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Robbins 06: Diseases of Immunity
Terms in this set (63)
(B) This young woman has a classic picture of systemic lupus erythematosus (SLE)—facial skin rash that is worsened by sunlight and renal failure with proteinuria and hematuria from immune complex deposition in the glomeruli. Defective clearance and hence increased burden of nuclear apoptotic bodies is considered a fundamental mechanism that underlies SLE. This along with loss of self-tolerance to nuclear antigens gives rise to the pathogenic DNA-anti DNA immune complexes. Activation of TH17 cells occurs in many other immunologic disorders such as inflammatory bowel disease. IFN-γ is a product of CD4+ T cells and NK cells. There is no evidence of delayed hypersensitivity or NK cell dysfunction in SLE. Molecular mimicry occurs when a microbial antigen cross-reacts with a normal tissue as in rheumatic fever. Widespread and non-specific activation of T cells by superantigens occurs in toxic shock syndrome. BP7 132-136 BP8 139-144 PBD7 231-233 PBD8 215-218
A 25-year-old woman has had increasing malaise, a skin rash of her face exacerbated by sunlight exposure, and arthralgias and myalgias for the past month. On physical examination she has mild pedal edema. On auscultation, a friction rub is audible over the chest. Laboratory findings include pancytopenia and serum creatinine 3 mg/dL. Urinalysis shows hematuria and proteinuria. A serologic test for syphilis yields a false-positive result. A renal biopsy shows a slight increase in mesangial cells and granular deposits of IgG and complement in the mesangium and along the basement membrane. Which of the following mechanisms is most likely involved in the pathogenesis of her disease?
(A) Activation of TH17 cells
(B) Defective clearance of apoptotic nuclei
(C) Increased production of IFN-γ
(D) Molecular mimicry
(E) Superantigen activation of T cells
(B) This patient has clinical and serologic features of systemic lupus erythematosus (SLE). She also has a false-positive test result for syphilis, indicating the presence of anticardiolipin antibodies. These antibodies against phospholipid-protein complexes (antiphospholipid antibodies) also are called lupus anticoagulants because they interfere with in vitro clotting tests. In vivo, they are thrombogenic. Hence, these patients can have recurrent thrombosis. Lupus anticoagulants also can occur in the absence of SLE. The other listed options can occur in SLE, but they are not mediated by antiphospholipid antibodies. BP7 131 BP8 139-144 PBD7 228-230 PBD8 217-221
A 30-year-old woman has had fever and arthralgia for the past 2 weeks. On physical examination, she has a temperature of 37.6°C and an erythematous malar rash. Initial laboratory studies are positive for ANAs at 1 : 1600 and anti-double-stranded DNA antibodies at 1 : 3200. Serum creatinine is markedly elevated, and serum complement levels are decreased. A VDRL test for syphilis is positive, and in vitro tests of coagulation (prothrombin time and partial thromboplastin time) are prolonged. Which of the following clinical features of her illness is most likely caused by antibodies that interfere with the coagulation test?
(B) Recurrent thrombosis
(D) Renal failure
(B) Entry of HIV into cells requires binding to the CD4 molecule and coreceptor molecules, such as CCR5 and CXCR4. These HIV coreceptors are receptors for chemokines on the surface of T cells and macrophages. Mutations in genes encoding these coreceptor molecules cause individuals to be resistant to the effects of HIV infection because HIV cannot enter lymphocytes and macrophages. The other cell surface receptors are not relevant for HIV entry into cells. The p24 antigen is contained within the HIV virion and is not part of cell entry mechanisms, although its presence aids in detection of HIV infection. BP7 150-151 BP8 157-160 PBD7 248-249 PBD8 217-221
In epidemiologic studies of HIV infection and AIDS, investigators noticed that certain individuals did not develop HIV infection despite known exposure to the virus under conditions that caused HIV disease in all other individuals similarly exposed. When CD4+ lymphocytes from resistant individuals are incubated with HIV-1, they fail to become infected. Such resistance to infection by HIV is most likely caused by a mutation affecting genes for which of the following cellular components?
(A) T-cell receptor
(B) Chemokine receptor
(C) Interleukin-2 receptor
(D) CD28 receptor
(E) Fc receptor
(F) p24 antigen
(B) These are features of the hyper-IgM syndrome, which results from lack of isotype switching from IgM to other immunoglobulins. Patients are particularly susceptible to Pneumocystis and to bacterial infections. The abnormal IgM antibodies in excess can attach to circulating cells and lead to cytopenias. An absence of adenosine deaminase characterizes a form of severe combined immunodeficiency. The deletion of chromosome 22q11 is a feature of the DiGeorge anomaly, which affects T cell differentiation and maturation. HIV infection can be accompanied by opportunistic infections, particularly Pneumocystis, but abnormal immunoglobulin production generally is not seen. A lack of IgA production alone is seen with selective IgA deficiency. Mutations in the BTK gene account for Bruton agammaglobulinemia, in which levels of all immunoglobulins are reduced. BP7 146 BP8 153-154 PBD7 242-243 PBD8 232-233
A 12-year-old boy has had multiple recurrent infections for the past 10 years, including Pneumocystis carinii pneumonia, Streptococcus pneumoniae otitis media, and Pseudomonas aeruginosa urinary tract infection. On physical examination, he has a temperature of 38.5°C and pharyngeal erythema with exudate. Laboratory studies show hemoglobin, 9.1 g/dL; hematocrit, 27.6%; platelet count, 130,900/mm3; and WBC count, 3440/mm3 with 47% segmented neutrophils, 3% bands, 40% lymphocytes, and 10% monocytes. Serum immunoglobulin levels are IgG, 88 mg/dL; IgM, 721 mg/dL; and IgA, undetectable. A peripheral blood smear shows nucleated RBCs. Which of the following immunological defects is most likely to produce this disease?
(A) Absence of adenosine deaminase
(B) Abnormal CD40-CD40L interaction
(C) Deletion of chromosome 22q11
(D) HIV infection
(E) Lack of IgA production by B lymphocytes
(F) Mutation in the BTK gene
(B) This girl has experienced a systemic anaphylactic reaction from a type I hypersensitivity reaction. Epinephrine is the fastest acting agent to treat this life-threatening condition. Cyclosporine is used to minimize transplant rejection. Penicillin is an antibiotic that often induces a type I hypersensitivity reaction. Glucocorticoids can reduce immune reactions, although this occurs over days to weeks, not minutes. Methotrexate is useful in the treatment of graft-versus-host disease. BP7 112-114 BP8 122-124 PBD7 206-209 PBD8 201
Within minutes after a bee sting, a 15-year-old girl suddenly has difficulty breathing. There is marked urticaria and marked edema of the hand that was stung. Which of the following is the best pharmacologic agent to treat these signs and symptoms?
(C) This woman has systemic lupus erythematosus (SLE). Patients with SLE can develop anti-RBC antibodies, which can cause hemolytic anemia. Cytopenias, including leukopenia, thrombocytopenia, and anemia, also are common. Bronchoconstriction is a feature of bronchial asthma and can occur in allergies as a predominantly type I hypersensitivity reaction. Cerebral lymphomas are rare, but may occur in immunodeficient patients, particularly patients with AIDS. Keratoconjunctivitis can be seen in Sjögren syndrome as a result of decreased tear production from lacrimal gland inflammation. Sacroiliitis is a feature of many of the spondyloarthropathies, such as ankylosing spondylitis. Sclerodactyly is seen in scleroderma. When extensive, it is usually part of the spectrum of findings associated with diffuse scleroderma; when it involves only a few areas of the skin (e.g., just the hands), it is more likely to indicate limited scleroderma (CREST syndrome). BP7 131 BP8 139-144 PBD7 231-234 PBD8 217
A 31-year-old woman notices that when she is outside in the sun for more than 1 hour, she develops a rash on her face. Laboratory studies show hemoglobin, 10.9 g/dL; hematocrit, 32.9%; platelet count, 156,800/mm3; and WBC count, 4211/mm3. Urinalysis shows no blood or glucose; there is 3+ proteinuria. The ANA test result is positive with a titer of 1 : 2048 and a diffuse homogeneous immunofluorescent staining pattern. Which of the following complications is most characteristic of her illness?
(B) Cerebral lymphoma
(C) Hemolytic anemia
(C) This woman has Sjögren syndrome, which is characterized by immunologically mediated destruction of salivary and lacrimal glands and other exocrine glands lining the respiratory and gastrointestinal tracts. Dryness and crusting of the nose can lead to perforation of the nasal septum. In 25% of cases, extraglandular tissues, such as lung, skin, kidney, and muscles, may be involved. Renal failure is more likely to occur with systemic lupus erythematosus (SLE) from glomerulonephritis. Libman-Sacks endocarditis is most often a feature of SLE. Photosensitivity is a feature of SLE, with formation of an erythematous rash in sun-exposed areas; it also can be a drug reaction. Sclerodactyly is a feature of scleroderma. When not extensive, it typically indicates limited scleroderma (CREST syndrome); when extensive, it indicates diffuse scleroderma, which has a poorer prognosis. Subcutaneous nodules can occur in rheumatic fever as part of the immunological reaction after some group A beta-hemolytic streptococcal infections. Nongonococcal urethritis is seen in Reiter syndrome, along with conjunctivitis and arthritis. BP7 139-140 BP8 148 PBD7 235-236 PBD8 221-223
A 43-year-old woman has been bothered by a chronic, dry cough for the past 5 years. She has had increasing difficulty with blurred vision for the past year. On physical examination, she has a perforated nasal septum, bilateral mild corneal scarring, and oral cavity fissuring of the tongue and corners of her mouth. Laboratory studies show antibodies to SS-A and SS-B. The serum creatinine is 2.5 mg/dL, and the urea nitrogen is 25 mg/dL. A renal biopsy specimen examined microscopically shows tubulointerstitial nephritis. Which of the following is the most serious condition likely to complicate the course of her disease?
(A) Chronic renal failure
(C) Non-Hodgkin lymphoma
(F) Subcutaneous nodules
(B) This man has a selective (isolated) IgA deficiency. Such individuals are bothered by minor recurrent sinopulmonary infections and by diarrhea. Pneumocystis infections are seen in patients with more severe acquired or inherited immunodeficiency disorders, particularly patients with AIDS, which affect cell-mediated immunity. Hepatitis infections are not directly related to immunodeficiency states, although AIDS patients with a history of injection drug use are often infected with hepatitis B or C. Resistance against fungal and viral infection is mediated by T cells. BP7 146 BP8 153-154 PBD7 242 PBD8 233
A 48-year-old man has been healthy all of his life, bothered only by an occasional mild diarrheal illness. On physical examination, his temperature is 37.1°C, and blood pressure is 125/85 mm Hg. Laboratory studies show a total WBC count of 6900/mm3 with 72% segmented neutrophils, 3% bands, 18% lymphocytes, and 7% monocytes. Serum immunoglobulin levels are IgG, 1.9 g/dL; IgM, 0.3 g/dL; and IgA, 0.01 g/dL. The ANA test result is negative. The skin test result for mumps and Candida antigens is positive. This patient is at greatest risk of infection from which of the following agents?
(A) Pneumocystis carinii
(B) Streptococcus pneumoniae
(C) Hepatitis B virus
(D) Aspergillus flavus
(E) Herpes simplex virus
(D) This patient has AIDS, with Kaposi sarcoma of the skin. Kaposi sarcoma is associated with a herpesvirus agent that is sexually transmitted: human herpesvirus 8 (HHV-8), also called the Kaposi sarcoma herpesvirus. Other herpesviruses are not involved in the pathogenesis of Kaposi sarcoma, although infection with these viruses can occur frequently in individuals with AIDS. HIV, although present in the lymphocytes and monocytes, is not detected in the spindle cells that proliferate in Kaposi sarcoma. With the exception of varicella-zoster virus, which is associated with dermatomally distributed skin vesicles known as shingles, skin lesions are uncommon manifestations of herpesviruses, which include cytomegalovirus, Epstein-Barr virus, and adenovirus. BP7 156-157 BP8 164-165 PBD7 256-257 PBD8 246-247
A 37-year-old man who is HIV-positive has noticed multiple 0.5- to 1.2-cm plaquelike, reddish purple skin lesions on his face, trunk, and extremities. Some of the larger lesions appear to be nodular. These lesions have appeared over the past 6 months and have slowly enlarged. Molecular analysis of the spindle cells found in these skin lesions is likely to reveal the genome of which of the following viruses?
(B) Epstein-Barr virus
(D) Human herpesvirus-8
(A) CD4+ cells of the TH2 type are essential to the induction of type I hypersensitivity because they can secrete cytokines, such as interleukin (IL)-4, IL-5, IL-3, and granulocyte-macrophage colony-stimulating factor, which are required for the growth, recruitment, and activation of mast cells and eosinophils. Natural killer cells can lyse other cells, such as virus-infected cells, without prior sensitization. Macrophages can secrete various cytokines, but they are not essential to type I hypersensitivity. Dendritic cells trap antigen and aid in antigen presentation. Neutrophils are recruited by cytokines to participate in acute inflammatory reactions. BP7 112-113 BP8 120-122 PBD7 206-208 PBD8 195
In an experiment, antigen is used to induce an immediate (type I) hypersensitivity response. Cytokines are secreted that are observed to stimulate IgE production by B cells, promote mast cell growth, and recruit and activate eosinophils in this response. Which of the following cells is most likely to be the source of these cytokines?
(A) CD4+ lymphocytes
(B) Natural killer cells
(D) Dendritic cells
(E) This woman has dermatomyositis, a form of inflammatory myopathy in which capillaries are the primary target for antibody and complement-mediated injury. Anti-Jo-1 antibodies, although not present in most cases, are quite specific for inflammatory myopathies. The perivascular and perimysial inflammatory infiltrates result in peripheral muscle fascicular myocyte necrosis. The process is mediated by CD4+ cells and B cells. The heliotrope rash is a characteristic feature of dermatomyositis. Anti-double-stranded DNA is specific for systemic lupus erythematosus (SLE), in which there can be myositis without significant inflammation or necrosis. Rheumatoid factor is present in most patients with rheumatoid arthritis, which is accompanied by inflammatory destruction of joints, not muscle, although muscle may atrophy secondary to diminished movement. The anti-U1-ribonucleoprotein antibodies suggest a diagnosis of mixed connective tissue disease, a condition that can overlap with polymyositis. Antihistone antibodies are associated with drug-induced SLE. BP7 143-144 BP8 151 PBD7 1342-1343 PBD8 225, 1273
For the past 6 weeks, a 52-year-old woman has had bilateral diffuse pain in her thighs and shoulders. She has difficulty rising from a chair and climbing steps. She has a rash with a violaceous color around the orbits and on the skin of her knuckles. On physical examination, she is afebrile. Muscle strength is 4/5 in all extremities. Laboratory studies show serum creatine kinase of 753 U/L, and the ANA test result is positive with a titer of 1 : 160. Which of the following tests is most specific for the diagnosis of this patient's underlying condition?
(A) Anti-double-stranded DNA antibodies
(B) Rheumatoid factor
(C) Anti-U1-ribonucleoprotein antibodies
(D) Antihistone antibodies
(E) Anti-Jo-1 antibodies
(B) The figure shows the so-called wire loop glomerular capillary lesions of lupus nephritis. Anti-Sm and anti-double-stranded DNA are specific for systemic lupus erythematosus. Anti-Sm is present in only 25% of cases, however. Scl-70 is a marker for diffuse systemic sclerosis. Jo-1 is most specific for polymyositis. HLA-B27 is seen in ankylosing spondylitis. Anticentromere antibody is seen most often with limited scleroderma. BP7 134-136 BP8 142-143 PBD7 231-233 PBD8 217-219
A 31-year-old woman has had increasing edema, chest pain, and an erythematous rash for the past 6 months. Laboratory studies show increasing serum creatinine, and urinalysis shows proteinuria with RBC casts. A renal biopsy is performed, and the light microscopic appearance of the PAS-stained specimen is shown in the figure. If present, which of the following antibodies is most helpful in diagnosing this patient's condition?
(A) This is an example of antibody directed at a parasitic infection, with Fc receptor-mediated inflammation and phagocytosis. IgG and IgE antibodies bearing Fc receptors coat the parasite. Macrophages, natural killer cells, and neutrophils can recognize the Fc receptor and destroy the antibody-coated target cells. Complement-mediated lysis is most typical of immune destruction of RBCs with hemolysis. Langhans giant cells are seen in granulomatous inflammation, a form of type IV hypersensitivity. Acute inflammatory reactions with abscess formation have little effect against tissue parasites. Leukotriene C4 is a potent agent that promotes vascular permeability and bronchial smooth muscle contraction in type I hypersensitivity reactions. BP7 115 BP8 124-125 PBD7 210 PBD8 195-196
A 23-year-old man has had myalgias and a fever for the past week. On physical examination, his temperature is 38.6°C. He has diffuse muscle tenderness, but no rashes or joint pain on movement. Laboratory studies show elevated serum creatine kinase and peripheral blood eosinophilia. Larvae of Trichinella spiralis are present within the skeletal muscle fibers of a gastrocnemius biopsy specimen. Two years later, a chest radiograph shows only a few small calcifications in the diaphragm. Which of the following immunological mechanisms most likely contributed to the destruction of the larvae?
(A) Antibody Fc receptor-mediated inflammation
(B) Complement-mediated cellular lysis
(C) Formation of Langhans giant cells
(D) Abscess formation with neutrophils
(E) Synthesis of leukotriene C4 in mast cells
(B) These findings represent chronic rejection. The progressive renal failure results from ischemic changes with vascular narrowing. Cell lysis with macrophages is typical of antibody-dependent cell-mediated cytotoxicity, which does not play a key role in chronic rejection. Granulomatous inflammation is not typical of transplant rejection. Release of leukotriene C4 from mast cells is a feature of type I hypersensitivity. Complement-mediated cell lysis can occur when antidonor antibodies are preformed in the host, as occurs in hyperacute rejection. BP7 124 BP8 131-134 PBD7 220-221 PBD8 228-229
A 45-year-old man with chronic renal failure received a kidney transplant from his brother 36 months ago. For the next 30 months, he had only minor episodes of rejection that were controlled with immunosuppressive therapy. In the past 6 months, he has had increasing serum creatinine and urea nitrogen levels. On physical examination, he is afebrile. Microscopic examination of a urinalysis specimen shows no WBCs. CT scan of the pelvis shows that the allograft is reduced in size. Which of the following immunological processes most likely accounts for these findings?
(A) Macrophage-mediated cell lysis
(B) Vascular intimal fibrosis
(C) Granulomatous vasculitis
(D) Release of leukotriene C4 from mast cells
(E) Complement-mediated cell lysis
(A) Natural killer (NK) cells have the ability to respond without prior sensitization. They carry receptors for MHC class I molecules, which inhibit their lytic function. When expression of class I MHC molecules is reduced on the cell surface, the inhibitory receptors on NK cells do not receive a negative signal, and the cell is killed. NK cells are often the first line of defense against viral infection. Neutrophils provide a nonspecific immune response, primarily to bacterial infections and not to intracellular viral infections. Macrophages can process antigen and can phagocytize necrotic cells. CD4+ cells are helper T cells that assist other cells, such as NK cells, macrophages, and B cells, in the immune response. Dendritic cells aid in antigen presentation. BP7 107 BP8 108, 113 PBD7 201-202 PBD8 188
A 20-year-old man steps into an elevator full of people who are coughing and sneezing, all of whom appear to have colds or the flu. The influenza viral particles that he inhales attach to respiratory epithelium, and viral transformation reduces the MHC class I molecules on these epithelial cells. Which of the following cells is most likely to respond to destroy the infected cells?
(A) Natural killer cell
(D) CD4 cell
(E) Dendritic cell
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