2. Introduction
• Autoimmunity is the failure of the body’s
defence system in recognizing its own
constituent parts as self, as a result of which an
immune response is generated against its own
cells and tissues.
• Any disease that results from such an aberrant
immune response is termed an autoimmune
disease
3. Immunological Tolerance
It is the ability of the immune system to identify
the antigen as “self” and to protect it from an
immunological response
Tolerance occurs in 3 forms:
• Central Tolerance
• Peripheral Tolerance
• Induced Tolerance
4.
5. Central Tolerance
• It refers to deletion of self reactive T and B
lymphocytes during their maturation in central
lymphoid organ (Thymus and Bone Marrow)
• During the thymic maturation many self antigen
are processed and presented to the developing T
cells , and developing T cell that expresses a
receptor for such a self antigen is negatively
selected and depleted by apoptosis
6. Peripheral Tolerance
• However, many of the T cells cannot be
presented in the thymus hence T cell bearing
receptors for such antigen escape into the
periphery.
• In the periphery these T lymphocytes are
agained deactivated by 3 processes:
– Anergy
– Supression by regulatory T cells
– Apoptosis
7.
8. Development of Autoimmunity
The failure to recognise the antigen as self will
lead to development of immunological
response
The possible Etiology are:
Genetic Suseptibility
Microbial influnce
9. • Genetic susceptibility: Following evidence
support the genetic factors for the
development of autoimmunity
– Familial predisposition: greater incidence in
monozygotic twins
– Role of HLA: Several autoimmune diseases are
linked to HLA, the relative risk of association of
HLA B27 and Ankylosing spondylitis is as high as
90 to 100
10. • Tissue Injury:
A large variety of microbes have been implicated
for triggering the autoimmunity due to
following mechanism
– Molecular mimicry: Viruses and microbes such as
streptococci and klebsiella share a cross reacting
epitope with the self antigen, the responses to
such microbial antigen may attack self tissue
ex: Rheumatic heart Disease
11. • Microbial infection with tissue necrosis and
inflammation may lead to up regulation of
resting APC’s in the tissue and subsequent
breakage of anergy
• The display of tissue antigens may be altered
by infections , local tissue injury may lead to
release of self antigen autoimmune response