1. Autoimmunity Prof M.I.N. Matee Department of Microbiology and Immunology School of Medicine MUCHS

3. AUTOIMMMUNITY & AUTOIMMUNE DISEASES Any body protein and many carbohydrates and lipids, as well as nucleic acids are potential antigens. The body is capable of constructing T-Cell receptors (TCRs) or B-Cell receptors (BCRs) that can recognise these antigens and initiate an immune response against them.

4. Mechanisms & Causes of Autoimmunity The occurrence of autoimmune diseases indicates the presence in the body of autoreactive lymphocyte clones which can, under certain circumstances, become activated. a) Some self molecules are expressed at levels below the sensitivity threshold of lymphocytes.

5. b) Some molecules are protected by a barrier from contact with lymphocytes. c) Some epitopes are normally hidden from the immune system and tolerance towards them is not established.

6. d) Autoreactive clones made tolerant by anergization can be reactivated under some circumstances. e) Some autoreactive clones may be kept in check by regulatory mechanisms involving, for example, the suppressor T cells, and when these mechanisms fail the clones may become active.

8. Molecular Mimicry The main assumption of the molecular mimicry hypothesis is that some epitopes on foreign antigens are sufficiently similar to certain self epitopes to become target of immune response elicited by the former.

9. Uncovering of Sequestered Antigens or Cryptic epitopes An injury or infection may temporarily release molecules normally inaccessible to the immune mechanism, which can then stimulate autoimmune attack on the cell carrying them.

10. Activation of Potentially Autoreactive T-Cell clones by superantigens: Autoimmune reaction can also be triggered by superantigens, produced by some microorganisms.

11. Genetic Factors Familial associations and susceptibility of inbred mouse strains to certain autoimmune diseases indicate that the development of autoimmunity depends on genetic factors.

12. Failure of Immune Regulation Some autoimmune diseases are caused by an impairment of negative regulatory T cells (T-suppressor cells) that normally inhibit potentially autoreactive clones.

13. Causes of Tissue Damage Autoimmunity develops into a disease when components of the immune system begin to damage the body. The mechanisms of tissue damage vary according to the types of autoimmune disease.

14. Examples of Autoimmune Diseases Diseases Caused Mainly by Autoantibodies. SLE: Systemic Lupus Erythematosus, Autoantibodies produced against DNA and other nuclear components.

15. Grave’s disease (Hyperthyroidism) Autoantibodies produced against the thyroid-stimulating hormone (TSH) receptor that mimic the action of TSH and stimulate excessive production of thyroid hormones (T4, T3).

16. Hashimoto’s disease (Hypothyroidism) Autoantibodies produced against thyroid antigens such as thyroglobulin.

18. Diseases caused by autoreactive T cells Insulin-dependent diabetes mellitus. In IDDN, insulin-producing  cells of the pancreatic islets of Langerhans are destroyed by CD8+ Tc cells.

19. Rheumatoid Arthritis. The disease is probably caused by T H 1 CD4+ cells reacting with fragments of joints antigens such as collagen or a heat shock protein bound to MHC class II molecules.