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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?
(A) Arthritis
(B) Recurrent thrombosis
(C) Rash
(D) Renal failure
(E) Fever

(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?
(A) Cyclosporine
(B) Epinephrine
(C) Penicillin
(D) Glucocorticoids
(E) Methotrexate

(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?
(A) Bronchoconstriction
(B) Cerebral lymphoma
(C) Hemolytic anemia
(D) Keratoconjunctivitis
(E) Sacroiliitis
(F) Sclerodactyly

(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
(B) Endocarditis
(C) Non-Hodgkin lymphoma
(D) Photosensitivity
(E) Sclerodactyly
(F) Subcutaneous nodules
(G) Urethritis

(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?
(A) Cytomegalovirus
(B) Epstein-Barr virus
(C) Adenovirus
(D) Human herpesvirus-8
(E) HIV-1

(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
(C) Macrophages
(D) Dendritic cells
(E) Neutrophils

(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) Scl-70
(B) Anti-Sm
(C) Jo-1
(D) Anti-HLA-B27
(E) Anticentromere

(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
(B) Neutrophil
(C) Macrophage
(D) CD4 cell
(E) Dendritic cell

(E) These findings indicate a failure of terminal differentiation of B cells into IgA-secreting plasma cells. Lack of IgA in mucosal secretions increases the risk of respiratory and gastrointestinal infections. IgA antibodies present in serum can lead to a transfusion reaction with IgA in donor serum. Individuals with severe combined immunodeficiency would not live as long as this patient with such mild infections. HIV infection is marked by failure of cell-mediated immunity. DiGeorge syndrome manifests in infancy with failure of cell-mediated immunity from lack of functional T cells. Wiskott-Aldrich syndrome is associated with eczema and thrombocytopenia. BP7 146 BP8 153-154 PBD7 242 PBD8 233

A 35-year-old man has a history of mild infections of the upper respiratory tract. He also has had diarrhea for most of his life, although not severe enough to cause malabsorption and weight loss. After an episode of trauma with blood loss, he receives a blood transfusion and has an anaphylactic reaction. Which of the following underlying conditions best explains these findings?
(A) Severe combined immunodeficiency
(B) HIV infection
(C) DiGeorge syndrome
(D) Wiskott-Aldrich syndrome
(E) Selective IgA deficiency

(C) This history is typical of the late-phase reaction in type I hypersensitivity. The initial rapid response is largely caused by degranulation of mast cells. The late-phase reaction follows without additional exposure to antigen and is characterized by more intense infiltration by inflammatory cells, such as neutrophils, eosinophils, basophils, monocytes, and CD4+ lymphocytes. There is more tissue destruction in this late phase. BP7 113-114 BP8 120-124 PBD7 206-209 PBD8 198-200

A laboratory worker who is "allergic" to fungal spores is accidentally exposed to a culture of the incriminating fungus on a Friday afternoon. Within 1 hour, he develops bouts of sneezing, watery eyes, and nasal discharge. The symptoms seem to subside within a few hours of returning home, but reappear the next morning, although the laboratory fungus is not present in his home environment. The symptoms persist through the weekend, and on Monday morning, he sees the physician. Which of the following cells is most likely to be seen on microscopic examination of the patient's nasal discharge?
(A) Mast cells and neutrophils
(B) Lymphocytes and macrophages
(C) Neutrophils, eosinophils, and CD4+ lymphocytes
(D) Neutrophils and CD8+ lymphocytes
(E) Mast cells, lymphocytes, and macrophages

(B) Macrophages can become infected with HIV and are not destroyed as CD4+ cells are. Instead, macrophages survive to carry the infection to tissues throughout the body, particularly the brain. HIV infection of the brain can result in encephalitis and dementia. Natural killer cells and neutrophils play no significant role in HIV infection. CD8+ lymphocytes cannot be infected with HIV. Langerhans cells in mucosal surfaces may aid in initial HIV infection of CD4+ lymphocytes. BP7 151-153 BP8 161-162 PBD7 252-253 PBD8 242

A 30-year-old man infected with HIV begins to have difficulty with activities of daily living. He has memory problems and decreased ability to perform functions that require fine motor control, such as writing and painting. His CD4+ lymphocyte count currently is 150/µL. Which of the following cell types is most important for the dissemination of the infection into the central nervous system?
(A) Natural killer cell
(B) Macrophage
(C) Neutrophil
(D) CD8+ lymphocyte
(E) Langerhans cell

(C) This patient has a localized immune complex reaction (Arthus reaction), which activates and depletes complement C3 and C4. IgE concentration is increased in individuals with atopy and the potential for type I hypersensitivity. Although neutrophils are being recruited locally to the inflammatory reaction in this case, they are not depleted systemically, and they may be increased in the circulation. Skin tests are measures of type IV hypersensitivity when antigens such as tuberculin are used. CD4+ lymphocytes assist in various antibody-mediated and cell-mediated immune reactions, but their numbers in peripheral blood do not change appreciably. BP7 119 BP8 120, 127-128 PBD7 215 PBD8 197, 205

A 29-year-old man has developed marked abdominal pain over the past week. On physical examination, there is diffuse abdominal tenderness with decreased bowel sounds, but no masses are noted. The stool is negative for occult blood. Laboratory studies show a serum creatinine level of 4.4 mg/dL and urea nitrogen level of 42 mg/dL. Microscopic examination of a renal biopsy specimen shows focal fibrinoid necrosis of the small arterial and arteriolar vascular media and intravascular microthrombi. Scattered neutrophils are seen in these areas of necrosis. Which of the following laboratory findings would most likely be present in this patient?
(A) Increased IgE
(B) Neutropenia
(C) Decreased complement C3
(D) Tuberculin skin test positivity
(E) CD4+ lymphocytosis

(C) In chronic inflammatory conditions such as rheumatoid arthritis, the serum amyloid-associated (SAA) precursor protein forms the major amyloid fibril protein AA. Amyloid is deposited in interstitial locations, not intracellularly. The P component is a minor component of the amyloid. All amyloid shows characteristic "apple-green" birefringence under polarized light microscopy after Congo red staining—anything else would not be amyloid. Amyloid derived from light chains in association with multiple myeloma has AL fibrils. BP7 159-160 BP8 166, 168 PBD7 260, 262 PBD8 250-253

A 63-year-old man has had chronic arthritis for the past 15 years. Physical examination shows ulnar deviation with bony ankylosis producing swan-neck deformities of the fingers. Laboratory studies show 4.2 g of protein in a 24-hour urine collection, serum creatinine of 3.1 g/dL, and urea nitrogen of 3 g/dL. A rectal biopsy is performed, which shows deposition of amorphous pink material in the mucosa. The material stains positive with Congo red. Which of the following best describes this material in the mucosa?
(A) It is within the cytoplasm
(B) It contains greater than 50% P component
(C) It is derived from an acute-phase reactant
(D) It does not show birefringence after Congo red staining
(E) It is derived from λ light chains

(B) This patient has a drug-induced systemic lupus erythematosus (SLE)-like condition. Drugs such as procainamide, hydralazine, and isoniazid can cause this condition. Test results for ANA are often positive, but test results for anti-double-stranded DNA are negative. Antihistone antibodies are present in many cases. Characteristic signs and symptoms of SLE are often lacking, and renal involvement is uncommon. Remission occurs when the patient stops taking the drug. Anti-Sm antibody shows specificity for SLE. Anti-Jo-1 antibody has specificity for polymyositis/dermatomyositis. Anti-U1-ribonucleotide protein has specificity for mixed connective tissue disease. Anticentromeric antibody is most likely to be present with limited scleroderma (CREST syndrome). Anti-SS-A antibody is most characteristic of Sjögren syndrome. BP7 131 BP8 140 PBD7 235 PBD8 221

A 60-year-old woman who undergoes a routine health screening examination has a blood pressure of 155/95 mm Hg. She receives antihypertensive therapy that includes hydralazine. Four months later, she develops arthralgias, myalgias, and a malar erythematous rash. Laboratory findings include an ANA titer of 1 : 2560 in a diffuse pattern. Anti-double-stranded DNA antibodies are not present. Which of the following autoantibodies has the greatest specificity for her condition?
(A) Anti-Sm
(B) Antihistone
(C) Anti-Jo-1
(D) Anti-U1-ribonucleoprotein
(E) Anticentromere
(F) Anti-SS-A

(F) This child has features of X-linked agammaglobulinemia of Bruton. In this condition, B cell maturation stops after the rearrangement of heavy-chain genes, and light chains are not produced. Complete immunoglobulin molecules with heavy and light chains are not assembled and transported to the cell membrane. The lack of immunoglobulins predisposes the child to recurrent bacterial infections. Because T cell function remains intact, viral, fungal, and protozoal infections are uncommon. CD4+ and CD8+ lymphocytes differentiate from precursors in the thymus, which is not affected by the BTK gene mutation that gives rise to Bruton agammaglobulinemia. Follicular dendritic cells are a form of antigen-presenting cell that is not affected by B-cell and T-cell disorders. Monocytes may leave the circulation to become tissue macrophages, a process not dependent on B cell maturation. Natural killer (NK) cells are part of the innate immune system and respond to antibody coating abnormal cells—a process diminished by reduced antibody production—but the NK cells themselves are not directly affected by lack of immunoglobulin. Lack of stem cell differentiation is incompatible with life. BP7 144-146 BP8 152-153 PBD7 240-242 PBD8 231-232

A 4-year-old boy has a history of recurrent sinopulmonary infections with Staphylococcus aureus and Streptococcus pneumoniae since age 17 months. He also developed an arthritis that cleared with immunoglobulin therapy. On physical examination, he is at the 30th percentile for height and weight. His temperature is 37.9°C. There is no lymphadenopathy, and lymph nodes are difficult to palpate. There is no hepatosplenomegaly. Laboratory studies show total serum protein of 5.1 g/dL and albumin of 4.6 g/dL. A lymph node biopsy specimen shows lymph nodes with rudimentary germinal centers. Over the next 10 years, the child develops arthralgias and erythematous skin rashes and has a positive ANA test result. Which of the following types of cells has most likely failed to differentiate to produce this patient's disease?
(A) CD4+ lymphocyte
(B) CD8+ lymphocyte
(C) Follicular dendritic cell
(D) Monocyte
(E) Natural killer cell
(F) Pre-B cell
(G) Stem cell

(C) This patient has severe combined immunodeficiency (SCID). Because the T-cell and B-cell arms of the immune system are deficient, there are severe and recurrent infections with bacteria, viruses, and fungi. With the family history of males being affected, the patient most likely has X-linked SCID. This form results from mutations in the common γ chain that is a part of many cytokine receptors, such as interleukin (IL)-2, IL-4, IL-7, and IL-15. These cytokines are needed for normal B-cell and T-cell development. The marked lymphoid hypoplasia is not typical of HIV infection. Loss of chromosome 22q11 is seen in DiGeorge syndrome. BTK gene mutations give rise to Bruton agammaglobulinemia. Mutation in the CD40 ligand is responsible for hyper-IgM syndrome. BP7 146-147 BP8 153-154 PBD7 243-244 PBD8 234-235

A 3-month-old boy has had recurrent infections of the respiratory, gastrointestinal, and urinary tracts since birth. The infectious agents have included Candida albicans, Pneumocystis carinii, Pseudomonas aeruginosa, and cytomegalovirus. Despite intensive treatment with antibiotics and antifungal drugs, he dies at age 5 months. At autopsy, lymph nodes are small with very few lymphocytes and no germinal centers. The thymus, Peyer patches, and tonsils are hypoplastic. There is a family history of other males with similar findings. Which of the following immunological alterations best describes the abnormality that caused this patient's illness?
(A) Maternal HIV infection
(B) Loss of chromosome 22q11
(C) Mutation in the common γ chain of cytokine receptors
(D) Mutation in the BTK gene
(E) Mutation in CD40 ligand

(C) This patient has features of myasthenia gravis, a form of type II hypersensitivity reaction in which antibody is directed against cell surface receptors. Antibodies to acetylcholine receptors impair the function of skeletal muscle motor end plates. Antibodies are produced by B cells, and macrophages are not a significant part of this hypersensitivity reaction; there is little or no inflammation of the muscle in myasthenia gravis. Muscle lysis by CD8+ T cells occurs in polymyositis. Immune complex-mediated injury is a feature of dermatomyositis. Delayed hypersensitivity reactions are more likely in parasitic infestations of muscles. BP7 115-116 BP8 126 PBD7 210-211 PBD8 203

A 34-year-old woman has experienced increasing muscular weakness over the past 5 months. This weakness is most pronounced in muscles that are used extensively, such as the levator palpebrae of the eyelids, causing her to have difficulty with vision by the end of the day. After a night's sleep, her symptoms have lessened. On physical examination, she is afebrile. No skin rashes are noted. Muscle strength is 5/5 initially, but diminishes with repetitive movement. Which of the following is the most likely mechanism for muscle weakness in this patient?
(A) Secretion of cytokines by activated macrophages
(B) Lysis of muscle cells by CD8+ lymphocytes
(C) Antibody-mediated dysfunction of neuromuscular junction
(D) Immune complex deposition in muscle capillaries
(E) Delayed hypersensitivity reaction against muscle antigens

(E) This patient has diffuse systemic sclerosis (scleroderma). The small arteries of the kidney are damaged by a hyperplastic arteriolosclerosis that can be complicated by very high blood pressure and renal failure. Meningitis and adrenal failure are not typical features of autoimmune diseases. Glomerulonephritis is a more typical complication of systemic lupus erythematosus. With scleroderma, the gastrointestinal tract undergoes fibrosis, without any tendency to perforation or ulceration. BP7 142-143 BP8 148-151 PBD7 237-239 PBD8 223-225

A 45-year-old woman has experienced difficulty in swallowing that has increased in severity over the past year. She also has experienced malabsorption, shown by a 5-kg weight loss in the past 6 months. She reports increasing dyspnea during this time. On physical examination, her temperature is 36.9°C, pulse is 66/min, respirations are 18/min, and blood pressure is 145/90 mm Hg. Echocardiography shows a large pericardial effusion. The ANA test result is positive at 1 : 512 with a nucleolar pattern. Which of the following serious complications of the patient's underlying autoimmune disease is most likely to occur?
(A) Meningitis
(B) Glomerulonephritis
(C) Perforated duodenal ulcer
(D) Adrenal failure
(E) Malignant hypertension

(A) This infant has DiGeorge syndrome, which can involve the thymus, parathyroids, aorta, and heart. T cell function is deficient, resulting in recurrent and multiple fungal, viral, and protozoal infections. Failure of B cell maturation to plasma cells is a mode of development of common variable immunodeficiency. Some cases of severe combined immunodeficiency are caused by lack of adenosine deaminase. HIV infection does not explain the hypocalcemia at birth. Failure of pre-B cell maturation results in Bruton agammaglobulinemia. BP7 146 BP8 153-154 PBD7 243 PBD8 234

A 30-year old woman gives birth at term to a normal-appearing infant girl. One hour after birth, the neonate exhibits tetany. On physical examination, she is at the 55th percentile for height and weight. Laboratory studies show serum calcium of 6.3 mg/dL and phosphorus of 3.5 mg/dL. Over the next year, the infant has bouts of pneumonia caused by Pneumocystis carinii and Aspergillus fumigatus and upper respiratory infections with parainfluenza virus and herpes simplex virus. Which of the following mechanisms is most likely to be responsible for the development of the clinical features seen in this infant?
(A) Malformation of third and fourth pharyngeal pouches
(B) Failure of maturation of B cells into plasma cells
(C) Lack of adenosine deaminase
(D) Acquisition of maternal HIV infection at delivery
(E) Failure of differentiation of pre-B cells into B cells

(A) The CD4+ lymphocytes are thought to respond to some unknown antigenic stimulation, releasing cytokines that activate further macrophages and mast cells. The result is extensive dermal fibrosis that produces the clinical appearance of sclerodactyly in scleroderma. Neutrophils and natural killer cells do not participate in this process. Despite scleroderma being an autoimmune disease, inflammation is minimal. The major finding is progressive fibrosis of skin, lung, and gastrointestinal tract. BP7 141-142 BP8 148-151 PBD7 237-239 PBD8 224-225

A 39-year-old woman has fingers that are tapered and clawlike, with decreased motion at the small joints. The microscopic appearance of the skin is shown in the figure. The patient also has diffuse interstitial fibrosis of the lungs, with pulmonary hypertension and cor pulmonale. Which of the following dermal inflammatory cells is the most likely initiator of the process that is the cause of her skin disease?
(A) CD4+ lymphocyte
(B) Macrophage
(C) Mast cell
(D) Neutrophil
(E) Natural killer cell

(E) This woman's original symptoms, although nonspecific, are seen in more than half of adults with acute HIV infection. The average time to development of AIDS is 8 to 10 years; onset of opportunistic infections occurs as the CD4+ cell count decreases to less than 200/µL. Spondyloarthropathies and autoimmune diseases, such as systemic lupus erythematosus or scleroderma, are unlikely to have such a long interval between illnesses, and are not as likely to manifest opportunistic infections without immunosuppressive therapy. The ANA is typical of autoimmune diseases. HLA-B27 antigen is associated with spondyloarthropathies. Anticentromere antibody is seen in limited scleroderma. Individuals with AIDS may have a polyclonal gammopathy, but not marked hypogammaglobulinemia. BP7 154-155 BP8 159 PBD7 253-254 PBD8 243-244

A 19-year-old, previously healthy woman had an acute illness with fever, myalgia, sore throat, and mild erythematous rash over the abdomen and thighs. The symptoms abated after 1 month, and she remained healthy for 8 years. Now, decreased visual acuity and pain in the right eye lead to a finding of cytomegalovirus retinitis on funduscopy. Assuming that the patient's initial illness and the ocular problem are a part of the same disease process, which of the following laboratory findings would most likely be present after her ocular problems began to appear?
(A) ANA titer 1 : 1024
(B) Total serum globulin level 650 mg/dL
(C) Positive HLA-B27 antigen
(D) Anticentromere antibody titer 1 : 512
(E) CD4+ lymphocyte count 102/µL

(A) Opportunistic infections in an intravenous drug abuser suggest a diagnosis of AIDS. The most common neoplasms seen in association with AIDS are B cell non-Hodgkin lymphoma and Kaposi sarcoma. A rare tumor associated with AIDS in children is leiomyosarcoma. Cervical dysplasias and carcinomas are increased in women with HIV infection, but such lesions are less frequent than lymphoma. Lung cancers at this woman's age are uncommon in any circumstance. Opportunistic infections of the brain and central nervous system lymphomas are common in patients with AIDS, but glial neoplasms are not. BP7 156-157 BP8 165 PBD7 256-258 PBD8 236-237

A 32-year-old woman with a 10-year history of intravenous drug use has developed a chronic watery diarrhea that has persisted for the past week. On physical examination, she is afebrile and has mild muscle wasting. Her body mass index is 18. Laboratory studies of the stool show cysts of Cryptosporidium parvum. One month later, she develops cryptococcal meningitis, which is treated successfully. Oral candidiasis is diagnosed 1 month later. This patient is at greatest risk of developing which of the following neoplasms?
(A) Intestinal non-Hodgkin lymphoma
(B) Adenocarcinoma of the lung
(C) Leiomyosarcoma of retroperitoneum
(D) Cervical squamous carcinoma
(E) Cerebral astrocytoma

(C) Three types of cells can carry HIV: dendritic cells, monocyte-macrophages, and CD4+ T cells. Mucosal dendritic cells (i.e., Langerhans cells) can bind to the virus and transport it to CD4+ cells in the lymph nodes. Whether the virus is internalized by mucosal dendritic cells is unclear. Monocyte-macrophages and CD4+ T cells express CD4 and the coreceptors CCR5 and CXCR4; HIV can enter these cells. Follicular dendritic cells are distinct from mucosal or epithelial dendritic cells; they trap antibody-coated HIV virions by means of their Fc receptors. The other listed cells cannot be infected by HIV. BP7 151-153 BP8 158 PBD7 248-250 PBD8 242-243

An epidemiologic study is conducted to determine risk factors for HIV infection. The study documents that individuals with coexisting sexually transmitted diseases such as chancroid are more likely to become HIV-positive. It is postulated that an inflamed mucosal surface is an ideal location for the transmission of HIV during sexual intercourse. Which of the following cells in these mucosal surfaces is most instrumental in transmitting HIV to CD4+ T lymphocytes?
(A) CD8+ cells
(B) Natural killer cells
(C) Dendritic cells
(D) Neutrophils
(E) Plasma cells

(C) This patient has graft-versus-host disease. The engrafted marrow contains immunocompetent cells that can proliferate and attack host tissues, usually skin, liver, and gastrointestinal epithelium. Tuberculin skin testing is a form of delayed-type hypersensitivity. Some chemotherapy agents can produce a drug reaction with more acute inflammation than was described in this case. Urticaria with type I hypersensitivity is a typical reaction to penicillin therapy. Patch testing is done to determine the type of allergens to which atopic individuals may react. BP7 125 BP8 134 PBD7 222-223 PBD8 230

A 35-year-old woman who has been in the hospital receiving treatment for leukemia has developed an extensive, scaling rash over the past week. A skin biopsy specimen shows keratinocyte apoptosis along the dermal-epidermal junction, with upper dermal lymphocytic infiltrates. She also has jaundice. This patient has most likely recently undergone which of the following procedures?
(A) Tuberculin skin testing
(B) Chemotherapy for malignant lymphoma
(C) Allogeneic bone marrow transplantation
(D) Penicillin therapy for pneumonia
(E) Patch testing for allergen detection

(B) These findings are characteristic of immune complex-mediated glomerulonephritis. The immune complexes activate complement and result in acute inflammation. Antibody-dependent cell-mediated cytotoxicity is initiated when IgG or IgE coats a target to attract cells that affect lysis; immune complexes do not form. Localized anaphylaxis is a type I hypersensitivity reaction that is mediated by IgE antibody. Granulomatous inflammation and T cell cytotoxicity are features of type IV hypersensitivity. BP7 118-119 BP8 126-127 PBD7 231-233 PBD8 217-219

A 20-year-old woman has had increasing malaise, oliguria, and peripheral edema for the past week. On physical examination, she has 2+ pitting edema to the knees and puffiness around the eyes. Laboratory studies show serum creatinine of 4.6 mg/dL and urea nitrogen of 42 mg/dL. A renal biopsy specimen shows positive immunofluorescent staining for immunoglobulin and complement C3 within the glomeruli. The electron microscopic appearance of the specimen is shown in the figure. Which of the following immunological mechanisms has most likely produced the renal damage seen in this patient?
(A) Antibody-dependent cell-mediated cytotoxicity
(B) Immune complex-mediated hypersensitivity
(C) Localized anaphylaxis
(D) Granulomatous inflammation
(E) T cell-mediated cytotoxicity

(A) The T-cell receptor (TCR) of a CD8+ cell clone that is specific for a particular peptide reacts and produces a cell-mediated immune response to eliminate the virally infected cells through cytotoxic action producing apoptosis. All nucleated cells display class I antigens (HLA A, B, and C). Antigen-presenting cells such as macrophages and dendritic cells (e.g., Langerhans cells) can display class II antigens (HLA DP, DQ, DR). Mast cells have IgE fixed to their surfaces that can react with allergens to cause degranulation and release of biogenic amines in type I hypersensitivity reactions. Neutrophils react nonspecifically to inflammatory stimuli. NK cells are programmed to destroy cells that do not display MHC class I antigens. Plasma cells are fully differentiated B cells that produce immunoglobulin. BP7 104-109 BP8 110-112 PBD7 203-204 PBD8 186

A macrophage ingests a virion and degrades it so that viral capsid peptides can be linked to class I HLA heavy chains and β2-microglobulin. This trimer is transported to the macrophage cell surface and displayed. Which of the following cell types has receptors that can interact with the displayed MHC-peptide complex?
(A) CD8+ lymphocyte
(B) Langerhans cell
(C) Macrophage
(D) Mast cell
(E) Neutrophil
(F) NK cell
(G) Plasma cell

(B) This patient has polymyositis. Muscle weakness in polymyositis tends to be symmetric, and proximal muscles are involved first. This condition differs from dermatomyositis in that there is no skin involvement, and polymyositis typically affects adults. On biopsy, the skeletal muscle shows infiltration by lymphocytes along with degeneration and regeneration of muscle fibers. The lymphocytes are cytotoxic CD8+ cells. Some patients may have myocarditis, vasculitis, or pneumonitis, but in contrast to dermatomyositis, the risk of cancer is equivocal. Bony ankylosis is a feature of progressive or recurrent joint inflammation with rheumatoid arthritis. Pericarditis is most likely to be a feature of systemic lupus erythematosus or diffuse systemic sclerosis. Raynaud phenomenon is seen in many autoimmune phenomena, but it is most often a feature of scleroderma. 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. Nongonococcal urethritis, conjunctivitis, and arthritis are seen in Reiter syndrome. Xerophthalmia (usually with accompanying xerostomia) is seen in Sjögren syndrome. BP7 143 BP8 151 PBD7 1342-1343 PBD8 225, 1273

A 29-year-old woman has had increasing weakness over the past year, and now has difficulty climbing a single flight of stairs. Her muscles are sore most of the time. She has little difficulty writing or typing, however. During the past 3 months, she has had increasing difficulty swallowing. She has experienced chest pain for the past week. On physical examination, she is afebrile. Her blood pressure is 115/75 mm Hg. Muscle strength is 4/5 in all extremities. No rashes are present. She has 2+ pitting edema to the knees. Rales are auscultated over lower lung fields. Laboratory studies show serum creatine kinase level of 458 U/L and Jo-1 antibodies. Which of the following conditions is she most likely to have?
(A) Bony ankylosis
(B) Myocarditis
(C) Pericarditis
(D) Raynaud phenomenon
(E) Sclerodactyly
(F) Urethritis
(G) Xerophthalmia

(E) This patient has psoriatic arthropathy. The arthritis in this condition may resemble rheumatoid arthritis clinically and pathologically. Similar to other spondyloarthropathies, sacroiliitis occurs in patients with psoriatic arthropathy. Hereditary angioedema is associated with a deficiency of complement C1 inhibitor. Cerebral lymphomas are rare, but they can occur in immunodeficiency states, particularly in patients with AIDS. Hemolytic anemia can accompany a wide variety of autoimmune phenomena and can be related to formation of specific RBC antibodies or coating of RBCs with antibody. Keratoconjunctivitis can be seen in Sjögren syndrome as a result of decreased tear production from lacrimal gland inflammation. Sclerodactyly is seen in scleroderma. When extensive, it is usually part of the spectrum of findings in diffuse scleroderma; when it involves only a few areas of the skin (e.g., just the hands), it is more likely a feature of limited scleroderma (CREST syndrome). BP7 140 BP8 147-148 PBD7 1256, 1310 PBD8 192, 1241

A 28-year-old woman has a 5-year history of severe psoriasis involving the skin of the face, trunk, and extremities and uveitis. She sees her physician because she has had increasing pain in her hands and left hip for the past 6 months. On physical examination, there is decreased range of motion of the left hip and the distal interphalangeal joints. Her fingers have a sausage-like appearance. Laboratory studies show that she is positive for HLA-B27, but ANA and rheumatoid factor test results are negative. Which of the following complications is most characteristic of this patient's illness?
(A) Angioedema of skin
(B) Cerebral lymphoma
(C) Hemolytic anemia
(D) Keratoconjunctivitis
(E) Sacroiliitis
(F) Sclerodactyly

(D) This patient has systemic lupus erythematosus (SLE). Many patients with SLE have glomerulonephritis and eventually develop renal failure. Blindness is uncommon in SLE. Raynaud phenomenon is associated with many autoimmune diseases, but it is most troublesome in scleroderma. Although synovial inflammation is common in SLE, joint deformity is rare. Libman-Sacks endocarditis associated with SLE tends to be nondeforming and limited, and there is minimal valve damage. It is now uncommon because of the use of corticosteroid therapy in the treatment of SLE. BP7 134-135 BP8 139-144 PBD7 227-231 PBD8 217-219

A 26-year-old woman has had bouts of joint pain for the past 2 years. She also has a rash on the cheeks and bridge of the nose. On physical examination, there is no joint swelling or deformity, although generalized lymphadenopathy is present. Laboratory studies indicate anemia, leukopenia, a polyclonal gammopathy, and proteinuria. The serum ANA test result is positive at a titer of 1 : 1024 with a rim pattern identified by immunofluorescence. The light microscopic and immunofluorescent (with antibody to IgG) appearances of a skin biopsy specimen are shown in the figure. Which of the following is the best information to give this patient about her disease?
(A) Blindness is likely to occur within 5 years
(B) Avoid exposure to cold environments
(C) Joint deformities will eventually occur
(D) Chronic renal failure is likely to occur
(E) Cardiac valve replacement will eventually be required

(B) Blood monocytes express MHC class II antigens and can migrate into tissues to become macrophages. In tuberculosis, these macrophages transform into epithelioid cells, forming a granuloma. Macrophages play an important role in delayed hypersensitivity reactions associated with cell-mediated immunity. Neutrophils are important mainly in acute inflammatory responses, although some neutrophils may be present in a granulomatous reaction. B cells form plasma cells that secrete immunoglobulin on stimulation and are essential to humoral immunity. Natural killer cells can function without prior sensitization. Basophils may play a role in IgE-mediated responses. BP7 107, 121 BP8 116-117 PBD7 204, 216-217 PBD8 208

In a study that examines granuloma formation in the lung in response to infection with Mycobacterium tuberculosis, it is observed that cells within the granuloma express MHC class II antigens. These cells elaborate cytokines that promote fibroblastic production of collagen within the granuloma. These class II antigen-bearing cells are most likely derived from which of the following peripheral blood leukocytes?
(A) Neutrophil
(B) Monocyte
(C) B cell
(D) Natural killer cell
(E) Basophil

(F) The reverse transcriptase gene of HIV undergoes mutation on average once per 2000 replications, a very high rate, which can account for the appearance of drug resistance. The absence of CD40 ligand interaction with CD40 explains the hyper-IgM syndrome. Chemokine receptors are important in facilitating initial HIV entry into cells, and mutations in these receptors may help explain variable susceptibility to and progression of HIV infection. The cytokine receptor γ chain is abnormal in severe combined immunodeficiency. The p24 antigen is a component of the HIV virion and is used to detect infection, but it is not a target of drug therapy. Protein tyrosine kinases are involved in signal transduction. They can be abnormal in conditions such as Bruton agammaglobulinemia, but not in patients receiving HIV drug therapy; ritonavir is an HIV protease inhibitor. BP7 149-150 BP8 157-158 PBD7 246-247 PBD8 238-239

A 38-year-old man has been infected with HIV for the past 8 years. He has been receiving highly active antiretroviral therapy for the past 18 months with a regimen that includes zidovudine, stavudine, and ritonavir. His HIV-1 RNA level initially decreased to less than 50 copies/µL after initiation of therapy; the current level is 5120 copies/µL. A mutation in the gene for which of the following substances is most likely to have occurred?
(A) CD40 ligand
(B) Chemokine receptor
(C) Cytokine receptor γ chain
(D) p24 antigen
(E) Protein tyrosine kinase
(F) Reverse transcriptase

(D) This patient is experiencing a major transfusion reaction resulting from a type II hypersensitivity reaction. The patient's serum contains naturally occurring antibodies to the incompatible donor RBCs. They attach to the donor RBCs and induce complement activation that results in generation of the C5-9 membrane attack complex. Major transfusion reactions are rare, and most result from clerical errors. Tumor necrosis factor α is not part of hypersensitivity reactions. Natural killer cell lysis is seen with antibody-mediated diseases. Antigen-antibody complex formation is typical of a type III hypersensitivity reaction. Mast cells degranulate with antigen attachment to IgE in type I hypersensitivity reactions. BP7 115 BP8 124-125 PBD7 210 PBD8 202

Laboratory tests are ordered for two hospitalized patients. During the phlebotomy procedure, the Vacutainer tubes drawn from these patients are mislabeled. One of the patients receives a blood transfusion later that day. Within 1 hour after the transfusion of RBCs begins, the patient becomes tachycardic and hypotensive and passes pink-colored urine. Which of the following statements best describes how this reaction is mediated?
(A) Release of tumor necrosis factor α into the circulation
(B) Antibody-dependent cellular cytotoxicity by natural killer cells
(C) Antigen-antibody complex deposition in glomeruli
(D) Complement-mediated lysis of RBCs
(E) Mast cell degranulation

(C) Pneumocystis jiroveci pneumonia is a common finding in patients with AIDS. This patient's low CD4+ count is characteristic of AIDS. Antineutrophil cytoplasmic autoantibody (C-ANCA or P-ANCA) can be seen in patients with vasculitis. Rheumatoid factor is present in most patients with rheumatoid arthritis; however, significant immunosuppression is not seen, unless the patients are treated with highly potent immunosuppressive drugs such as cyclosporine. The antistreptolysin O titer is elevated in patients with rheumatic fever, but there is no serious immunosuppression. The ANA test result is positive in various autoimmune diseases, but a decrease in CD4+ count is not typical of such conditions. BP7 156 BP8 162-164 PBD7 255 PBD8 245-246

A 45-year-old man has had a fever, cough, and worsening dyspnea for the past few days. On physical examination, his temperature is 39.2°C. Auscultation of the chest shows decreased breath sounds over all lung fields. A bronchoalveolar lavage is performed, and the fluid obtained yields cysts of Pneumocystis carinii. Laboratory studies show a CD4+ lymphocyte count of 135/µL; total serum globulin concentration of 2.5 g/dL; and WBC count of 7800/mm3 with 75% segmented neutrophils, 8% bands, 6% lymphocytes, 10% monocytes, and 1% eosinophils. Which of the following serologic laboratory findings is most likely to be positive in this patient?
(A) Antineutrophil cytoplasmic autoantibody
(B) Rheumatoid factor
(C) Antibodies to HIV
(D) Antistreptolysin O
(E) Anti-double-stranded DNA antibody

(B) This child had severe combined immunodeficiency (SCID), which is now treated with allogeneic bone marrow transplantation. The transplanted stem cells in the bone marrow give rise to normal T and B cells. Half of SCID cases are caused by an X-linked mutation in the common γ chain for cytokine receptors, and the rest are due to autosomal recessive mutations in the gene encoding for adenosine deaminase, which leads to accumulation of metabolites toxic to lymphocytes. An abnormal CD40 ligand interaction with CD40 leads to lack of isotype switching in patients with hyper-IgM syndrome. The BTK gene product is required for differentiation of pro-B and pre-B cells, and a mutation leads to agammaglobulinemia. Individuals lacking C2 have some increase in infections, but mainly develop a disease resembling systemic lupus erythematosus. The 22q11 deletion is seen in infants with DiGeorge anomaly and results in lack of T cell development. HIV infection leads to many opportunistic infections, which sometimes occur in infancy and early childhood, but it is mainly CD4+ lymphocytes that are diminished. BP7 146-147 BP8 153-154 PBD7 243-244 PBD8 234-235

A 14-month-old child has had multiple infections since birth, including pneumonia with Pseudomonas aeruginosa, adenovirus, and Aspergillus fumigatus; diarrhea with Isospora belli; otitis media with Haemophilus influenzae; and urinary tract infection with Candida albicans. Laboratory studies show hemoglobin, 13.2 g/dL; hematocrit, 39.7%; platelet count, 239,100/mm3; and WBC count, 3450/mm3 with 85% segmented neutrophils, 6% bands, 2% lymphocytes, and 7% monocytes. Serum immunoglobulin levels are IgG, 118 mg/dL; IgM, 14 mg/dL; and IgA, 23 mg/dL. The child dies of pneumonia. At autopsy, a hypoplastic thymus, small lymph nodes that lack germinal centers, and scant gut-associated lymphoid tissue are seen. Which of the following is the most likely cause of this disease?
(A) Abnormal CD40 ligand
(B) Adenosine deaminase deficiency
(C) BTK gene mutation C2
(D) Complement component deficiency
(E) Chromosome 22q11 deletion
(F) HIV infection

(B) About 70% to 90% of juvenile rheumatoid (idiopathic) arthritis cases resolve without joint deformity. In contrast to rheumatoid arthritis, juvenile idiopathic arthritis tends to involve lower and larger joints, and rheumatoid factor is often absent. Systemic sclerosis is a disease of adults that may have features resembling early rheumatoid arthritis, but joint destruction is rare. Psoriatic arthropathy is a disease of adults with features similar to rheumatoid arthritis, but joint involvement is more irregular. Ankylosing spondylitis occurs in older adults and principally affects the vertebral column. Reiter syndrome occurs in young to middle-aged adults; its major features are urethritis, arthritis, and conjunctivitis. BP7 139 BP8 147 PBD7 1309 PBD8 221, 1240

A 9-year-old girl has experienced pain and swelling of the elbows and knees and a fever for 1 month. On physical examination, her temperature is 38°C. There is decreased range of motion at the elbows and knees, with joint swelling and warmth. Laboratory studies show hemoglobin, 13.4 g/dL; hematocrit, 40.3%; platelet count, 288,200/mm3; and WBC count, 12,560/mm3. The ANA test result is positive, but results for rheumatoid factor, Scl-70, and SS-A serologies are negative. The girl's symptoms abate after 4 years and never recur. Which of the following is the most likely diagnosis?
(A) Systemic sclerosis
(B) Juvenile rheumatoid arthritis
(C) Psoriatic arthropathy
(D) Ankylosing spondylitis
(E) Reiter syndrome

(E) This patient is susceptible to bacterial, fungal, and viral infections and most likely has severe combined immunodeficiency (SCID). The autosomal recessive pattern of inheritance implicates adenosine deaminase (ADA) deficiency rather than mutations in the γ chain of cytokine receptors. Low ADA levels in the leukocytes are diagnostic. The other listed options are relevant to the work-up of primary immunodeficiencies, but they are not specific to SCID. BP7 146-147 BP8 153-154 PBD7 243-244 PBD8 234-235

A 9-month-old child has a history of recurrent infections with multiple agents, including cytomegalovirus, Candida albicans, Staphylococcus aureus, and Staphylococcus epidermidis. A careful family history and pedigree analysis show this to be a genetic disorder that is inherited in an autosomal recessive pattern. Which of the following laboratory studies is likely to be most useful in establishing the underlying mechanism of immunodeficiency in this infant?
(A) Quantitative serum immunoglobulin levels
(B) Enumeration of B cells in blood
(C) Enumeration of CD3+ cells in blood
(D) Tests of neutrophil function
(E) Adenosine deaminase levels in leukocytes

(D) Streptococcal M proteins cross-react with cardiac glycoproteins, resulting in rheumatic heart disease, a form of autoimmunity. Breakdown of T-cell anergy usually occurs when localized tissue damage and inflammation cause up-regulation of costimulatory molecules on the target tissues. This is a possible mechanism of autoimmunity in the brain and in pancreatic β cells. Polyclonal lymphocyte activation may be caused by microbial products such as endotoxin or bacterial superantigens. Release of sequestered antigens can cause autoimmunity; this mechanism is likely in autoimmune uveitis. Failure of T cell-mediated suppression has not yet been shown to cause any autoimmune disease; it remains a potential mechanism. The other listed options are not major immune responses to streptococcal infection. BP7 128-129 BP8 119, 124 PBD7 226-227 PBD8 212

A 12-year-old girl has complained of a sore throat for the past 3 days. On physical examination, she has a temperature of 38.4°C and pharyngeal erythema with minimal exudate. A throat culture grows group A β-hemolytic streptococcus. The pharyngitis resolves, but 3 weeks later, the girl develops fever and chest pain. Her antistreptolysin O titer is 1 : 512. Which of the following immunological mechanisms has most likely produced the chest pain?
(A) Breakdown of T-cell anergy
(B) Polyclonal lymphocyte activation
(C) Release of sequestered antigens
(D) Molecular mimicry
(E) Failure of T cell-mediated suppression

(C) Virus-infected cells are recognized and killed by cytotoxic CD8+ T cells. The T-cell receptor on the CD8+ T cells binds to the complex of viral peptide and MHC class I molecules on the surface of the infected cell. Natural killer (NK) cells also recognize MHC class I molecules with self-peptides. This recognition inhibits NK cell killing. The other listed options are not the major immune response to hepatitis infection. BP7 105, 109 BP8 109-110 PBD7 203-204 PBD8 207

Over the past week, a 32-year-old man has experienced nausea and vomiting and has become mildly icteric. On physical examination, his temperature is 37.4°C. Laboratory studies show serum AST of 208 U/L and ALT of 274 U/L. Serologic findings for HBsAg and HBcAb are positive. A liver biopsy specimen examined microscopically shows focal death of hepatocytes with a portal infiltrate composed mainly of lymphocytes. Which of the following is the most likely mechanism by which the liver cell injury occurs under these conditions?
(A) Recognition of HBsAg by the CD8 molecule of T cells
(B) Recognition of an antigenic peptide presented by MHC class I molecules to natural killer cells
(C) Recognition of an antigenic peptide presented by MHC class I molecule to CD8+ cells
(D) Destruction of HBsAg-expressing cells by anti-HBs IgG antibody
(E) Apoptosis of the liver cells by cytokines released by activated macrophages

(D) Mixed connective tissue disease can have features of systemic lupus erythematosus (SLE), polymyositis, rheumatoid arthritis, and Sjögren syndrome. In contrast to SLE or diffuse scleroderma, serious renal disease is unlikely. Dermatomyositis causes muscle pain, and the rash is typically a subtle heliotrope rash with a violaceous appearance to the eyelids; Jo-1 antibody is a more typical finding. Discoid lupus erythematosus (DLE) is characterized by a rash similar to SLE, but with immune complex deposition only in sun-exposed areas of the skin, a positive ANA test result in a few cases, absence of anti-Sm or anti-double-stranded DNA antibodies, and absence of serious renal disease. Some cases of DLE can progress to SLE. In limited scleroderma (CREST syndrome), anticentromeric antibody is often present. In Reiter syndrome (with conjunctivitis, arthritis, and nongonococcal urethritis), there is often a positive serology for HLA-B27. In Sjögren syndrome, antibodies to SS-A and SS-B are often present. The anti-Sm or anti-double-stranded DNA antibodies are more specific for SLE. BP7 143 BP8 151 PBD7 239 PBD8 226

A 41-year-old man has been bothered by a feeling of dryness in his mouth for the past 3 years. During this time, erythematous rashes have appeared on the skin of his face and upper neck. In the past 6 months, he has developed arthralgias. On physical examination, he is afebrile. There are no joint deformities. Laboratory findings include a positive ANA test result, with a speckled pattern, and high titers of antibodies to U1-ribonucleoprotein. The serum creatinine is 1.1 mg/dL, and the urea nitrogen is 17 mg/dL. Which of the following diseases is most likely to produce these findings?
(A) Dermatomyositis
(B) Discoid lupus erythematosus
(C) Limited scleroderma
(D) Mixed connective tissue disease
(E) Reiter syndrome
(F) Sjögren syndrome
(G) Systemic lupus erythematosus

(F) This patient has Goodpasture syndrome, in which an antibody is directed against type IV collagen in basement membranes of the glomeruli and in the lung. This is a form of type II hypersensitivity reaction. The antibodies attach to the basement membrane and fix complement, damaging the glomeruli. Anti-double-stranded DNA antibodies have specificity for systemic lupus erythematosus (SLE), whereas antihistone antibodies are characteristic of drug-induced SLE. Anti-Jo-1 antibody is found in dermatomyositis and polymyositis. The anti-U1-ribonucleoprotein antibody is seen in mixed connective tissue diseases. Anti-SS-A antibody is seen in Sjögren syndrome. Antiphospholipid antibodies are sometimes called "lupus anticoagulant" because they may appear in SLE; such patients have coagulopathies with thrombosis or bleeding, or both. BP7 473-474 BP8 120, 124 PBD7 210, 212 PBD8 203

A 28-year-old man has had hemoptysis and hematuria for the past 2 days. On physical examination, his temperature is 36.8°C, pulse is 87/min, respirations are 19/min, and blood pressure is 150/90 mm Hg. Laboratory studies show creatinine of 3.8 mg/dL and urea nitrogen of 35 mg/dL. Urinalysis shows 4+ hematuria, 2+ proteinuria, and no glucose. A renal biopsy specimen examined microscopically shows glomerular damage and linear immunofluorescence with labeled anticomplement and anti-IgG antibody. Which of the following autoantibodies has the greatest specificity for this patient's condition?
(A) Anti-double-stranded DNA
(B) Antihistone
(C) Anti-Jo-1
(D) Anti-U1-ribonucleoprotein
(E) Anti-SS-A
(F) Anti-basement membrane
(G) Antiphospholipid

(A) As HIV infection progresses, there is continuing, gradual loss of CD4+ cells. The stage of clinical AIDS is reached when the peripheral CD4+ count decreases to less than 200/µL, which usually occurs over 8 to 10 years. At this point, the risk of development of opportunistic infections and neoplasms typical of AIDS increases greatly. The extent of viremia also is an indication of the progression of HIV infection; an increase in HIV-1 RNA levels is seen as immunological containment of HIV fails. In HIV infection, the numbers of CD8+ lymphocytes tend to be maintained. Cells of the granulocytic series, including eosinophils, are relatively unaffected, although patients with AIDS may have cytopenias. Follicular dendritic cells can be infected by HIV and pass the virions to CD4+ cells and macrophages, but the follicular dendritic cells and the macrophages are not destroyed by the virus and become a reservoir for infection. The natural killer cells and plasma cells are not directly affected by HIV. BP7 155-156 BP8 159-162 PBD7 253-254 PBD8 244-245

A 40-year-old man has been infected with HIV for the past 10 years. During this time, he has had several bouts of oral candidiasis, but no major illnesses. He is now diagnosed with Kaposi sarcoma involving the skin. He has had a 7-kg weight loss in the past 6 months. Laboratory studies show the HIV-1 RNA viral load is currently 60,000 copies/mL. Which of the following types of cells is most depleted in his lymph nodes?
(A) CD4+ lymphocyte
(B) CD8+ lymphocyte
(C) Eosinophil
(D) Follicular dendritic cell
(E) Macrophage
(F) Natural killer cell
(G) Plasma cell

(B) This patient has cutaneous and visceral manifestations of diffuse systemic sclerosis (diffuse scleroderma). Raynaud phenomenon, skin changes, and esophageal dysmotility also can occur in limited scleroderma (CREST syndrome), but lung and renal involvement typically do not. In diffuse systemic sclerosis, the anti-DNA topoisomerase I antibody is often present, and patients can develop interstitial lung disease and renal disease with hyperplastic arteriolosclerosis. A feature of discoid lupus erythematosus is skin rashes, but usually there is no internal organ involvement. Ankylosing spondylitis is one of the spondyloarthropathies; it is characterized by low back pain from sacroiliitis and positive serology for HLA-B27. Reiter syndrome is characterized by conjunctivitis, arthritis, and nongonococcal urethritis, with a positive serology for HLA-B27. In rheumatoid arthritis, there is often progressive joint deformity; the serologic tests likely to be positive include rheumatoid factor and antibodies to cyclic citrullinated peptide (anti-CCP). The anti-Sm or anti-double-stranded DNA antibodies are more specific for systemic lupus erythematosus, and renal disease in these patients is most likely due to glomerulonephritis. BP7 141-143 BP8 148-151 PBD7 237-239 PBD8 223-225

For the past 2 years, a 42-year-old woman has had tightening of the skin of her fingers, making them difficult to bend. She has had increasing difficulty swallowing for the past 8 months. During the past winter, her fingers became cyanotic and painful on exposure to cold. On physical examination, the skin on her face, neck, hands, and forearms appears firm and shiny. Her blood pressure is 150/95 mm Hg. A chest radiograph shows prominent interstitial markings, and lung function tests indicate moderately severe restrictive pulmonary disease. The result of the DNA topoisomerase I antibody test is positive. Which of the following conditions is most likely to produce these findings?
(A) Ankylosing spondylitis
(B) Diffuse systemic sclerosis
(C) Discoid lupus erythematosus
(D) Limited scleroderma
(E) Reiter syndrome
(F) Rheumatoid arthritis
(G) Systemic lupus erythematosus

(B) Amyloidosis is most often caused by excessive light-chain production with plasma cell dyscrasias such as multiple myeloma (AL amyloid). Chronic inflammatory conditions, such as rheumatic fever, ankylosing spondylitis, and systemic sclerosis, also may result in amyloidosis (AA amyloid), but not in secretion of light chains in urine (i.e., Bence Jones proteinuria). Immunoglobulin levels generally are reduced in patients with common variable immunodeficiency. BP7 159-160 BP8 166-168 PBD7 260-261 PBD8 250-252

A 61-year-old man has had increasing malaise for the past 4 months. On physical examination, he is afebrile and has mild muscle wasting. Laboratory studies show serum creatinine of 4.5 mg/dL and urea nitrogen of 44 mg/dL. Urine dipstick analysis shows no blood, protein, or glucose, but a specific test for Bence Jones proteins yields a positive result. A renal biopsy specimen has the microscopic appearance shown in the figure. Which of the following underlying conditions is most likely to be present in this patient?
(A) Rheumatic fever
(B) Multiple myeloma
(C) Ankylosing spondylitis
(D) Systemic sclerosis
(E) Common variable immunodeficiency

(D) Perivascular accumulation of T cells, particularly CD4+ cells, is typical of delayed hypersensitivity skin reactions, driven by a TH1 response mediated largely by release of the cytokine interleukin-2. Systemic anaphylaxis typically occurs within minutes after an encounter with the antigen. Systemic and localized immune complex diseases (serum sickness and Arthus reactions) are type III hypersensitivity reactions; they often exhibit vasculitis. Graft-versus-host disease is characterized by epidermal apoptosis and rash. BP7 119-120 BP8 128-130 PBD7 216-217 PBD8 205-207

A 40-year-old laboratory technician accidentally injects a chemical into his skin. The next day, he notes that an area of erythematous, indurated skin is forming around the site of injection. Two days later, the induration measures 10 mm in diameter. A microscopic section from this area, with immunostaining using antibody to CD4, shows many positive lymphocytes. Which of the following immunological reactions is most consistent with this appearance?
(A) Systemic anaphylaxis
(B) Arthus reaction
(C) Graft-versus-host disease
(D) Delayed-type hypersensitivity
(E) Serum sickness

(A) Acute rejection of kidney transplants occurs weeks, months, or years after transplantation. It is characterized by infiltration with CD3+ T cells that include the CD4+ and CD8+ subsets. These cells damage tubular epithelium by direct cytotoxicity and by release of cytokines, such as interferon-γ, which activate macrophages. The reaction is called acute cellular rejection, and it can be readily treated with corticosteroids. Interstitial and glomerular fibrosis and blood vessel thickening occur in chronic rejection. Fibrinoid necrosis and thrombosis are more typical of hyperacute rejection, which occurs within minutes of placement of the transplant into the recipient. Eosinophils accumulate in acute interstitial nephritis owing to drug reactions. Amyloid derived from serum amyloid-associated protein can occur in chronic infections and inflammation. BP7 122-123 BP8 131-134 PBD7 218-220 PBD8 228-229

A 19-year-old woman with chronic renal failure received a cadaver renal transplantation. One month later, she experienced increasing serum creatinine and urea nitrogen levels, and a renal biopsy was performed. She was treated with corticosteroids, and her renal function improved. Which of the following changes was most likely seen in the biopsy specimen before corticosteroid therapy was initiated?
(A) Interstitial infiltration by CD3+ lymphocytes and tubular epithelial damage
(B) Extensive fibrosis of the interstitium and glomeruli with markedly thickened blood vessels
(C) Fibrinoid necrosis of renal arterioles with thrombotic occlusion
(D) Interstitial infiltration by eosinophils with tubular epithelial damage
(E) Glomerular deposition of serum amyloid-associated protein

(E) This patient has rheumatoid arthritis. The pannus of rheumatoid arthritis leads to joint destruction and ankylosis with marked deformity. There are few other organ-specific lesions, although rheumatoid nodules can be found under the skin over bony prominences and in organs such as the lung and heart. Renal failure is more likely in systemic lupus erythematosus. Aortic dissection is more likely in Reiter syndrome. Ankylosing spondylitis is marked by kyphosis. The risk of malignancies is increased in patients with autoimmune diseases, although malignancies are still uncommon. BP7 136-138 BP8 145-147 PBD7 1305-1309 PBD8 221, 1237-1240

A 35-year-old woman has had bouts of severe pain and swelling of the small joints of her hands and feet for the past 10 years, although she has had remissions during each of her three pregnancies. She has been bedridden for the past 2 months. On physical examination, there is warmth, swelling, and tenderness of the hands and feet, deformity of the hands, and ulnar deviation and decreased range of motion of metacarpophalangeal and interphalangeal joints. She has no muscle pain or skin rash. A painless 1.5-cm subcutaneous nodule is present behind the elbow joint over the olecranon process. A joint aspirate shows turbid fluid with many neutrophils containing phagocytized immune complexes. Which of the following long-term outcomes of this patient's disease is most likely to occur?
(A) Chronic renal failure
(B) Aortic dissection
(C) Vertebral kyphosis
(D) Adenocarcinoma of the colon
(E) Joint deformities

(C) This patient has Sjögren syndrome, which primarily involves salivary and lacrimal glands. Antibodies to SS-B are found in 60% to 90% of patients. Anti-double-stranded DNA is a specific autoantibody for systemic lupus erythematosus. Anticentromere antibody is seen in systemic sclerosis. Scl-70 is a marker for diffuse systemic sclerosis. Jo-1 is a marker for polymyositis. BP7 139-140 BP8 148 PBD7 235-237 PBD8 221-223

A 45-year-old woman has had a burning sensation with increasing blurring of vision for the past 5 years. On physical examination, she has keratoconjunctivitis. Atrophy of the oral mucosa, with buccal mucosal ulcerations, also is present. A biopsy specimen of the lip shows marked lymphocytic and plasma cell infiltrates in minor salivary glands. Which of the following antibodies is most likely to be identified on laboratory testing?
(A) Anti-double-stranded DNA
(B) Anticentromere
(C) SS-B
(D) Scl-70
(E) Jo-1

(E) This patient is experiencing a systemic anaphylactic reaction, a form of type I hypersensitivity. IgE is bound to mast cells, after previous sensitization, so that a repeat encounter with the antigen results in mast cell degranulation and the release of mediators, such as histamine, which lead to anaphylaxis. IgE also is important in mediating more localized inflammatory reactions such as allergic rhinitis (hay fever). Other immunoglobulins do not bind so readily to mast cells. BP7 112-114 BP8 120-124 PBD7 209 PBD8 201

A 22-year-old man has had a urethral discharge for the past week. A culture of the exudate from the urethra grows Neisseria gonorrhoeae. He is treated with penicillin G, but within minutes after injection, he develops itching and erythema of the skin. This is quickly followed by severe respiratory difficulty with wheezing and stridor. Which of the following immunoglobulins has most likely become attached to the penicillin G and mast cells to produce these symptoms?
(A) IgA
(B) IgG
(C) IgM
(D) IgD
(E) IgE

(D) These findings point to the X-linked disorder known as Wiskott-Aldrich syndrome, which is characterized by thrombocytopenia, eczema, and decreased IgM. IgA may be increased. As in many immunodeficiency disorders, there is an increased risk of non-Hodgkin lymphoma. Hypocalcemia is seen in neonates with DiGeorge syndrome. Rheumatoid arthritis can complicate isolated IgA deficiency and common variable immunodeficiency, conditions with survival to adulthood. A deficiency of complement component C3 may be complicated by immune complex glomerulonephritis. Dementia can be seen in patients with AIDS. BP7 147 BP8 155 PBD7 244 PBD8 235

A 4-year-old boy has had recurrent respiratory infections with multiple bacterial and viral pathogens for the past 3 years. On physical examination, he has eczema involving the trunk and extremities. Laboratory findings include a platelet count of 71,000/mm3 and WBC count of 3800/mm3 with 88% segmented neutrophils, 6% bands, 3% lymphocytes, and 3% monocytes. Serum immunoglobulin levels are IgG, 1422 mg/dL; IgM, 11 mg/dL; and IgA, 672 mg/dL. This patient is at an increased risk of developing which of the following conditions?
(A) Hypocalcemia
(B) Rheumatoid arthritis
(C) Glomerulonephritis
(D) Malignant lymphoma
(E) Dementia

(A) Individuals infected with HIV are infected for life. They can transmit the virus to others via sexual intercourse even if they appear to be well. The average time for the development of AIDS after HIV infection is 8 to 10 years. Seroreversion in HIV infection does not occur. Screening questionnaires and serologic testing can prevent this individual from being a blood donor. HIV infection affects mainly CD4+ lymphocytes, with declining CD4+ counts presaging the development of clinically apparent AIDS. Antibody titers do not predict clinical illness or complications. Progression of HIV disease is monitored by levels of HIV-1 mRNA in the blood and by CD4+ cell counts. BP7 155-156 BP8 162-163 PBD7 245-246 PBD8 244

A 17-year-old boy has been sexually active for the past 3 years. Serologic testing shows that he is HIV-positive. He is currently healthy and is not an intravenous drug user. Which of the following is the best information to give this patient about his disease?
(A) You should not have unprotected sex with other individuals
(B) You will probably develop AIDS within 1 year
(C) Your HIV test may become negative within 1 year
(D) As long as you are clinically well, you can donate blood
(E) The course of your infection is best followed by titers of anti-HIV antibodies

(C) These findings are characteristic of cardiac amyloidosis. Because of the patient's age, a senile cardiac amyloidosis, resulting from deposition of transthyretin, is most likely. α-Fetoprotein is present during fetal life, but it is best known in adults as a serum tumor marker. β2-Microglobulin contributes to the development of amyloidosis associated with long-term hemodialysis. Calcitonin forms the precursor for amyloid deposited in thyroid medullary carcinomas. Amyloidosis associated with plasma cell dyscrasias results from light-chain production. Although the heart is commonly involved in light-chain amyloidosis, the normal laboratory values and absence of plasma cell collections in the marrow argue against a plasma cell dyscrasia. IgE is not a component of amyloid. BP7 160-161 BP8 168-170 PBD7 263 PBD8 253-254

A 79-year-old man has experienced worsening congestive heart failure and pulmonary and peripheral edema for the past 4 years. On physical examination, his temperature is 36.9°C, pulse is 70/min, respirations are 16/min, and blood pressure is 120/75 mm Hg. Echocardiography shows cardiomegaly with four-chamber dilation. All laboratory studies, including serum protein electrophoresis and examination of bone marrow smear, are normal. An endomyocardial biopsy specimen has the histologic appearance shown in the figure. Which of the following proteins is most likely to be found in this lesion?
(A) α-Fetoprotein
(B) β2-Microglobulin
(C) Transthyretin
(D) Calcitonin
(E) IgE

(D) This boy most likely has Bruton agammaglobulinemia, an X-linked primary immunodeficiency marked by recurrent bacterial infections that begin after maternal antibody levels diminish. Selective IgA deficiency is marked by a more benign course, with sinopulmonary infections and diarrhea that are not severe. Deficiency of complement C3 is rare; it leads to greater numbers of infections in children and young adults, but Giardia infections are not a feature of this disease. Lack of cell-mediated immunity is more likely to be seen in HIV infection in children. Although some patients with Bruton agammaglobulinemia can develop features of systemic lupus erythematosus, they generally do not have a positive test result for ANA. BP7 144-145 BP8 152-153 PBD7 240-242 PBD8 231-232

A 2-year-old boy has had almost continuous infections since he was 6 months old. These infections have included otitis media, pneumonia, and impetigo. Organisms cultured have included Haemophilus influenzae, Streptococcus pneumoniae, and Staphylococcus aureus. He also has had diarrhea, with Giardia lamblia cysts identified in stool specimens. The family history indicates that an older brother with a similar condition died because of overwhelming infections. The boy's two sisters and both parents are normal. Which of the following laboratory findings would most likely be seen in this boy?
(A) Absence of IgA
(B) Decreased complement C3
(C) High titer of HIV-1 RNA
(D) Agammaglobulinemia
(E) Positive ANA test result

(B) This woman has hereditary angioedema, a rare autosomal-recessive disorder in which there is a deficiency of antigenic or functional C1 inhibitor, resulting in recurrent episodes of edema. Of the remaining choices, only C3 and IgA have a deficiency state. C3 deficiency is accompanied by recurrent infections with pyogenic bacteria. IgA deficiency leads to mild recurrent gastrointestinal and respiratory tract infections and predisposes to anaphylactic transfusion reaction. β2-Microglobulin is a component of MHC class I; it can be increased with HIV infection and can be a substrate for amyloid fibrils in patients receiving long-term hemodialysis. 5-Hydroxytryptamine (serotonin) has an effect similar to histamine, which drives vasodilation and edema. IgE participates in localized or systemic anaphylaxis with edema. BP7 147 BP8 155 PBD7 244-245 PBD8 235

A 39-year-old woman sees her physician because of acute onset of severe dyspnea. On physical examination, she is afebrile and has marked laryngeal stridor and severe airway obstruction. The medical history indicates that she has had similar episodes since childhood and episodes of colicky gastrointestinal pain. Her mother and her brother are similarly affected. There is no history of severe or recurrent infections. She does not have urticaria. Laboratory studies show normal WBC count, hematocrit, and platelet count. A deficiency in which of the following plasma components is most likely to produce these findings?
(A) β2-Microglobulin
(B) C1 inhibitor
(C) C3
(D) 5-Hydroxytryptamine
(E) IgA
(F) IgE

(F) Natural killer (NK) cells have CD16, an Fc receptor that allows them to bind to opsonized cells and lyse them. This is a form of type II hypersensitivity with antibody-mediated disease. NK cells comprise 10% to 15% of circulating lymphocytes. NK cells also may lyse human cells that have lost MHC class I expression as a result of viral infection or neoplastic transformation. B cells have surface immunoglobulin, are CD19 positive, and participate in humoral immunity. CD4+ cells are T lymphocytes that are "helper" cells; they have T cell receptors and are CD3 positive. Likewise, CD8+ cells have T cell receptors and mark with CD3, but they act as cytotoxic T lymphocytes. Dendritic cells are a form of antigen-presenting cell that expresses large amounts of MHC class II molecules. Macrophages express MHC II and act as antigen-presenting cells to CD4+ cells; they can phagocytize opsonized cells. Stem cells are CD34 positive and can give rise to the whole range of cells in the immune system and blood-forming cells. BP7 107, 115 BP8 108, 113, 125 PBD7 210 PBD8 188

In an experiment, a cell line derived from a human malignant neoplasm is grown in culture. A human IgG antibody is added to the culture, and the tumor cells are observed to be coated by the antibody, but they do not undergo lysis. Next, human cells are added that are negative for CD3, CD19, surface immunoglobulin, and T-cell receptor markers, but are positive for CD16 and CD56. The tumor cells are observed to undergo lysis. Which of the following human cell types added to the tumor cell culture is most likely to produce these findings?
(A) B cell
(B) CD4+ cell
(C) CD8+ cell
(D) Dendritic cell
(E) Macrophage
(F) Natural killer cell
(G) Stem cell

(C) Dendritic cells are a form of antigen-presenting cell. Dendritic cells in epithelia are known as Langerhans cells, and those within germinal centers are called follicular dendritic cells (FDCs). The FDCs may become infected, but not killed by HIV. They have cell surface Fc receptors that capture antibody-coated HIV virions through the Fc portion of the antibody. These virions attached to the FDCs can infect passing CD4+ lymphocytes. B cells are a component of humoral immunity, and antibody to HIV does not serve a protective function, but allows serologic detection of infection. CD8+ cells are cytotoxic lymphocytes that lack the receptor necessary for infection by HIV. Because they survive selectively, the CD4+:CD8+ ratio is reversed; it is typically less than 1 with advanced HIV infection. Langhans giant cells are "committees" of activated macrophages that are part of a granulomatous response. Macrophages are a type of antigen-presenting cell that can become infected by HIV without destruction. Mast cells have surface-bound IgE, which can be cross-linked by antigens (allergens) to cause degranulation and release of vasoactive amines, such as histamine, as part of anaphylaxis with type I hypersensitivity. Natural killer cells have Fc receptors, but they are not antigen-presenting cells. BP7 107, 153 BP8 113 PBD7 199-200 PBD8 187, 243

During heterosexual intercourse, seminal fluid containing HIV contacts vaginal squamous mucosa. The virions are captured by cells, which then transport the virus via lymphatics to the regional lymph nodes. Within the germinal centers of these lymph nodes, the virions infect CD4+ lymphocytes and proliferate, causing CD4 lysis with release of more virions, which are taken up on the surface of cells having Fc receptors, allowing continued infection by HIV of more CD4+ cells passing through the nodes. Which of the following types of cells is most likely to capture HIV onto its surface via Fc receptors?
(A) B cell
(B) CD8+ cell
(C) Follicular dendritic cell
(D) Langhans giant cell
(E) Macrophage
(F) Mast cell
(G) Natural killer cell

(E) The TH17 subset of CD4 cells plays a role in delayed-type hypersensitivity reactions. Many persons react to nickel, particularly with body piercing jewelry. IL-17 may also be useful in recruiting neutrophils to fight bacterial as well as fungal infections such as aspergillosis and candidiasis. IL-2 acts as an autocrine growth factor promoting T cell proliferation. IL-5 activates eosinophils as part of a TH2 response. IL-10 is an immunosuppressive cytokine that diminishes lymphocyte activation. NK cells may secrete interferon-gamma in response to stimulation by IL-12. BP7 119-120 BP8 128-130 PBD7 215-217 PBD8 195, 206

Persons with sensitivity to body jewelry undergo skin patch testing with nickel compounds. Within 24 to 48 hours there is focal erythema and induration of their skin. A subpopulation of CD4+ T lymphocytes is secreting a cytokine that is recruiting neutrophils and monocytes to this inflammatory reaction, accompanied by itching and pain. Which of the following interleukins is this cytokine most likely to be?
(A) IL-2
(B) IL-5
(C) IL-10
(D) IL-12
(E) IL-17

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