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

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

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

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.

Lose of Immunological Tolerance Central Tolerance peripheral tolerance

Role of genetic factors Role of Infections Role of Estrogen

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

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

Systemic Lupus Erythematosus, SLE

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.

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

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.

mesangial proliferative (class II)

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.

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

Rheumatoid Arthritis, RA

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

Etiology and Pathogenesis Genetic susceptibility Environmental arthritogen Autoimmunity

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.

Rheumatoid nodules of Skin

SJ Ö GREN SYNDROME

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.

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

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

Involvement of salivary gland

INFLAMMATORY MYOPATHIES

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

SYSTEMIC SCLEROSIS

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

Etiology and Pathogenesis progressive fibrosis Microvascular disease

Morphology Skin Alimentary Tract Musculoskeletal System Kidneys Lungs Heart

extensive subcutaneous fibrosis

Vasculitis

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

Morphology nodular intimal thickening granulomatous inflammation elastic lamina fragmentation

GIANT-CELL ARTERITIS

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

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

POLYARTERITIS NODOSA

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

Pathogenesis The strong relationship to cigarette smoking

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

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

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

Rejection of Tissue Transplants

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

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

Acute rejection of liver transplantation

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

Immunodeficiency Syndromes

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

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

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

Etiology: Structure of HIV

Pathogenesis of HIV Infection and AIDS

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

Infection of TB in an AIDS lymph node

Tumors Kaposi Sarcoma AIDS-related lymphomas Central Nervous System Disease

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