1 / 59

AUTOIMMUNITY AND AUTOIMMUNE DISEASE

DEPARTMENT OF IMMUNOLOGY INSTITUTE FOR IMMUNOBIOLOGY. AUTOIMMUNITY AND AUTOIMMUNE DISEASE. Bo Gao, Ph.D. Email: gb1112@163.com Tel: 54237379. 2010-07-02. Contents:. Introduction. Organ-Specific Autoimmune Diseases. Systemic Autoimmune Diseases. Mechanisms of Induction. Treatment.

turi
Download Presentation

AUTOIMMUNITY AND AUTOIMMUNE DISEASE

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. DEPARTMENT OF IMMUNOLOGY INSTITUTE FOR IMMUNOBIOLOGY AUTOIMMUNITY AND AUTOIMMUNE DISEASE Bo Gao, Ph.D. Email: gb1112@163.com Tel: 54237379 2010-07-02

  2. Contents: • Introduction • Organ-Specific Autoimmune Diseases • Systemic Autoimmune Diseases • Mechanisms of Induction • Treatment

  3. Introduction

  4. Autoimmunity Origins • Horror autotoxicus: Literally, the horror of self-toxicity. A term coined by the German immunologist Paul Ehrlich (1854-1915) to describe the body's innate aversion to immunological self-destruction. Paul Ehrlich , Nobel Prize in 1908 for demonstrating production of antibody

  5. Clone selection hypothesis • Self-reactive lymphocyte were deleted during development Frank Burnet 1900--1990 Nobel Prize 1960

  6. Definition of autoimmune disease • Disease caused by failure of self-tolerance and subsequent immune responses against self antigens are called autoimmune diseases.

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

  8. Organ-Specific Autoimmune Diseases • Insulin-dependent diabetes mellitus • Multiple sclerosis • Myasthenia gravis • Graves’s disease • Hashimoto’ disease • Goodpasture’s syndrome ……

  9. Systemic Autoimmune Diseases

  10. Systemic Autoimmune Diseases • Systemic lupus Erythematosus (SLE) • Rheumatoid arthritis (RA) • Sjögren’s syndrome • Scleroderma • Dermatomyositis • Mixed connective tissue disease(MCTD) …….

  11. Induction Theories for Autoimmune Disorders

  12. 1. Ag released from hidden location (by injury or infection) Intraocular antigens Post-traumatic uveitis Sperm Orchitis after vasectomy

  13. 2. Molecular mimicry (Cross-reactions)

  14. Molecular mimicry • Definition: Determinants of infectious agent mimic a host antigen and trigger self-reactive T-cell clones to attack host tissues. • Examples: • Rheumatic fever due to group A streptococcus • SLE due to Epstein-Barr virus cross reactive with nuclear Sm antigen • Lyme artrhritis due to Borrelia burgdorferi reactive with LFA-1 (lymphocyte function antigen-1)

  15. Rheumatic fever is a classic example of molecular mimicry

  16. 3. Inappropriate expression of class II MHC • “Wrong” cells induced to express MHC Class II antigen (and act as APCs) – IDDM, Hashimoto’s • Additional signals, such as IFN-gamma IL-1 and TNF

  17. 4.Epitope spreading • Definition: Initialresponse to oneself determinant (one peptide) could expand to involve additional determinants on the same molecule as well as additional self-proteins.

  18. It explains how a response to one cryptic epitope can mature into a full-blown autoimmune response .

  19. 5. Polyclonal B cell activation by CMV, EBV, • and some G-negative bacteria • - T-cell-independent • - Large amounts of IgM produced

  20. 6.Role of Infection in Autoimmunity

  21. 7. Gene factors in autoimmunity • Multiple sclerosis – particular alleles of HLA-DR (DRB1*1501, DRB5*0101) • Systemic lupus – lack of C1q and C4 • Genetically determined low expression of given self-antigen in the thymus • Mutation (usually deletion) of autoimmune regulator-1 gene (AIRE-1)

  22. Association between HLA and susceptibility to autoimmune disease

  23. 8.Estrogens and Autoimmunity

  24. 9.Other factors favoring autoimmunity • Lymphocytes abnormalities • Cytokine Imbalance (↑IL-2 in SLE) • Disturbances of apoptosis ( Deficiencies in Fas, complement, CTLA-4) • Toxins, Drugs, Chemicals (including food), UV, Stress

  25. THERAPY OF AUTOIMMUNE DISEASES

  26. Reduce symptoms • Immunosuppression Corticosteroids, azathioprine, cyclophosamide • Removal of thymus • Plasmapheresis Short-term relief (Grave’s disease, RA, SLE)

  27. Reduce inflammation • TNF-alpha blockers (RA, Crohn’s dis., psoriasis) e.g., Enbrel, Remicade, Humira • IL-1 receptor antagonist (RA) • Ab’s against IL6R and IL-15R • Statins, shown to lower CRP (RA, MS)

  28. Block MHC with similar peptide or antibody • Anti-CD4 • Blockage of IL-12 activity

  29. T cell vaccines (against activated Ag-specific T cells) • Monoclonal antibodies against a variety of target antigens • Oral induction of tolerance (MS) • So far, efforts have been more successful in mice than humans

  30. Thank you !

  31. Insulin-dependent diabetes mellitus (IDDM) • Disease in which the body does not produce enough insulin. • It is a “ T cell” Disease. • T cells attack and destroy pancreatic beta cells.

  32. Insulin-dependent diabetes mellitus (IDDM)

  33. Insulin-dependent diabetes mellitus (IDDM)

  34. Multiple Sclerosis • Myelin sheath of nerves targeted • CNS attacked by inflammatory lesions • Starts in 20-40 yr. old people • Characterized by weakness, paralysis and ocular symptoms MS patients can have autoantibodies and/or self reactive T cells which are responsible for the demyelination

  35. Myasthenia Gravis • Disease marked by progressive weakness and loss of muscle control • Classified as a “B cell” Disease • Autoantibodies against nicotinicacetylcholine receptors • Eventually destroys it

  36. Myasthenia Gravis

  37. Graves’s disease Autoantibody mimics TSH, leads to constant thyroid stimulation

  38. Hashimoto’s thyroiditis • Th1 cells and autoantibodies specific for thyroid Ag’s  infiltration of thyroid by L, M, and PC’s  hypothyroidism • Chronic inflammation and enlargement

  39. Normal thyroid gland

  40. Hashimoto’s thyroiditis

  41. Hashimoto’s thyroiditis (From Robbins Basic Pathology ,2003)

  42. Goodpasture’s syndrome • Antibodies to membrane antigens in kidney and alveoli in lungs • Specificity – part of type IV collagen • Complement activation, cell damage, inflammation

  43. The anti-basement membrane antibody in Goodpasture’s syndrome forms an even layer on the glomerular basement membrane.

  44. Systemic Lupus Erythematosus (SLE) • Typical patient: young woman with butterfly rash • Symptoms unpredictable (relapsing/remitting) • Multisystem (skin, kidneys, joints, heart)

  45. Systemic Lupus Erythematosus (SLE) Etiology • Autoantibodies! • Antinuclear Ab present in all patients with SLE... but found in other autoimmune diseases too

  46. Systemic Lupus Erythematosus (SLE) What’s so bad about having these autoantibodies? • They cause tissue injury! • Form immune complexes • Cause destruction, phagocytosis of cells • Multisystem effects: • Kidney (renal failure) • Skin (“butterfly rash”) • CNS (focal neurologic deficits) • Joints (arthritis) • Heart (pericarditis, endocarditis)

  47. Systemic Lupus Erythematosus (SLE) prognosis • Variable! Some have few symptoms, rare patients die within months. • Most patients: relapses/remissions over many years. • Acute flare-ups controlled with steroids • 80% 10-year survival • Most common cause of death: renal failure

  48. Systemic Lupus Erythematosus (SLE) Lupus nephritis. There are two focal necrotizing lesions at 11 and 2 o’clock. (H&E stain.) (Dr. Helmut Rennke) Slide 7.24

  49. Systemic Lupus Erythematosus (SLE) Lupus nephritis, diffuse proliferative type. Note the marked increase in cellularity throughout the glomerulus. (H&E stain.) (Dr. Helmut Rennke) Slide 7.25

More Related