1. AUTOIMMUNITY

2. Autoimmunity Breaking of self tolerance Both B and T cells may be involved (however, most are antibody mediated)

3. Etiology of autoimmunity disease Exact etiology, not known Suggestions: 1. Sequestered antigen Lymphoid cells may not be exposed to some self antigens during their differentiation -may be late-developing antigens or may be confined to immunologically privilleged sites ( e.g., testes, brain, eye, etc.). Release of Ag - accidental traumatic injury/r surgery. E.g. – Aspermatogenesis, endopthalmitis, encephalitis

4. 2.Escape of auto-reactive clones Negative selection (thymus) may not be fully functional to eliminate self reactive cells. Not all self antigens may be represented in the thymus or certain antigens may not be properly processed and presented.

5. 3. Loss of suppressor cells 4. Cross reactive antigens (pathogens) Antigens on certain pathogens may have determinants which cross react with self antigens and an immune response against these determinants may lead to effector cell or antibodies against tissue antigens. – molecular mimicry concept. Post streptococcal nephritis, anticardiolipin antibodies during syphilis are examples of such cross reactivity. Also rheumatic heart fever (M protein of Strep. Pyogenes and cardiac myosin

6. 5. Altered self antigens (chemical and viral infections) Drugs can bind to normal protein and make it immunogenic. E.g. Procainamide – induced systemic lupus

7. Classification of Autoimmune diseases Organ specific There are those that involve only one type of cell or organ and those involving multiple organs (systemic diseases)

8. One type of cell or organ 1.Allergic encephalitis May result following vaccination (rabbies, measles, influenza) or following infection with viral diseases (measles, influenza) Most important cause is rabbies vaccine (made in rabbit brain) When injected into human, immune response against rabbit myelin protein cross reacts with human myelin

9. 2. Chronic thyroiditis Those with Hashimoto’s chronic thyroiditis have antibodies to thyroglobulin – inflammatory process may lead to fibrosis of gland

10. Autoimmune – involving multiple organs (Systemic) 1.Systemic lupus erythematosus (SLE) Autoantibodies are formed against DNA, histones, nucleolar proteins and other components of the cell nucleus Women (20 – 60 yrs are more affected_ HLA-DR2 or –DR3 linked predisposition Drugs (Procainamide, hydralazine) – linked

11. With SLE – it is mostly due to immune complex formation – trigger complement – damages tissues Diagnosis detection of antinuclear antibodies (ANA) Treatment depends on severity of condition and organ affected – aspirin, non-steroidal anti- inflammatory drugs or corticosteroids are used

12. 2. Rheumatoid Arthritis (RA) Autoantibodies (IgM) also known as rheumatoid factor are formed against IgG Immune complexes formed are deposited small joints of hands, feet and other organs such as pleura, pericardium, skin Immune complexes trigger the complement – damage of tissue

13. 3. Rheumatic fever – affect cardiac muscle and joint tissue 4. Reiter’s syndrome (triad – arthritis, conjuctivitis & urethritis). No clear link of disease has been established BUT infection with Shigella, Salmonella, Yersinia, Campylobacter & Chlamydia Most affected are Men who are HLA-B27

14. Most important step in production of autoimmune diseases is Activation of self reactive helper (CD4) T cells These cells (Th1 and Th2) may induce either cell mediated or antibody mediated autoimmunity

15. Predisposing factors Certain HLA types have been linked to autoimmunity Since HLA types are inherited – there is genetic predisposition to autoimmune diseases

16. Diagnosis Diagnosis of autoimmune diseases is based on symptoms and detection of antibodies and/or T cells reactive against antigens of tissues and cells involved. Antibodies against cell/tissue associated antigens are detected by immunofluorescence. Antibodies against soluble antigens are normally detected ELISA or radioimmunoassay

17. Treatment Aim is to reduce patient’s immune response Anti-inflammatory (corticosteroid) and immunosuppressive (cyclosporin) drug therapy is the present method of treating autoimmune diseases.

18. Haemolytic anaemias, Thrombocytopaenis, Granulocytopenias, Diabetes, myasthenia gravis, Guillain-Barre Syndrome, Goodpasture’s syndrome (GS)