BLOOD AND BODY DEFENCE

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Dr. Amel Eassawi

Dr. Abdelrahman Mustafa

HMIM 224L3: AUTOTOLERANCE

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OBJECTIVES

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The student should be able to:Define the self tolerance. Discuss the significance of self toleranceList the Mechanisms Involved in Tolerance: Define the autoimmunity . Recognize the different factors that cause autoimmune disease .List autoimmune diseases examples.

Immunological tolerance

• Definition: – specific unresponsiveness to an antigen that is induced by

exposure of lymphocytes to that”)• Significance:

– All individuals are tolerant of their own antigens (self-tolerance); breakdown of self-tolerance results in autoimmunity

– Therapeutic potential: Inducing tolerance may be exploited to prevent graft rejection, treat autoimmune and allergic diseases, and prevent immune responses in gene therapy, perhaps stem cell transplantation

IMMUNE SYSTEM TOLERANCE Mechanisms Involved in Tolerance:

Clonal deletion: Elimination of certain T cell in the thymus that have specify to self antigen

Clonal anergy.:Inability to generate sensitivity to the substances expecting to be antigenic

Receptor editing:Key mechanism of B clles (modification in BCR )

Inhibition by regulatory T cells. Immunological ignorance. Immune privilege.

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Autoimmunity

• Definition: immune response against self (auto-) antigen, by implication pathologic

• General principles:– Pathogenesis: The development of autoimmunity reflects

a combination of susceptibility genes and environmental triggers (usually infections)

– Different autoimmune diseases may be systemic or organ-specific; may be caused by different types of immune reactions (antibody- or T cell-mediated)

• Problems in understanding pathogenesis of human autoimmune diseases:– Failure to identify target antigens, heterogeneous disease

manifestations, disease may present long after initiation

GENETIC

PREDISPOSITION

- MHC genes

- non MHC genes

Environmental factors

- infection

- drugsAUTOIMMUNITY

Organ-specific Autoimmune diseases

Antigens and autoimmunity restricted to specific organs in the body Type I diabetes Goodpasture’s syndrome Multiple sclerosis Grave’s disease Hashimoto’ thyroiditis Myasthenia gravis

Systemic Autoimmune Disease

Antigens and autoimmunity are distributed in many tissues (systemic) Rheumatoid arthritis Systemic lupus erythematosusa polymyositis

REFERENCES

Human Physiology, Lauralee Sherwood, seventh edition.

Text book Physiology by Guyton &Hall,11th edition.

Text book of Physiology by Linda S. Contanzo, third edition.

Physiology by Berne and Levy, sixth edition.

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