Diseases of the Immune System
Immunity and Disease
• The normal immune response is best understood in the context of defense against infectious pathogens, the classical definition of immunity.
Etiology and Pathogenesis
• Genetic susceptibility • Environmental arthritogen • Autoimmunity
Morphology
• Joints
– infiltration of synovial stroma by a dense perivascular inflammatory infiltrate
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.
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
– atrophy of the acini – fibrosis, and hyalinization
• Kidney • Lung • Skin • Central Nervous System
Involvement of salivary gland
INFLAMMATORY MYOPATHIES
• principally the temporal arteries
Morphology
• nodular intimal thickening • granulomatous inflammation • elastic lamina fragmentation
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.
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%
• dermatomyositis, polymyositis, and inclusion-body myositis
• probably immunologically mediated
SYSTEMIC SCLEROSIS
• chronic inflammation thought to be the result of autoimmunity
• 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
Lose of Immunological Tolerance
• Central Tolerance • peripheral tolerance
• Role of genetic factors • Role of Infections • Role of Estrogen
Types of Autoimmune Diseases
Rheumatoid nodules of Skin
SJÖGREN SYNDROME
• Sjögren 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.
• Genetic factors
– HLA-B8,HLA-B3,DRW52,HLA-DQA1,HLADQB1
Morphology
• Lacrimal and salivary
– periductal and perivascular lymphocytic infiltration.
– The ductal lining epithelial cells may show hyperplasia
• widespread damage to small blood vessels
• progressive interstitial and perivascular fibrosis in the skin and multiple organs
Etiology and Pathogenesis
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.
Morphologyຫໍສະໝຸດ • 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
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.