1. By Delia Brett & Rhondene Wint

2. Group 13 has created this presentation with the aim of sensitising others about autoimmune diseases. Autoimmune diseases are not as rare as the name suggests, so it its important that we know about the signs/symptoms, causes, diagnoses, and treatment methods. Do Learn and Enjoy!

3. Autoimmunity is an immune reaction against self- antigens which evokes the production of humoral mediated (autoantibodies), cell mediated (self reactive T cells) or complement mediated immunity. Autoimmunity can cause serious damage and loss of function to self organs and tissues leading to autoimmune diseases. Organ specific autoimmune diseases affect tissues of

4. 5 % to 7% adult affected. Two third women. More than 40 human diseases autoimmune in origin.

5. Hashimotos Thyroiditis- The body produces autoantibodies and TDTH cells against thyroid antigens leading to enlarged thyroid gland, goitre and hyperthyroidism. Pernicious Anaemia Results from defective red blood cell maturation due to inept B12 uptake. The body produces autoantibodies against intrinsic factor which is needed for B12 transport and uptake. Symptoms: loss of appetite,

6. Pictures of Diseases

7. Autoimmune Haemolytic anaemia AHA. The body makes antibodies (IgG/IgM) against a variety of RBC antigens which results in the destruction or removal of blood cells. Drug Induced Haemolytic Anaemia. Occurs when a drug causes the bodys immune system to react against its own red blood cells. Thrombocytopenic Purpura. It is a life-threatening disorder that results from the destruction of platelets by autoantibodies. Phagocytes in the liver and spleen endocytised antibody coated platelets.

8. Goodpasture Syndrome. A rare autoimmune disease of the lungs and kidneys which involve the production of autoantibodies against basal membrane of the alveoli and glomeruli. Symptoms include kidney and pulmonary damage, glomerulonephritis, pulmonary haemorrhage. Insulin Dependent Diabetes Mellitus Type I Diabetes. This disease is caused by a directed attack on the insulinproducing cell -cells in the pancreas by antibody dependent cytotoxicity, resulting in decreased production of insulin.

9. Graves Disease. This disease arises from the binding of autoantibodies to the TSH (thyroid stimulating hormone) receptors resulting in an overproduction of thyroxine. Symptoms include bulging eyes, hyperthyroidism, increased sweating, palpitation, heat intolerance. Myasthenia Gravis. A chronic autoimmune disease resulting from faulty neuromuscular transmission. The body produces autoantibodies (IgG isotype) which bind to acetylcholine receptors in the neuromuscular junction thereby blocking Ach which is needed to stimulate muscle contraction.

10. Systemic Lupus Erythematosus- Lupus is a conditioned characterised by chronic inflammation of body tissues that affects mainly women. The body produces autoantibodies against a variety of antigens like RBC, mitochondrion, lysosomes, and other common cell organelles. The ratio of female to male patients is 10:1. It occurs more frequently in Black and Hispanic women than Caucasian women. Symptoms: erythrematosus skin rashes, glomerulinephritis,

11. Characteristic butterfly rash over the cheeks of a young girl with lupus[From L. Steinman, 1993, Sci. Am. 269(3):80.]

12. Rheumatoid Arthritis RA. RA is a chronic inflammatory disease affecting the synovial joints; mainly in middle aged women. The inflamed synovial membrane is surrounded by inflammatory cells which destroy the cartilage and bone of the joints. Symptoms are: weight loss, fever, fatigue. Multiple Sclerosis MS. This disease affects the central nervous system. It characterised by the presence of scleroses (scar tissue) in the white matter of neurons, as a result of the response autoreactive T lymphocytes. Symptoms include: motor weakness, paralysis in limbs, ataxia, urinary dysfunction, mental aberration.

13. Sceleroderma- characterised by the deposition of excess collagen in the connecting tissues which results in the thickening of the skin and gradual skin lightening. The patient develops CREST syndrome - calcinosis (excess calcium deposition), Reynaulds phenomenon (abnormal blood flow in response to stress or cold), eosophageal dysfunction (difficulty swallowing), scelerodactyl (tightening scaly skin) and telangiectasia (red spots on skin). Organs affected includes the skin, kidney, heart, lungs, GI tract, and joints. Guillian Barre Syndrome. This disease commonly occurs after an infectious disease or after vaccination. The disease arises from the antibody-mediated and T-cell mediated damage against nerve tissues

14. Autoimmunity can be induced in animals in order to carry out experiments and treatment trials with the autoimmune disease. Animal models are used to clarify possible causes, mechanisms and treatment of autoimmune diseases, as some animals develop autoimmune diseases which share significant features with that of their human counterparts.

15. pics

16. Obese strain chicken. The OS chicken has a thyroid condition in which thyroid autoantibodies spontaneously occur which results in gradual destruction of the thyroid which resembles that of Hashimotos thyroiditis in human. Experiments on OS chicken have helped to elucidate the roles of B lymphocytes and T lymphocytes in this autoimmune disease; these were found to play significant roles in the development of the disease. Non obese diabetic (NOD) mouse. NOD mouse shares key features with human insulin-dependent diabetes mellitus (IDDM). In both cases, the pancreatic -islet of the Langerhans are destroyed by lymphocytes. Experiments on NOD mouse found that T cells play the decisive role in IDDM. The experimental autoimmune encephalomyelitis rat/mouse is the model animal for multiple sclerosis. When injected with myelin basic protiens or proteolipids, the rodent

17. In essence, autoimmunity arises from defects in self- tolerance mechanisms and abnormalities in cellmediated and antibody-mediated immunity. Self-tolerance mechanism failure to produce autoantibodies against self-antigens because: 1) clonal deletion of self-reactive cells, 2) tolerance of TH and B cells to self-antigens, 3) clonal ignorance whereby selfreactive lymphocytes remain dormant.

18. Some viruses and bacterial antigens can act as poly-clonal activators that activate self-reactive B cells which leads to tissue damages and diseases. Molecular mimicry by cross-reactive microbial antigens. This describes a condition where surface antigens on microbes resemble self-antigens of the body. This results in an immune assault against the microbial antigens and the self-antigens which they resemble. Availability of sequestered (isolated) self-antigens. Antigens which have been isolated from the immune system during embryonic stages become exposed during injury or trauma. These sequestered antigens may be released and exposed to immune cells which lack self-tolerance leading to the development of an autoimmune response. Aberrant (Unusual) Expression of MHC Class II Molecules. This occurs when MHC class II proteins are expressed on non-immune cells, self-antigens presented by them will activate TH cells which in turn activate cell-mediated immunity and humoral immunity against the selfantigens

19. Currently, autoimmune responses and diseases are treated via chemotherapeutic methods and organ ablation. Organ ablation is the removal of the affected organ, in some cases followed by organ transplant. Treatments are mainly aimed at suppressing an autoimmune response with the use immunosuppressive drugs, cytotoxic drugs, plasmapheresis, and organ ablation (removal of a target organ is indispensable.)

20. Non-steroidal anti-inflammatory drugs mitigate inflammations by slowing migration of lymphocytes; Cytotoxic drugs inhibit the antigen-activated T- cells; Plasmapheresis is the exchange of the affected persons plasma containing autoantibodies with plasma containing normal antibodies.

21. Immunosuppression (e.g., prednisone, cyclosporin A) Removal of thymus (some MG patients) Plasmapheresis (remove Ab-Ag complexes) T-cell vaccination (activate suppressing T cells??) Block MHC with similar peptide anti-CD4 monoclonal Ab anti-IL2R monoclonal Ab

22. Main Thesis: Research is being done on model animals in order to develop alternative ways aimed at inducing tolerance to the specific selfantigens, or removing self-reactive B and T lymphocytes. Tolerance Induction. This is achieved by the oral administration of the self-antigen, which elicits the autoimmune response, into the body. This method attempts to reintroduce specific immunity toward self-antigens

23. Monoclonal Antibody Against Autoantigens. Monoclonal antibodies bind to cells bearing the specific antigens which leads to the blocking or destruction of the cell. However, the removal of the irritating antigen does not activate the production of autoantibodies. Blockage of MHC Molecules. Blocking peptides, which have a different amino acid sequence from the antigen, are made to bind to the antigen-binding cleft on the MHC class II molecules. This prevents MHC class II from binding to the antigens and thereby autoimmune response. Induction of T-cell suppression. In the case of the EAE mouse, the administration of low doses of MBP-specific T cells immunized the mice so that when low doses of MBP is introduced the mice did not develop encephalitis.

24. Role of MHC. MHC class II molecules are more associated with autoimmunity because MHC class II are involved in the selection and activation of TH. TH cells in turn mediate the activation humoral and cell-mediated immune responses for both normal immunity and autoimmunity. Role of TH cells in autoimmunity. Abnormalities in TH cells may lead to the production autoantibodies because TH are necessary for the production of antibodies. Role of T-cell receptors autoimmunity. T-cells obtained from patients with MS and myasthenia gravis show a preferential expression of the TCR variable gene in the self-reactive T-cells. The absence of the CTLA-4 gene which codes for CTLA-4 receptor that inhibits autoimmune response can result in fatal autoimmune response and massive tissue damage

25. The important genes that regulate the development of autoimmunity are located within MHC. MHC have got critical role in maturation of T cell & induction of IR . MHC II genes are directly responsible for auto antigen processing and presentation. The structure of Ag binding groove will determine , if specific Ag will trigger an AU response.

26. REFERENCES Kindt, Thomas. Barbara Osbourne. Richard Goldsby.Kuby Immunology. (2006).6th Edition. Pearson Education, New York. Tortora, Gerard. Berdell Funke. Christine Chase. Microbiology: An introduction. (2010). 10th Edition. Benjamin Cummings, New York. Kahn, Fahim. Elements of Immunology. (2009). First Edition. Pearson, New York.