WK 2: Immunopathology Flashcards
A 15-year-old healthy girl with no major medical problems notes blotchy areas of erythema that are pruritic over the skin of her arms, legs, and trunk within an hour every time she eats seafood, followed by diarrhea. These problems abate within 3 hours, and then physical examination reveals no abnormal findings. Which of the following immunologic abnormalities is she most likely to have?
A Localized anaphylaxis
B Cell-mediated hypersensitivity
C Complement activation
D Hypergammaglobulinemia
E Immune complex deposition
(A) CORRECT. Food allergies are typically a form of type I hypersensitivity reaction. The allergens react with IgE bound to mast cells mainly located in dermis of skin and submucosa of gastrointestinal tract. More severe allergic reactions may be termed systemic and life-threatening from airway obstruction and circulatory collapse.
A 55-year-old previously healthy man has developed progressive renal failure for the past 5 years along with back pain. Microscopic examination of a renal biopsy shows extensive glomerular and vascular deposition of pink amorphous material on H&E staining. This material demonstrates apple-green birefringence under polarized light after Congo red staining. Immunohistochemical staining of these deposits is positive for lambda light chains. Which of the following conditions is most likely to be present in this man?
A Rheumatoid arthritis
B Tuberculosis
C Systemic lupus erythematosus
D Multiple myeloma
E Alzheimer disease
(D) CORRECT. The light chains are elaborated by plasma cells. Light chains from a plasma cell abnormality contribute to the formation of AL amyloid, in his case affecting renal function. Not all patients with AL amyloid, however, have multiple myeloma, and conversely just a subset of myeloma patients develop amyloidosis. The back pain suggests vertebral bone involvement by multiple myeloma.
A 22-year-old woman has experienced episodes of myalgias, chest pain, and arthralgias for the past 3 years. On examination a friction rub is audible on chest auscultation and there is dullness to percussion at posterior lung bases. No joint deformities are noted. She has continued working at her job. She has a mild normocytic anemia. A chest x-ray shows bilateral pleural effusions. Which of the following laboratory screening tests is most appropriate to begin the workup for her condition?
A CD4 lymphocyte count
B Blood culture
C Antinuclear antibody test
D Sedimentation rate
E Creatine phosphokinase
(C) CORRECT. These non-specific findings put together suggest possible autoimmune disease. An ANA is a good way to begin the workup, then more specific tests can be ordered. Antigen-antibody complexes of many autoimmune diseases can precipitate in a variety of locations, typically trapped in basement membranes in sites such as skin, synovium, pleura, pericardium, and glomeruli. The complexes elicit an inflammatory reaction with exudates/transudates.
A male infant is born at term. No congenital anomalies are noted on examination. A year later he now has failure to thrive and has been getting one bacterial pneumonia after another with both Hemophilus influenzae and Streptococcus pneumoniae cultured from his sputum. Which of the following diseases is he most likely to have?
A DiGeorge syndrome
B Selective IgA deficiency
C Epstein-Barr virus (EBV) infection
D Acute leukemia
E X-linked agammaglobulinemia
(E) CORRECT. Recurrent bacterial infections suggest a lack of B-cell immune function with lack of gamma globulin production. Once protective maternal antibodies are gone, the disease is manifested more severely.
A 52-year-old man with chronic kidney disease receives a renal allograft with matching by tissue typing for HLA-DR (Class II) antigens. He does not develop rejection as a complication. His serum creatinine remains in the normal range. Which of the following immunologic abnormalities has most likely been avoided by the tissue typing?
A Amyloidosis
B Cell lysis by CD8 lymphocytes
C Graft versus host disease
D CD4 lymphocyte activation
E Serum sickness
(D) CORRECT. Class II HLA antigens are involved in the process of CD4 lymphocyte activation.
A 5-year-old boy and his 4-year-old brother have had recurrent pneumonia, meningoencephalitis, sinusitis, otitis, and diarrhea since infancy. Bacterial and viral agents have been implicated, as well as Pneumocystis, Giardia, and Cryptosporidium. Laboratory studies show serum IgG 47 mg/dL, IgA 5 mg/dL, and IgM 671 mg/dL. Normal numbers of B and T cells are present. These children are most likely to have a mutation involving a gene encoding for which of the following?
A NADPH oxidase
B Wiskott-Aldrich syndrome protein
C Cytokine receptor common gamma chain
D CD40L
E Complement C1 inhibitor
(D) CORRECT. They have hyper-IgM syndrome, an X-linked disorder. The CD40-CD40L interaction is involved with isotype switching from IgM production, thus accounting for a very high IgM but very low IgG and IgA. This accounts for bacterial infections. However, some degree of cell mediated immune defect can be present as well.
A 20-year-old woman has had symmetrical, proximal muscle weakness for 6 months. On exam she has 4/5 motor strength in all extremities. A deltoid biopsy shows scattered inflammatory infiltrates with focal necrosis of the muscle fibers. Her antinuclear antibody test is positive along with anti-Mi-2, but negative histidyl-tRNA synthetase (Jo-1) antibody in her serum. Which of the following additional findings would be most likely be present in this patient?
A Heart failure
B Malabsorption
C Peripheral neuropathy
D Skin rash
E Renal failure
(D) CORRECT. She has an immune myositis, and with skin involvement may be termed dermatomyositis, though muscle or skin involvement may be minimal or absent, and there is overlap with what could be termed polymyositis more likely to have a positive Jo-1 autoantibody. The sensitivity and specificity of autoimmune serologies can be low, and a panel of serologic tests may help resolve the diagnosis. The violaceous skin rash is often quite subtle and typically limited to the face. There is a risk for development of a carcinoma, linked to immune dysregulation with this disorder.
A hypersensitivity response of the immune system is noted to be stimulated by release of IL-4 and IL-5. This is accompanied by eosinophilia. This response is most likely be directed against which of the following?
A Amyloid protein
B Spirochetes
C Neoplasms
D Inhaled dusts
E Liver flukes
(E) CORRECT. Parasitic infestations with organisms that invade tissues can be accompanied by an eosinophilic response, aided by stimulation of TH2 immune response, with elaboration of IL-4 and IL-5. The parasite can trigger an IgE response by binding to Fc receptors on mast cells, eosinophils, and basophils, causing degranulation and cytokine release.
A 54-year-old woman has noted that during the past month her fingers become pale and painful upon exposure to cold. On exam she has mild dyspnea, but no wheezing. Her blood pressure is 170/110 mm Hg. Her antinuclear antibody test is positive with a titer of 1:256 and a nucleolar pattern. Her serum urea nitrogen is 15 mg/dL with creatinine of 1.1 mg/dL. Which of the following autoimmune diseases is she most likely to have?
A Discoid lupus erythematosus (DLE)
B Systemic sclerosis
C Immune myositis
D Sjogren’s syndrome (SS)
E Rheumatoid arthritis (RA)
(B) CORRECT. The nucleolar pattern suggests scleroderma (systemic sclerosis) more than the other autoimmune diseases, and likely diffuse scleroderma. Complications of scleroderma include hypertension, though signs of renal failure may not occur unless the complication of hypertensive emergency (malignant hypertension) when systolic pressure is ≥180 and/or diastolic pressure ≥120 mmHg along with signs of acute or ongoing end-organ damage supervenes. She also has features of Raynaud phenomenon and pulmonary fibrosis.
Twelve hours after going on a hike through dense foliage, a 40-year-old man notices a slightly raised and tender irregular reddish rash on one forearm that was not covered by clothing. This rash gradually increases in intensity for 2 days and then fades away after two weeks. Which of the following forms of immunologic hypersensitivity is most likely demonstrated in this patient?
A Type I hypersensitivity
B Type II hypersensitivity
C Type III hypersensitivity
D Type IV hypersensitivity
(D) CORRECT. This is a contact dermatitis, typical of exposure to a plant such as poison ivy.
A 30-year-old woman has experienced myalgias for the past 3 months. On physical examination she has 5/5 motor strength in all extremities. She has dullness to percussion at lung bases. A chest x-ray shows bilateral pleural effusions. Laboratory studies show a positive antinuclear antibody test at a titer of 1:1024. Her serum urea nitrogen is 30 mg/dL. A renal biopsy is performed and microscopic examination shows a granular pattern of immunofluorescence staining with antibody to complement component C1q. This pattern is most typically produced as a consequence of which of the following immunologic mechanisms?
A IgE coating mast cells
B Antiglomerular basement membrane antibody
C Antigen-antibody complexes
D Macrophage release of lymphokines
E Release of prostaglandins
(C) CORRECT. A granular pattern of glomerular immunofluorescence staining is typical of immune complex deposition that occurs with a type III hypersensitivity reaction. This patient’s findings suggest SLE.
The second pregnancy for a 23-year-old woman appears uncomplicated until ultrasound performed at 19 weeks shows hydrops fetalis. The fetal organ development is consistent for 19 weeks, and no congenital anomalies are noted. Her first pregnancy was uncomplicated and resulted in the birth of a normal girl at term. The current pregnancy ends with birth of an infant boy at 32 weeks gestation. On examination the infant has marked icterus. Laboratory studies show a hemoglobin of 7.5 g/dL, and neonatal exchange transfusion is performed. Which of the following immunologic mechanisms best explains this infant’s findings?
A Anti-receptor antibody
B Loss of self tolerance
C Immune complex formation
D Delayed type hypersensitivity
E Complement mediated cell destruction
E) CORRECT. This is immune hydrops, probably from Rh incompatibility, resulting in maternal antibody crossing the placenta and destroying baby’s RBCs through complement mediated lysis, a form of type II hypersensitivity reaction.
A previously healthy 12-year-old girl develops a sore throat over the past 2 days. On physical examination she has marked pharyngeal erythema with overlying yellowish exudate. A throat culture grows group A beta-hemolytic Streptococcus. Her pharyngitis resolves, but 3 weeks later she develops chest pain along with fever and malaise. The girl describes aching of her knees, hips, shoulders, and elbows. Multiple subcutaneous skin nodules are noted on physical examination, and she exhibits slight shaking movements of her head and neck. Her antistreptolysin-O and anti-DNAse B titers are elevated. Her creatine kinase MB fraction is elevated. Her findings are most likely the result of which of the following immunologic mechanisms?
A Bypass of low-zone tolerance through cross-reactivity
B Deposition of antigen-antibody complexes in multiple tissue
C Formation of an antibody to immune complexes
D Exposure of a previously sequestered antigen
E Interaction between genetic predisposition and environmental insults
(A) CORRECT. Acute rheumatic fever follows a group A beta hemolytic streptococcal infection. There is cross-reactivity of the immune response to streptococcal M proteins, with the heart mainly affected. The incidence of rheumatic fever is now so low that strict criteria must be applied for antibiotic treatment of pharyngitis.
A 60-year-old woman has developed crippling arthritis over the past 20 years. On physical examination the arthritis primarily involves her hands and feet, with marked joint deformities characterized by ulnar deviation and swan-neck deformities of her fingers. She has an irregular heart rate. Laboratory studies show that her rheumatoid factor and cyclic citrulinnated peptide serologic titers are markedly elevated, but her antinuclear antibody test is negative. A rectal biopsy shows submucosal deposition of pink amorphous material that stains positively with Congo red. Which of the following precursor proteins most likely gave rise to these rectal deposits?
A Serum amyloid-associated protein
B Lambda immunoglobulin light chains
C Transthyretin
D Amyloid precursor protein
E Beta-2-microglobulin
(A) CORRECT. She has rheumatoid arthritis, which is a chronic inflammatory condition that can be complicated by amyloidosis of the reactive systemic variety with SAA protein contributing to amyloid deposition in a variety of organs.
A 35-year-old man has experienced a malar skin rash, polyarthritis with swelling and warmth of his hands, and sensitization to cold for the past 6 months. On physical examination he has generalized lymphadenopathy and pale conjunctivae. Laboratory findings include a hemoglobin of 9.5 g/dL, total WBC count of 2100/microliter, total serum protein 8.8 g/dL, albumin 3.6 g/dL, creatinine 1.1 mg/dL, and creatine kinase of 468 U/L. His antinuclear antibody test is positive at 1:256. Which of the following additional serologic tests is most likely to determine his underlying disease process?
A Anti-centromere
B Anti-RNP
C Rheumatoid factor
D Serum C1q complement level
E HIV test
(B) CORRECT. The anti-RNP suggests a diagnosis of mixed connective tissue disease (MCTD), which has elements of SLE, rheumatoid arthritis, and scleroderma. Unlike SLE, MCTD is less likely to be accompanied by severe renal complications, but some cases evolve to SLE. Like scleroderma, MCTD is likely to result in severe pulmonary fibrosis.
