1 Dr. Amel Eassawi Dr. Abdelrahman Mustafa

HMIM 224 L3: AUTOTOLERANCE 2

3 The student should be able to:  Define the self tolerance.  Discuss the significance of self tolerance  List 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

 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. 5

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 - drugs AUTOIMMUNITY

 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

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

 Human Physiology, Lauralee Sherwood, seventh edition.  Text book Physiology by Guyton &Hall,11 th edition.  Text book of Physiology by Linda S. Contanzo, third edition.  Physiology by Berne and Levy, sixth edition. 10