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26 Cards in this Set
- Front
- Back
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Where can autoantibodies be detected? What might they be a result of?
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(I) autoantibodies can be detected in a large number of normal individuals - especially the elderly.
(ii) autoantibodies may result as a secondary event following tissue damage |
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Name 3 requirements of pathologic autoimmunity
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(i) presence of an autoimmune reaction
(ii) clinical or experimental evidence that the reaction is primary and not secondary to some other cause of tissue damage (iii) absence of another well-defined cause of the disease |
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Difference between localized and systemic autoimmune disease?
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Localized- antibodies direct against single cell type or organ
systemic - antibodies directing against a broad array of antigens |
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Describe Hashimoto's disease..
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Usually occurs in women, 8:1. symptoms: hypothyroidism. family history is common, 50%. There are autoantibodies against thyroid proteins - esp to TPO and thyroglobulin.
Treatment: thyroid hormone replacement |
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how can you detect for presence of autoantibodies?
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Use pt. serum from control tissue vs. pts serum and use ELISA. Can detect the antibody with other one using fluorescence.
Can detect anti-thyroglobulin antibody. |
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How do we evaluate hypothyroidism?
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Measure T4 or TSH (front line screening test)
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What is system lupus ertyhematous (SLE)?
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Multisystem disease of autoimmune origin with autoantibodies directed against a broad array of antinuclear antibodies (ANA’s), antigens of blood elements and to phospholipid-protein complexes
2. Acute onset- febrile illness with injury to skin, joints, kidneys and serosal membranes - followed by a chronic phase of remitting and relapsing episodes. 3. Almost any organ may be involved resulting in a variable and complex clinical presentation. 4. SLE is predominately a disease of women (1:700): the female to male ratio 9:1. - the disease is more common and severe in American black women (1:245). 5. Pathogenesis - failure of regulatory mechanisms that sustains self-tolerance - resulting in the production of numerous autoantibodies which form immune complexes which, in turn, deposit in blood vessels, kidneys, connective tissues and skin (Type III hypersensitivity). |
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Name 4 categories of antinuclear antibodies (ANAs)
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(i) antibodies to DNA
(ii) antibodies to histones (iii) antibodies to non-histone protein bound to RNA (iv) antibodies to nucleolar antigens |
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Indirect Immunofluorescence (IF) test
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the patients serum (with autoantibodies) is allowed to react with nuclear antigens of a human epithelial cell line (Hep-2 cells) - a fluorescein conjugated (FITC) antiserum directed against the bound antibodies is added to serve as a marker - the FITC-ANA-Ag complex is then visualized using a fluorescent microscope
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Detection of ANA’s by indirect IF - 4 patterns
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(i) homogeneous pattern - antibodies to chromatin, histones, DNA - “generic” ANA - not specific
(ii) rim or peripheral pattern - antibodies to double stranded DNA - more specific for SLE (iii) speckled pattern - antibodies to non-DNA nuclear constituents extractable in saline - “Extractable Nuclear Antigens or ENA’s (Sm antigen, SS-A, SS-B, Scl-70) - least specific of the ANA’s (iv) nucleolar pattern - antibodies to nucleolar RNA - systemic sclerosis (scleroderma) (v) centromere pattern - CREST syndrome of scleroderma |
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Name the antibodies that are diagnositic of SLE, Sjogren's syndrome, and systemic sclerosis
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1. Anti-double standard DNA (dsDNA) and Sm antigen are diagnostic of SLE.
2. Anti-RNP (SS-A, SS-B) - Sjögren’s syndrome 3. Anti-DNA - topoisomerase I (Scl- 70) - systemic sclerosis (scleroderma). |
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What are some non-ANA antibodies in SLE?
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(i) antibodies against red cells, platelets, lymphocytes
(ii) antibodies to proteins complexed to phospholipids - present in 40-50% of patients - the proteins include - prothrombin, B2 glycoprotein I, protein S, protein C -- may interfere with in-vitro clotting tests (PTT) - thus referred to as “lupus anticoagulant” - despite “in-vitro” anticoagulant activity, patients with SLE actually have complications results from a “procoagulant” state - vascular thrombosis. |
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Describe the pathology of SLE as it is present in the skin?
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Skin : - erythematous rash over malar eminences (butterfly pattern) but may also occur on the extremities and trunk
- urticaria, bullae and maculopapular lesions - light microscopy: liquefactive degeneration of the basal layer of the epidermis - the dermis exhibits vasculitis and perivascular lymphocytic infiltrates - immunofluorescence microscopy shows deposition of immunoglobulin and complement along the dermo-epidermal junction |
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Describe manifestations of the lupus in the kidney.
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involved in 60-70% of patients by light microscopy however by EM and IF essentially all patients show some abnormality. Diagnosed using EM, where you can find immune deposits.
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How is the pericardium, heart, spleen, vasculities, and CNS affected by SLE?
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(i) Heart - non-bacterial verrucous endocarditis (Libman-Sacks) - multiple irregular warty deposits (1-3 mm) on any valve in the heart and on either surface of the leaflets
- increased incidence of coronary atheroscleroses and subsequent risk for MI (ii) Spleen - onion-skinning of penicilliary arteries - capsular thickening - follicular hyperplasia or white pulp (iii) Vasculitis may occur in any organ (iv) CNS - neuropsychiatric manifestations - see changes in small vessels (intimal proliferation due to damage to endothelial cells ). ? role of antibodies directed against a synaptic membrane protein. |
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What's the disease course and treatment of SLE?
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Variable and unpredictable
2. Flare-ups and remission for years and decades - rare acute disease may lad to death in weeks/months 3. Treatment is usually steroids and/or immunosuppressive drugs 4. 90% 5 yr; 80% 10 yr survival 5. Most common cause of death - renal failure, infections, CNS disease |
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What is the clinicopathologic complex for Sjogren syndrome?
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(i) dry eyes - keratoconjunctivitis sicca
(ii) dry mouth - xerostomia |
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What does Sjogren syndrome result from?
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- results from immunologically mediated destruction of lacrimal and salivary glands
- may be primary (“sicca” syndrome) or secondary in cases of RA, SLE, scleroderma Pathology - lymphocytic infiltration and fibrosis of lacrimal/salivary glands by CD4 + helper T cells, some B cells and plasma cells |
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Describe clinical manifestations of Sjogren's.
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(i) approximately 90% of patients are women between ages 35-45 years.
(ii) keratoconjunctivitis - blurring of vision, burning, itching of eyes (iii) xerostomia - difficulty swallowing, cracks, fissure in mouth, dry mouth (iv) extra glandular complications - synovitis, pulmonary fibrosis, peripheral neuropathy (v) Mikulicz disease (syndrome) - lacrimal and salivary enlargement regardless of cause (sarcoidosis, lymphoma, leukemia) (vi) lymphadenopathy due to follicular (B cell) hyperplasia is not unusual - can predispose to malignant lymphoma (40-fold increased risk) |
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What's a good marker for Sjogren's (serology)
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1. Anti- SSA and Anti-SSB (ANAs)
pts with high SSA also have extra-glandular disease Genetics--association w/ HLA alleles. Pathogenesis- CD4- helper cell attack on glandular tissue |
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Systemic Sclerosis (scleroderma)
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excess fibrosis throughout body. Mostly involves skin but can see it in GI, kidneys, lungs.
Due to antigen driven CD4 T cells, cytokines that stimulate fibroblasts to mak collagen. Role of endothelial injury prodcuses firbrosis and activate platelets |
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Diffuse vs. Localized sclerosis
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diffuse- widespread skin involvement, anti-DNA topoisomerase I in 28-70% pts
localized- limited to skin (CREST syndrome), anticentromere antibodies |
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Describe how systemic sclerosis affect the kidneys, lungs, and heart
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Kidneys - 2/3 of patients, most common lesion is fibrosis of blood vessel walls (arteries 150 - 500 um in diameter) - hypertension occurs in 30% of patients. Renal failure accounts for approximately 50% of deaths.
(iv) Lungs - 50% of patients with pulmonary hypertension and pulmonary fibrosis (v) Heart - pericarditis and myocardial fibrosis |
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RA, what does it effect? who does it effect?
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autoimmune disorder that attacks joints leading to destruction of articular cartilage and ankylosis (fusion) of joints.
-effects skin, blood vessels, heart, lungs, muscle. -most women more than men (3-5:1) w/ peak incidence at 20s-40s |
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Describe pathogensis of RA
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triggered by exposure of an immunogenetically susceptible host to an arthritogenic microbial antigen
- an autoimmune reaction ensues mediated by CD4+ T cells associated with the release of inflammatory mediators (TNF, IL-1, IL-6, IL-5) resulting in inflammation of the synovium, synovial hypertrophy and ultimately joint destruction - small joints are affected, especially the small bones of the hands, feet, wrist, ankles, elbows, and knees. Large joints are usually spared. - involved joints are swollen, warm, painful - progressive bouts result in marked joint deformity (radial, ulnar deviation). - about 80% of patients have autoantibodies (IgM) to the Fc portion of autologous IgG - called the rheumatoid factor (RF). - RF form immune complexes in sera, synovial fluid and synovial membranes. - Circulating immune complexes underlie most of the extra-articular manifestations of RA. - RF is not present in some patients with RA, may be present in other autoimmune conditions (without arthritis) and may be present |
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Describe how RA effects the joints, skin, and blood vessels
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Joints: initially the synovium becomes edematous, thickened and hyperplastic, forming papillary fronds. The synovium is infiltrated by a dense inflammatory infiltrate of lymphocytes (CD4+ T cells), plasma cells and macrophages. These changes are accompanied by increased synovial vascularity and fibrin deposition within the joint space. Ultimately a fibrovascular mass called a pannus grows from the synovial lining and extends over the cartilaginous cap of the joint - this pannus erodes the cartilage and eventually fuses the two opposed bones of the joint (ankylosis).
2. Skin - in approximately 25% of patients, subcutaneous nodules develop at pressure points (elbow) that represent areas of fibrinoid necrosis of collagen (? ischemic) surrounded by inflammatory cells - called rheumatoid nodules. These nodules may occur in extra-articular sites (lungs, spleen, heart). 3. Blood vessels - in some patients with severe disease - - a vasculitic syndrome may develop involving medium to small size arteries resulti |
