Chapter 6: Diseases of the Immune System Flashcards
List different mechanisms of hypersensitivity reactions and prototypical disorders.
- Immediate (type I) hypersensitivity: anaphylaxis; allergies; bronchial asthma (atopic forms)
- Antibody-mediated (type II) hypersensitivity: autoimmune hemolytic anemia; Goodpasture syndrome
- Immune complex–mediated (type III) hypersensitivity: systemic lupus erythematosus; some forms of glomerulonephritis; serum sickness; Arthus reaction
- Cell-mediated (type IV) hypersensitivity: contact dermatitis; multiple sclerosis; type 1 diabetes; tuberculosis
List 1997 Revised Criteria for Classification of Systemic Lupus Erythematosus.
Clinical Criteria
* Acute cutaneous lupus: malar rash, photosensitivity (cutaneous lupus)
* Chronic cutaneous lupus: discoid rash (cutaneous lupus)
* Nonscarring alopecia in the absence of other causes
* Oral or nasal ulcers
* Joint disease: nonerosive synovitis involving two or more peripheral joints
* Serositis: pleuritis, pericarditis
* Renal disorder: persistent proteinuria >0.5g/24 hours, or red cell casts
* Neurologic disorder: seizures, psychosis, myelitis, or neuropathy, in the absence of offending drugs or other known causes
* Hemolytic anemia (cytopenia)
* Leukopenia or lymphopenia on two or more occasions (cytopenia)
* Thrombocytopenia in the absence of offending drugs and other conditions (cytopenia)
Immunologic Criteria
* Antinuclear antibody (ANA)
* Anti-dsDNA antibody
* Anti-Sm antibody
* Antiphospholipid antibody
* Low complement (C3, C4, or CH50)
* Direct Coombs test in the absence of clinically evident hemolytic anemia
NB: 4 of 17 criteria, including at least 1 clinical criterion and 1 immunologic criterion.
Most sensitive antibody in SLE?
ANA (95-100%)
Antibody(ies) specific for SLE?
- Anti-double-stranded DNA (anti-dsDNA)
- Anti-Smith (anti-Sm)
Antibody(ies) specific for systemic sclerosis?
- Antitopoisomerase 1 (anti-Scl-70)
- Anticentromere antibody associated with CREST syndrome
TOPOgraphical map: at large = systemic sclerosis
Centromere: Crest
Antibody(ies) specific for Sjögren syndrome?
- Anti-Ro/SS-A
- Anti-La/SS-B
Antibody(ies) specific for rheumatoid arthritis?
- Anti-CCP
CCP: Common Cold calls for Painkillers (rhume)
Mechanisms of tissue injury in SLE?
- Most of the systemic lesions are caused by immune complexes (type III hypersensitivity). DNA–anti-DNA complexes can be detected in the glomeruli and small blood vessels in animal models. Low levels of serum complement (secondary to consumption of complement proteins) and granular deposits of complement and immunoglobulins in the glomeruli further support the role of immune complex deposition. An acute necrotizing vasculitis involving capillaries, arterioles, and small arteries may be present in any tissue.
- Autoantibodies specific for red blood cells, white blood cells, and platelets opsonize these cells and promote their phagocytosis and destruction, resulting in cytopenias. These are examples of antibody-mediated (type II) hypersensitivity.
- Antiphospholipid antibody syndrome. Patients with antiphospholipid antibodies may develop venous and arterial thromboses, which may be associated with recurrent spontaneous miscarriages and focal cerebral or ocular ischemia.
- The neuropsychiatric manifestations of SLE have been attributed to antibodies that cross the blood-brain barrier and react with neurons or receptors for various neurotransmitters. Other immune factors, such as cytokines, may also be involved in the cognitive dysfunction and CNS abnormalities that are associated with SLE.
6 patterns of glomerular disease seen in SLE..?
- Minimal mesangial lupus nephritis (class I) is the least common and is characterized by immune complex deposition in the mesangium, identified by immunofluorescence and by electron microscopy, but without structural changes by light microscopy.
- Mesangial proliferative lupus nephritis (class II) is characterized by mesangial cell proliferation, often accompanied by accumulation of mesangial matrix, and granular mesangial deposits of immunoglobulin and complement without involvement of glomerular capillaries.
- Focal lupus nephritis (class III) is defined by involvement of fewer than 50% of glomeruli. The lesions may be segmental (affecting only a portion of the glomerulus) or global (involving the entire glomerulus). Affected glomeruli may exhibit swelling and proliferation of endothelial and mesangial cells, leukocyte accumulation, capillary necrosis, and hyaline thrombi. There is also often extracapillary proliferation associated with focal necrosis and crescent formation. The clinical presentation ranges from mild hematuria and proteinuria to acute renal insufficiency. Red blood cell casts in the urine are common when the disease is active. Some patients progress to diffuse glomerulonephritis. The active (or proliferative) inflammatory lesions can heal completely or lead to chronic global or segmental glomerular scarring.
- Diffuse lupus nephritis (class IV) is the most common and severe form of lupus nephritis. The lesions are similar to those in class III, but differ in extent; typically, in class IV nephritis half or more of the glomeruli are affected. As in class III, the lesions may be segmental or global and on the basis of this, it can be subclassified as Class IV segmental (IV-S) or Class IV global (IV-G). Involved glomeruli show proliferation of endothelial, mesangial, and epithelial cells, with the latter producing cellular crescents that fill Bowman’s space. Subendothelial immune complex deposits may cause circumferential thickening of the capillary wall, forming “wire loop” structures on light microscopy. Immune complexes can be readily detected by electron microscopy and immunofluorescence. Lesions may progress to scarring of glomeruli. Patients with diffuse glomerulonephritis are usually symptomatic, showing hematuria as well as proteinuria. Hypertension and mild to severe renal insufficiency are also common.
- Membranous lupus nephritis (class V) is characterized by diffuse thickening of the capillary walls due to deposition of subepithelial immune complexes, similar to idiopathic membranous nephropathy. The immune complexes are usually accompanied by increased production of basement membrane–like material. This lesion typically causes severe proteinuria or nephrotic syndrome and may occur concurrently with focal or diffuse lupus nephritis.
- Advanced sclerosing lupus nephritis (class VI) is characterized by sclerosis of more than 90% of the glomeruli and represents end-stage renal disease.
Distinguish chronic discoid lupus erythematosus from SLE.
- Skin manifestations mimicking SLE, but without the systemic manifestations (or only rarely)
- 35% ANA (+)
- Anti-dsDNA (-)
- IF similar to SLE
Distinguish drug-induced lupus erythematosus from SLE.
- Drug-induced: hydralazine, procainamide, isoniazid, and d-penicillamine, anti-TNF therapy, to name only a few
- Most associated with development of ANAs
- Variable SLE-like syndrome including arthralgias, fever, and serositis
- Renal and CNS involvement is distinctly uncommon
- Antibodies specific for double-stranded DNA are rare, but there is an extremely high frequency of antibodies specific for histones
Distinguish subacute cutaneous lupus erythematosus from chronic discoid lupus erythematosus.
- The skin rash tends to be widespread, superficial, and nonscarring
- Most patients have mild systemic symptoms consistent with SLE
- Strong association with antibodies to the SS-A antigen and with the HLA-DR3 genotype
Characteristic clinical features of Sjögren syndrome?
- Dry eyes (keratoconjunctivitis sicca)
- Dry mouth (xerostomia)
- About 5% of Sjögren patients develop marginal zone lymphoma
Most common disorders associated with secondary Sjögren syndrome?
- Rheumatoid arthritis (most common)
- SLE
- Polymyositis
- Scleroderma
- Vasculitis
- Mixed connective tissue disease
- Thyroiditis
Sjögren syndrome: histologic findings (salivary glands)?
- Periductal and perivascular lymphocytic infiltration (early)
- Lymphoid follicles with germinal centers
- Ductal epithelial cell hyperplasia with duct obstruction
- Parenchymal acinar atrophy and hyaline fibrosis
- Fat replacement (late)
Main organ systems involved in systemic sclerosis?
- Skin (most common)
- Gastrointestinal tract (intestinal malabsorption)
- Kidneys (renal failure)
- Heart (cardiac failure)
- Muscles
- Lungs (pulmonary insufficiency)
Distinguish 2 types of systemic sclerosis.
- Diffuse scleroderma: widespread skin involvement at onset, with rapid progression and early visceral involvement
- Limited scleroderma: relatively benign clinical course where skin involvement is confined to fingers, forearms, and face, and visceral involvement occurs late
Define CREST syndrome.
Some patents with limited scleroderma develop a combination of Calcinosis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasia.
Histology of skin lesions in systemic sclerosis?
- Perivascular infiltrates containing CD4+ T cells and edema
- Degeneration of collagen fibers, which become eosinophilic
- Capillaries and small arteries may show thickening of the basal lamina (progressing to hyaline thickening of their walls), endothelial cell damage, and partial occlusion
- Increasing fibrosis of the dermis
- Atrophy of the epidermis and dermal appendages
- Focal and sometimes diffuse subcutaneous calcifications, especially in patients with the CREST syndrome
- Ulceration
The term mixed connective tissue disease is used to describe a disease with clinical features that overlap with those of..?
- SLE
- Systemic sclerosis
- Polymyositis
Mixed connective tissue disease is characterized serologically by..?
…high titers of antibodies to U1 ribonucleoprotein.
Clinical features of mixed connective tissue disease?
- Synovitis of the fingers
- Raynaud phenomenon
- Myositis
- Renal involvement
NB: …which is modest and responds well to corticosteroids.
Examples of IgG4-related disease?
- Mikulicz syndrome (lacrimal gland, parotid gland, and submandibular gland)
- Küttner tumor (bilateral submandibular gland)
- Riedel thyroiditis (thyroid)
- Idiopathic retroperitoneal fibrosis
- Autoimmune pancreatitis
- Inflammatory pseudotumors of the orbit, lungs, and kidneys
List 3 classes of graft rejection.
- Hyperacute
- Acute
- Chronic
List AIDS-Defining Opportunistic Infections and Neoplasms Found in Patients With HIV Infection.
