* It is a specific immunologic unresponsiveness

i.e. the absence of specific immunoresponses

to a particular antigen in a fully
immunocomptent person
* Unresponsiveness to self antigens is known as
auto tolerance
* Both B-cells and T-cells participate in tolerence
* But T-cells play the primary role

Clonaldeletion:
* The process by which T-cells acquire the
ability to distinguish self from non self,
in fetal thymus
* This involves the killing of T-cells that
react against antigens present in the
fetus at that time

* T-cell tolerance (clonal anergy):

* Some self-reactive T cells are not

killed in thymus

* Functional inactivation of surviving

self-reactive T cells

* B-cells become tolerant to self by two mechanisms:

1) Clonal deletion
Probably while B-cell precursors are in bon marrow
2) Clonal anergy
B cells in the periphery
* Tolerance in B-cells is less complete than in T-cells
* The most autoimmune diseases are mediated by
antibodies

1) Immunologic maturity of the host:

Neonates are immunologically immature and well
accept allograft that would be rejected by mature host
2) Structure and dose of antigen:
a- Simple molecules induce tolerance more readily than
complex ones

b- Very high and very low doses of antigen may result

in tolerance

3) T-cells become tolerant more readily and remain

tolerant longer than B-cells
4) The continuous presence of antigen helps to
maintain tolerance
5) Administration of immunosuppressive drugs
enhances tolerance as in transplantation

1) Organ transplantation:
Introduction of tolerance may help in prevention of
rejection
2) Tumor development:
Tolerance to tumor antigen results in growth of the
tumor without being detected by the immune
mechanisms
3) Autoimmune disorders:
Disturbance of self-tolerance results in autoimmune
disease

* Autoimmune diseases occur due to

breakdown of the mechanisms that
maintain auto tolerance
* Auto-antibodies and self reactive T-cells
are produced, resulting in tissue
damage by several mechanisms

1) Genetic predisposition:
- Familial incidence of autoimmune diseases
- Most of them appear to be associated with certain
MHC genes, specially MHC II genes

e.g. Rheumatoid arthritis is associated with DR4

Thyroditis with DR5

Multiple sclerosis with DR2
SLE with DR2/DR3
Type I diabetes with DR3/DR4
Ankylosing spondylitis with B27

Rheumatoid Arthritis

2) Exposure to infectious antigens that cross react

with self antigens

- An immune response to these antigen will result

in immune attack against self antigens
e.g. Antibodies against M protein of Streptococcus
pyogens may react with heart valves and cause

Rheumatic fever

3) Alteration of self antigens or the appearance of

new antigens under the effect of drugs, chemicals,
or viral infections
4) Hormonal influences play a role e.g. SLE affects
women 10 times more than men

* The disease may be organ specific

e.g Hashimoto thyroditis
* The disease may be systemic
e.g. SLE or rheumatoid arthritis
1) Binding of an autoantibody to host cells result
in complement fixation and tissue destruction
e.g. Haemolytic anemia (Type II hypersensitivity)

Autoimmune diseases mediated by

cytotoxic antibodies (Type II)
Syndrome

Autoantigen

Consequences

Autoimmune
hemolytic anemia

Rh blood group
antigens, I antigen

Destruction of red blood

cells by complement
and phagocytes,
anemia

Autoimmune
thrombocytopenic
pupura

Platelet integrin
GpIIb:IIIa

Abnormal bleeding

Goodpastures
syndrome

Non-collagenous
domain of basement
membrane collagen
type IV

Glomerulonephritis,
Pulmonary hemorrhage

Pemphagus vulgaris

Epidermal cadherin

Blistering of skin

Acute rheumatic fever

Streptococcal cell-wall
antigens, Antibodies
cross-react with cardiac
muscle

Arthritis, mycocarditis,
late scarring of heart
valves

2) Formation of immune complexes and their

deposition in tissues, joints, kidney and skin
The immune complexes fix complement resulting in
tissue damage
e.g. SLE and rheumatoid arthritis (Type III hyper.)
3) DTH reactions (Type IV)) due to auto reactive T-cells
e.g. Ulcerative colitis, multiple sclerosis and
type I diabetes

Autoimmune diseases mediated by

immune complexes (Type III)
Syndrome

Autoantigen

Consequences

Mixed essential
cyroglobulinemia

Rheumatoid factor IgG

complexes (with or
without hepatitis C
antigens)

Systemic vasculitis

Systemic lupus
erythematosis

DNA, histones,
ribosomes, snRNP,
scRNP

Glomerulonephritis,
vasculitis, arthritis

Autoimmune diseases mediated by

T-cells (Type IV)
Syndrome

Autoantigen

Consequences

Insulin-dependent
diabetes mellitus

Pancreatic -cell
antigen

-cell destruction

Rheumatoid arthritis Unknown synovial joint

antigen

Joint inflammation and

destruction

Experimental
autoimmune
encephalomyelitis
(EAE), multiple
sclerosis

Brain invasion by CD4 T

cells, paralysis

Myelin basic protein,

proteolipid protein,
myelin oligodendrocyte
glycoprotein

1- There is elevated serum immunoglobulins

2- Complement levels may be decreased

3- Immune complexe detected in serum or organ biopsy
4- Auto antibodies can be detected in serum
e.g. anti-nuclear, anti-smooth muscles, Rh factor
and anti-mitochondrial Ab
5- Testing for antibodies specific to particular Ag,
involved in organ specific diseases (anti-thyroid Ab)

Thanks