1. Chapter 5 ： Diseases of the Immune System Department of Pathology Peking Union Medical College Lu Zhaohui

2. Immunity and Disease The normal immune response is best understood in the context of defense against infectious pathogens, the classical definition of immunity. Innate immunity Adaptive immunity

3. AUTOIMMUNE DISEASES Immune reactions against self- antigens-autoimmunity result in the damage to tissues and single or mutiple organs

4. Mechanism Immunological tolerance is the phenomenon of unresponsiveness to an antigen as a result of exposure of lymphocytes to that antigen. Self-tolerance refers to lack of responsiveness to an individual's own antigens, and it underlies our ability to live in harmony with our cells and tissues.

5. Lose of Immunological Tolerance Central Tolerance peripheral tolerance

7. Role of genetic factors Role of Infections Role of Estrogen

8. Types of Autoimmune Diseases Organ / Cell specific AD –Hashimoto thyroiditis –autoimmune hemolytic anemia –autoimmune atrophic gastritis of pernicious anemia –autoimmune encephalomyelitis –autoimmune orchitis –Goodpasture syndrome –autoimmune thrombocytopenia –Type Ⅰ diabetes mellitus –myasthenia gravis –Graves disease –primary biliary cirrhosis –autoimmune hepatitis –ulcerative colitis –membranous glomerulonephritis

9. Types of Autoimmune Diseases Systemic or multiple organs –systemic lupus erythematosus –rheumatoid arthritis –Sj ö gren syndrome –Reiter syndrome –imflammatory myopathy –systemic sclerosis –polyarteritis nodosa

10. Systemic Lupus Erythematosus, SLE

11. SLE is the prototype of a multisystem disease of autoimmune origin, characterized by a vast array of autoantibodies, particularly antinuclear antibodies (ANAs). Acute or insidious in its onset, it is a chronic, remitting and relapsing, often febrile illness characterized principally by injury to the skin, joints, kidney, and serosal membranes.

12. Etiology and Pathogenesis of SLE Genetic Factors Immunological Factors Environmental Factors Others

13. Mechanisms of Tissue Injury SLE is a complex disorder of multifactorial origin resulting from interactions among genetic, immunological, and environmental factors that act in concert to cause activation of helper T cells and B cells and result in the production of several species of pathogenic autoantibodies.

14. mesangial proliferative (class II)

15. Morphology Kidney –minimal mesangial (class I); –mesangial proliferative (class II); –focal proliferative (class III); –diffuse proliferative (class IV); – membranous (class V). None of these patterns is specific for lupus.

16. Morphology Skin. Joints Central Nervous System. Pericarditis and Other Serosal Cavity Involvement Cardiovascular system Spleen Lung Other Organs and Tissues.

17. Rheumatoid Arthritis, RA

18. Rheumatoid arthritis is a chronic systemic inflammatory disorder that may affect many tissues and organs- skin, blood vessels, heart, lungs, and muscles-but principally attacks the joints, producing a nonsuppurative proliferative and inflammatory synovitis that often progresses to destruction of the articular cartilage and ankylosis of the joints

19. Etiology and Pathogenesis Genetic susceptibility Environmental arthritogen Autoimmunity

20. Morphology Joints –infiltration of synovial stroma by a dense perivascular inflammatory infiltrate –increased vascularity –aggregation of organizing fibrin – accumulation of neutrophils –osteoclastic activity in underlying bone – pannus Skin. Rheumatoid nodules Blood Vessels.

21. Rheumatoid nodules of Skin

22. SJ Ö GREN SYNDROME

23. Sj ö gren syndrome is a chronic disease characterized by dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia) resulting from immunologically mediated destruction of the lacrimal and salivary glands.

24. Etiology and Pathogenesis lymphocytic infiltration and fibrosis of the lacrimal and salivary glands Autoimmune factors –RF: 75% –ANAs: 50%-80% –RNP,SS-A,SS-B: 90% Genetic factors –HLA-B8,HLA-B3,DRW52,HLA-DQA1,HLA- DQB1

25. Morphology Lacrimal and salivary –periductal and perivascular lymphocytic infiltration. –The ductal lining epithelial cells may show hyperplasia –atrophy of the acini –fibrosis, and hyalinization Kidney Lung Skin Central Nervous System

26. Involvement of salivary gland

27. INFLAMMATORY MYOPATHIES

28. dermatomyositis, polymyositis, and inclusion-body myositis probably immunologically mediated

29. SYSTEMIC SCLEROSIS

30. chronic inflammation thought to be the result of autoimmunity widespread damage to small blood vessels progressive interstitial and perivascular fibrosis in the skin and multiple organs

31. Etiology and Pathogenesis progressive fibrosis Microvascular disease

32. Morphology Skin Alimentary Tract Musculoskeletal System Kidneys Lungs Heart

33. extensive subcutaneous fibrosis

34. Vasculitis

35. GIANT-CELL ARTERITIS Giant-cell (temporal) arteritis is the most common form of vasculitis among elderly chronic, typically granulomatous inflammation of large to small-sized arteries principally the temporal arteries

36. Morphology nodular intimal thickening granulomatous inflammation elastic lamina fragmentation

37. GIANT-CELL ARTERITIS

38. POLYARTERITIS NODOSA Polyarteritis nodosa (PAN) is a systemic vasculitis of small or medium- sized muscular arteries typically involving renal and visceral vessels

39. Morphology. segmental transmural necrotizing inflammation of small to medium-sized arteries weakens the arterial wall Impaired perfusion transmural inflammation fibrinoid necrosis thickening of the vessel wall

40. POLYARTERITIS NODOSA

41. THROMBOANGIITIS OBLITERANS Thromboangiitis obliterans (Buerger disease) is a distinctive disease that often leads to vascular insufficiency segmental, thrombosing, acute and chronic inflammation of medium-sized and small arteries tibial and radial arteries

42. Pathogenesis The strong relationship to cigarette smoking

43. Morphology sharply segmental acute and chronic vasculitis of medium-sized and small arteries microabscesses

44. WEGENER GRANULOMATOSIS Acute necrotizing granulomas of the upper respiratory tract Necrotizing or granulomatous vasculitis affecting small to medium- sized vessels Renal disease

45. Morphology. Upper respiratory tract lesions granulomas with geographic patterns of central necrosis vasculitis renal lesions

46. Rejection of Tissue Transplants

47. Mechanisms of Recognition and Rejection of Allografts T Cell-Mediated Reactions Antibody-Mediated Reactions

48. Rejection of Solid organ transplantation (Kidney) Hyperacute Rejection. Acute Rejection. –Acute cellular rejection –Acute humoral rejection (rejection vasculitis) Chronic Rejection.

49. Acute rejection of liver transplantation

50. Transplantation of Hematopoietic Cells GVH disease occurs in any situation in which immunologically competent cells or their precursors are transplanted into immunologically crippled recipients, and the transferred cells recognize alloantigens in the host Acute GVH disease Chronic GVH disease

51. Immunodeficiency Syndromes

52. primary immunodeficiency disorders, always genetically determined secondary immunodeficiency states, which may arise as complications of various diseases, ect. Infection of virus primary immunodeficiency –Very rare

53. ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS) Caused by the retrovirus human immunodeficiency virus (HIV) Profound immunosuppression Opportunistic infections Secondary neoplasms Neurologic manifestations.

54. Epidemiology Homosexual or bisexual men Intravenous drug abusers Hemophiliacs Recipients of blood and blood components Heterosexual contacts Parenteral transmission 5% can not be determined

55. Etiology: Structure of HIV

56. Pathogenesis of HIV Infection and AIDS

57. Clinical Feature Deletion of CD4+ lmyphocytes Opportunistic Infections –pneumonia Pneumocystis jiroveci –Candidiasis –Cytomegalovirus –atypical mycobacteria –M. tuberculosis –Cryptococcosis

58. Infection of TB in an AIDS lymph node

59. Tumors Kaposi Sarcoma AIDS-related lymphomas Central Nervous System Disease

60. Clinical Course and Drug therapy of AIDS highly active antiretroviral therapy combination antiretroviral therapy Acute stage Chronic stage Risky stage