Autoimmunity

Definition
 Basically means immunity to self
 A condition that occurs when the
immune system mistakenly attacks
and destroys healthy body tissue.
 Failure of immune tolerance
 Autoimmunity Desease (AD)
Classification
organ-specific
 Type I diabetes mellitus
 Goodpasture’s syndrome
 Multiple Sclerosis (MS)
 Hashimoto’s thyroiditis
 Autoimmune haemoliticus
anemia
 Vitiligo
 Myasthenia gravis
 etc
Systemic
 Rheumatoid arthritis
 Schleroderma
 Systemic lupus erythematosus
(SLE)
 Primary Sjogren’n syndrome
 Polymiositis/dermatomiositis
 etc
 Examples of Organ Specific
Lungs of a
patient with
Goodpasture’s

Hashimoto’s disease
(thyroiditis) Vitiligo
Examples of Systemic Autoimmunity

SLE
 Examples of Systemic Autoimmunity
Sjogren’s Syndrome

Symptons – dry mouth, dry eyes

Causes of Autoimmunity
 GENETIC FACTORS

Multiple genes determine susceptibility to

AD

These genes related to :

 Immunoglobulin
 T-cell reseptor
 MHC (major histocompatibility complex)
 EXAMPLES OF GENE DEFECTS
 Multiple sclerosis – particular alleles of HLA-DR
(DRB1*1501, DRB5*0101)
 Systemic lupus – HLA DR3, lack of C1q and C4
 Mutation (usually deletion) of autoimmune
regulator-1 gene (AIRE-1)
 RA, DM type I – HLA DR4

Note : HLA (Human Leukocyte Antigen) = MHC

 ENVIRONMENTAL FACTORS

 Virus clustering (RA, Sjögren’s s., SLE, MS)

 Infectious microorganisms (molecular
mimicry)
 Sun exposure (SLE)
 Exogenous estrogens, sex hormones in
general
Pathogens
Rheumatic
fever is a
classic
example of
molecular
mimicry
Estrogens and Autoimmunity
 Sex
differences in
autoimmunity

Nature Immunology 2, 777 -

780 (2001)
 IMMUNE REGULATION FACTORS
A defect in any arm of the immune system can trigger
autoimmunity

Complement

T cells B cells
 animasi
 T cell dependent Antigens
 MECHANISMS OF BREAKING OF
SELF-TOLERANCE
 Disruption of cell or tissue barrier

 Infection of antigen presenting cell (T-cell B-cell

diiscordance)

 Binding of pathogen to self antigen

 Molecular mimicry

 Superantigen (T-cell bypass)

 Complement Deficiencies

 Deficiencies in the
classical complement
pathway renders more
likely to develop immune
complex diseases
 SLE
 RA
 B or T?
Autoimmunity is hard to classify as strictly a
B cell or T cell mediated disease as
multiple arms of the immune system are
involved
 Myasthenia Gravis

Disease marked by progressive weakness

and loss of muscle control
Classified as a “B cell” Disease
Autoantibodies against nicotinic
acetylcholine receptors
 Diabetes
Disease in
which the
body does not
produce or
properly use
insulin
“ T cell” Disease
T cells attack
and destroy
pancreatic
beta cells
 Multiple Sclerosis

MS patients can have autoantibodies and/or self reactive T

cells which are responsible for the demyelination
 Treatment

The key to treating

autoimmunity is
immunomodulation
 Treatment Options
• Anti-inflammatory drugs
• NSAIDS, Corticosteroids
• Immunosuppressant drugs
• Methotrexate
• Cyclofosfamid
• azatioprin
• Radiation
• Plasmapheresis
• Cell Blocking Reagents
• B cell depleting agent (Rituximab)
• Cytokine Blocking Reagents
• Antagonist TNFa (Etanercept)
• Anti IL-6 receptor (Tocilizumab)
Also palliative treatments :
 Hormone replacement in Hashimoto’s
thyroitidis and Type I DM
 Antibody THERAPY:

1. Monoclonal antibodies vs.T cells -CD2,

CD3, CD4
2. Antibodies vs. CD28, CD40L
(modulation of T cell – APC
interaction)
3. Antibodies vs. cell adhesion molecules
(VLA-4, ICAM-1) and chemokines
4. Intravenous infusion of immunoglobulin
(IVIG)
 Future THERAPY
(SELF-ANTIGEN SPECIFIC)
1. Antibodies vs. autoreactive TCR
2. Vaccine containing autoreactive TCR
3. Administration of peptides – TCR
antagonists
4. Parenteral infusion of autoantigen or cDNA
5. Oral administration of autoantigen
Comment:
all above are at the stage of experiment