School of Biomedicine

Department of Immunology

Immunopathology: Immunological tolerance

and autoimmunity, autoimmune diseases

professor Tsogtsaikhan Sandag

 Content
• Introduction to immunological tolerance
• Introduction to autoimmunity and autoimmune
diseases
• Autoantibody
 Introduction to immunological tolerance
Immunological tolerance is an active state of
unresponsiveness the immune system to an antigen against
which a response has previously developed

• The development of this condition is due to the event that the

lymphocytes responsible for the immune response against this
antigen either lost the ability to activate, or were removed from
the body
• Antigens cause the tolerance called “tolerogens” or
“tolerogenic antigens”
• Tolerance to the self-antigens is the principle property of the
immune system.
• Loss of self-tolerance is the cause of autoimmune diseases
 Introduction to immunological tolerance
• Self-tolerance is associated with specific lymphocytes
and:
– Immunological tolerance will develop when self-aggressive
lymphocyte clones 1/ destroyed; 2/ inactivated; 3/changed their
specificity
– Immunological tolerance is antigen-specific state, or tolerance is
specific only for given antigen
– Immunological tolerance may be developed in central (central
tolerance) or in peripheral (peripheral tolerance) organs of the
immune system
Development
of the
self-tolerance
Central tolerance
Central tolerance
Peripheral tolerance
Peripheral
tolerance
Peripheral tolerance
B cell central tolerance
B cell peripheral tolerance
 Introduction to autoimmune diseases

• Autoimmune disease classified by the

localization/spread of autoantigens and divided into:
– Systemic /organ non-specific/
– Organ-specific diseases
• AI diseases have a different pathways for the tissue
damage
• AI have a chronic, progressive and self supporting
(epitope
spread) course
Conditions for
development
of AI diseases
(postulates)
 Conditions for
development of AI
diseases
(genetic susceptibility,
HLA phenotype)
Conditions for development of AI diseases (HLA
phenotype & gender)
Conditions for development of AI diseases (gender)
Conditions for development of AI diseases (genetic susceptibility,
family predisposition)
Conditions for development of AI diseases
(genetic susceptibility)
 Conditions for
development of AI
diseases
(genetic
susceptibility, non-
HLA genes)
Conditions for development of AI diseases (infection)
Conditions for development of AI diseases (infection)
AI diseases (epitope spread)
 Pathogenesis of AI diseases
(signal stimulating or blocking autoantibodies)
AI diseases (autoantibodies transfer across the placenta)
AI diseases (Autoimmune thyroiditis, stimulating
autoantibodies)
 AI diseases
(Autoimmune thyroiditis, stimulating autoantibodies)
 AI diseases
(Autoimmune thyroiditis, stimulating autoantibodies)
 AI diseases
(Myasthenia gravis, blocking autoantibodies)
 AI diseases
(Goodpasture syndrome,
cross-reacting autoantibodies)
 AI diseases
(Uveitis posterior, cross-reacting autoantibodies)
 AI diseases
(Uveitis posterior, cross-reacting autoantibodies)
AI diseases (glomerulonephritis)
 AI diseases
(gluten-sensitive enteropathy)
AI diseases (autoimmune hepatitis)
AI diseases (primary biliary cirrhosis)
AI diseases (systemic lupus erythematosus - SLE)
AI diseases (systemic lupus erythematosus - SLE)
AI diseases (Type I diabetes)
AI diseases (Type I diabetes)
AI diseases (multiple sclerosis, model of experimental
autoimmune encephalitis-EAE)
 AI diseases
(multiple
sclerosis, model
of experimental
autoimmune
encephalitis-EAE)
 AI diseases
(diagnostic
importance of
serum
autoantibodies)
 Principles of autoimmune diseases therapy

1. First attack of many autoimmune diseases is associated with

infections, especially viral infection. Involvement of infectious agents
in development of autoimmune diseases have a evidence in many
cases, however it is hypothetic for some diseases. Anyway treatment
of infection and eradication of persistent infection foci is important.
2. Disorder of immune function is principle factor for development
and exacerbation of disease. Intervention directed to normalize over
activity of immune effectory function is rational part of the therapy
3. Important pathogenesis component of AI diseases determining a
clinical course of the disease is chronic inflammation. Anti-
inflammatory therapy is also rational part of the therapy.
Thank you