nullChapter 5:Diseases of the Immune SystemChapter 5:Diseases of the Immune SystemDepartment of Pathology
Peking Union Medical College
Lu ZhaohuiImmunity and DiseaseImmunity and DiseaseThe 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 AUTOIMMUNE DISEASES Immune reactions against self-antigens-autoimmunity result in the damage to tissues and single or mutiple organsMechanismMechanismImmunological 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 Lose of Immunological Tolerance Central Tolerance
peripheral tolerancenullnullRole of genetic factors
Role of Infections
Role of EstrogenTypes of Autoimmune DiseasesTypes of Autoimmune DiseasesOrgan / 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 DiseasesTypes of Autoimmune DiseasesSystemic or multiple organs
systemic lupus erythematosus
rheumatoid arthritis
Sjögren syndrome
Reiter syndrome
imflammatory myopathy
systemic sclerosis
polyarteritis nodosaSystemic Lupus Erythematosus, SLE Systemic Lupus Erythematosus, SLE nullSLE 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 Etiology and Pathogenesis of SLE Genetic Factors
Immunological Factors
Environmental Factors
OthersMechanisms of Tissue Injury 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) mesangial proliferative (class II) Morphology 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. MorphologyMorphologySkin.
Joints
Central Nervous System.
Pericarditis and Other Serosal Cavity Involvement
Cardiovascular system
Spleen
Lung
Other Organs and Tissues. Rheumatoid Arthritis, RA Rheumatoid Arthritis, RA nullRheumatoid 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 PathogenesisEtiology and PathogenesisGenetic susceptibility
Environmental arthritogen
Autoimmunity MorphologyMorphologyJoints
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 Rheumatoid nodules of Skin SJÖGREN SYNDROME SJÖGREN SYNDROME nullSjögren 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 PathogenesisEtiology and Pathogenesislymphocytic 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 MorphologyMorphologyLacrimal 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 Involvement of salivary gland INFLAMMATORY MYOPATHIES INFLAMMATORY MYOPATHIES nulldermatomyositis, polymyositis, and inclusion-body myositis
probably immunologically mediated SYSTEMIC SCLEROSIS SYSTEMIC SCLEROSIS nullchronic 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 Etiology and Pathogenesis progressive fibrosis
Microvascular disease MorphologyMorphologySkin
Alimentary Tract
Musculoskeletal System
Kidneys
Lungs
Heart extensive subcutaneous fibrosis extensive subcutaneous fibrosis Vasculitis Vasculitis GIANT-CELL ARTERITIS 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 MorphologyMorphology nodular intimal thickening
granulomatous inflammation
elastic lamina fragmentationGIANT-CELL ARTERITISGIANT-CELL ARTERITISPOLYARTERITIS NODOSA POLYARTERITIS NODOSA Polyarteritis nodosa (PAN) is a systemic vasculitis of small or medium-sized muscular arteries
typically involving renal and visceral vesselsMorphology. 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 NODOSAPOLYARTERITIS NODOSATHROMBOANGIITIS OBLITERANS 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 PathogenesisPathogenesisThe strong relationship to cigarette smokingMorphology Morphology sharply segmental acute and chronic vasculitis of medium-sized and small arteries
microabscesses WEGENER GRANULOMATOSIS WEGENER GRANULOMATOSIS Acute necrotizing granulomas of the upper respiratory tract
Necrotizing or granulomatous vasculitis affecting small to medium-sized vessels
Renal diseaseMorphology. Morphology. Upper respiratory tract lesions
granulomas with geographic patterns of central necrosis
vasculitis
renal lesions Rejection of Tissue Transplants Rejection of Tissue Transplants Mechanisms of Recognition and Rejection of Allografts Mechanisms of Recognition and Rejection of Allografts T Cell-Mediated Reactions
Antibody-Mediated Reactions Rejection of Solid organ transplantation (Kidney)Rejection of Solid organ transplantation (Kidney)Hyperacute Rejection.
Acute Rejection.
Acute cellular rejection
Acute humoral rejection (rejection vasculitis)
Chronic Rejection. Acute rejection of liver transplantationAcute rejection of liver transplantationTransplantation of Hematopoietic Cells 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 Immunodeficiency Syndromes nullprimary immunodeficiency disorders, always genetically determined
secondary immunodeficiency states, which may arise as complications of various diseases , ect. Infection of virus
primary immunodeficiency
Very rareACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS) ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS) Caused by the retrovirus human immunodeficiency virus (HIV)
Profound immunosuppression
Opportunistic infections
Secondary neoplasms
Neurologic manifestations. Epidemiology Epidemiology Homosexual or bisexual men
Intravenous drug abusers
Hemophiliacs
Recipients of blood and blood components
Heterosexual contacts
Parenteral transmission
5% can not be determinedEtiology:Etiology:Structure of HIV Pathogenesis of HIV Infection and AIDS Pathogenesis of HIV Infection and AIDS Clinical FeatureClinical FeatureDeletion of CD4+ lmyphocytes
Opportunistic Infections
pneumonia Pneumocystis jiroveci
Candidiasis
Cytomegalovirus
atypical mycobacteria
M. tuberculosis
Cryptococcosis
Infection of TB in an AIDS lymph nodeInfection of TB in an AIDS lymph nodeTumors Tumors Kaposi Sarcoma
AIDS-related lymphomas
Central Nervous System Disease
Clinical Course and Drug therapy of AIDSClinical Course and Drug therapy of AIDShighly active antiretroviral therapy
combination antiretroviral therapy
Acute stage
Chronic stage
Risky stage