephalomyelitis myelin oligodendrocyte
(EAE), multiple glycoprotein
sclerosis
Autoimmune disease susceptibility

 Genetic predisposition
 Twin studies (Diabetes: 20%
monozygotic vs. 5% dizigotic)
 Family studies
 Association with MHC genotype
 HLA genotyping
Genetic organization of the MHC in
humans and the mouse
Detailed map of the human MHC region
 Association
between
HLA and
susceptibilit
y to
autoimmune
disease
 Population studies show association of
susceptibility to insulin-dependent diabetes mellitus
(IDDM) with HLA genotype
Family studies show strong linkage of susceptibility to insulin-
dependent diabetes mellitus (IDDM) with HLA genotype
Autoimmunity involves T cells
 Ability of a T cell to respond is determined by
MHC genotype
 It has been hypothesized that susceptibility to
an autoimmune disease is determined by
differences in the ability of allelic variants of
MHC molecules to present autoantigenic
peptides
 Alternatively, self peptides may drive the
positive selection of developing thymocytes
that are specific for particular autoantigens.
Levels of autoantigens may
drive T cell selection
 If antigens are expressed at too low
a level, they may not drive negative
intrathymic selection, but sufficient
to drive positive selection
 Insulin genes transcribed at high
level in thymus protect against
diabetes
Peripheral B-cell anergy
 Elimination of
autoreactive B
cells in germinal
centers
Several ways in which infectious
agents could break self tolerance
Association of infection with
autoimmune disease
Some body sites are immunologically
priviledged
Damage to an immunologically privileged site can
induce an autoimmune response
TERIMA KASIH