6. Diseases of Immunity Flashcards
1 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) Defective clearance of apoptotic nuclei
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.
2 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) Recurrent thrombosis
(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.)
3 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) Chemokine receptor
(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.)
4 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)
Abnormal CD40-CD40L interaction
(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.)
5 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
(B) Epinephrine
(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.)
6 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) Hemolytic anemia
(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).)
7 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
(C) Non-Hodgkin lymphoma
(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.)
8 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
(B) Streptococcus pneumoniae
(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.)
9 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
(D) Human herpesvirus-8
(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.)
10 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
(A) CD4+ lymphocytes
(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.)
11 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
(E) Anti-Jo-1 antibodies
(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.)
12 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
(B) Anti-Sm
(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.)
13 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
(A) Antibody Fc receptor–mediated inflammation
(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.)
14 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
(B) Vascular intimal fibrosis
(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.)
15 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
(A) Natural killer cell
(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.)
16 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
(E) Selective IgA deficiency
(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.)
17 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
(C) Neutrophils, eosinophils, and CD4+ lymphocytes
(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.)
18 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
(B) Macrophage
(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.)
19 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) Decreased complement C3
(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.)
20 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
(C) It is derived from an acute-phase reactant
(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.)
21 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
(B) Antihistone
(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.)
22 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
(F) Pre-B cell
(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.)
23 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) Mutation in the common γ chain of cytokine receptors
(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.)
24 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
(C) Antibody-mediated dysfunction of neuromuscular junction
(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.)
25 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
(E) Malignant hypertension
(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.)
