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