Immunopathology (Hypersensitivity, Autoimmunity, Immunodeficiency, Amyloidosis) MCQs

Pathology · 160 free questions with answers & explanations.

1. A 55-year-old man with longstanding rheumatoid arthritis develops nephrotic syndrome. Renal biopsy stained with Congo Red shows apple-green birefringence under polarized light in the mesangium and vessel walls. Immunohistochemistry identifies serum amyloid A (SAA) protein in the deposits. This is best classified as:
2. A 30-year-old woman develops hemolytic anemia, thrombocytopenia, and a rash following methyldopa therapy. The underlying mechanism of drug-induced autoimmune hemolytic anemia in this case involves:
3. In X-linked agammaglobulinemia (Bruton disease), the underlying defect is mutation of BTK, a tyrosine kinase essential for which developmental step?
4. A 22-year-old receives a blood transfusion and within minutes develops urticaria, bronchospasm, hypotension, and angioedema. His serum IgA levels are undetectable. The mechanism of this severe anaphylactic transfusion reaction in IgA-deficient patients is:
5. AA amyloidosis (reactive/secondary amyloidosis) develops in patients with chronic inflammatory conditions. The serum precursor protein that forms AA fibrils is:
6. Seronegative myasthenia gravis (MuSK-antibody positive) differs from classic AChR-antibody MG in which pathological mechanism?
7. X-linked severe combined immunodeficiency (X-SCID) is caused by mutation in the gene encoding the common gamma chain (γc, CD132) shared by multiple cytokine receptors. The absence of which signal transducer downstream of γc leads to impaired T-cell development?
8. In the seronegative spondyloarthropathies, HLA-B27 antigen association is strong. The molecular mimicry hypothesis proposes that HLA-B27 presentation of which type of microbial antigen triggers autoimmunity?
9. The Gell and Coombs classification of hypersensitivity reactions places contact dermatitis to nickel in which type, and what is the characteristic effector cell?
10. A 60-year-old man with IgG kappa multiple myeloma develops macroglossia, periorbital purpura (racoon eyes), and restrictive cardiomyopathy. Congo red staining of the endomyocardial biopsy shows apple-green birefringence under polarized light. Mass spectrometry-based proteomic analysis of the amyloid deposits would be most informative for which reason?
11. A 6-month-old boy presents with recurrent Pseudomonas aeruginosa and Staphylococcus aureus infections, a painful lip ulcer, partial oculocutaneous albinism, and nystagmus. Peripheral blood smear shows giant granules in neutrophils. Which pathological mechanism underlies this immunodeficiency?
12. A patient with ankylosing spondylitis is treated with adalimumab. Paradoxically, she develops a new-onset pustular psoriasis. This exemplifies a reaction known as a 'paradoxical adverse effect of anti-TNF therapy.' Which cytokine pathway, upregulated when TNF is blocked, best explains TNF-blocker-induced psoriasis?
13. A 35-year-old woman with CREST syndrome (limited systemic sclerosis) is most likely to test positive for which specific autoantibody, and what is its clinical correlation?
14. A 40-year-old patient develops recurrent sinopulmonary infections, lymphoma, and has very low serum IgG, IgA, and IgM but normal number of B cells in peripheral blood. Germinal centers are absent on lymph node biopsy. This immunodeficiency is MOST likely:
15. In secondary (AA) amyloidosis, the amyloid fibrils are derived from SAA (serum amyloid A), an acute phase reactant. SAA is primarily synthesized by:
16. Seronegative antiphospholipid syndrome (APS) is characterized by thrombosis and pregnancy loss without detectable lupus anticoagulant, anticardiolipin, or anti-β2GPI antibodies. A newly described antigen in seronegative APS is:
17. A patient with AA amyloidosis secondary to rheumatoid arthritis has the amyloid protein derived from serum amyloid A (SAA). Which organ shows the most characteristic 'lardaceous' gross appearance on autopsy and demonstrates positive staining with Congo red showing apple-green birefringence?
18. X-linked agammaglobulinemia (Bruton disease) results from BTK (Bruton tyrosine kinase) mutations. BTK is essential for which specific developmental checkpoint in B-cell maturation?
19. A patient develops immune thrombocytopenic purpura (ITP). The primary mechanism of platelet destruction involves antiplatelet IgG antibodies binding to GPIIb/IIIa. These opsonized platelets are primarily destroyed in which location and by which mechanism?
20. A patient with IgA nephropathy has worsening proteinuria. Galactose-deficient IgA1 (Gd-IgA1) is considered the central pathogenic molecule. Why does Gd-IgA1 lead to glomerular injury?
21. AL amyloidosis is derived from immunoglobulin light chains. In contrast, AA amyloidosis is derived from which serum precursor protein?
22. X-linked agammaglobulinemia (XLA) results from BTK gene mutation. The developmental block in B-cell maturation in XLA occurs at which stage?
23. In systemic lupus erythematosus, aberrant clearance of apoptotic cells is a key mechanism generating nuclear autoantigens. Which complement pathway deficiency is most strongly associated with susceptibility to SLE?
24. A 30-year-old man with a known hereditary immunodeficiency develops recurrent pneumonia with Streptococcus pneumoniae and Haemophilus influenzae (encapsulated bacteria) but NOT recurrent viral or fungal infections. Serum immunoglobulins are markedly reduced (IgG <1 g/L, IgM undetectable, IgA undetectable) but T-cell count is normal. Which genetic defect is the underlying cause?
25. A 68-year-old man with a 10-year history of rheumatoid arthritis develops proteinuria (4 g/day), hepatomegaly, and renal insufficiency. Rectal biopsy shows Congo red positive material with apple-green birefringence under polarized light. Which specific amyloid fibril protein is responsible in this secondary systemic amyloidosis?
26. A 25-year-old woman develops serum sickness 8 days after receiving horse antithymocyte globulin (ATG) for aplastic anemia. She develops fever, urticaria, arthralgias, and proteinuria. The immunopathological mechanism involves:
27. A newborn girl is found to have absent thymic shadow on chest X-ray, hypocalcemia (due to absence of parathyroid glands), and conotruncal cardiac defects (truncus arteriosus). T-cell count is severely reduced, but B-cells are normal. Serum immunoglobulins are low (due to absent T-helper function). Which embryological structure failed to develop properly?
28. A 45-year-old woman with SLE develops diffuse proliferative lupus nephritis (Class IV). The key immunological mechanism driving glomerular injury is:
29. In AL (primary) amyloidosis, the amyloid precursor protein is:
30. A child presents with recurrent pyogenic infections, partial albinism, and peripheral neuropathy. Neutrophils show giant granules on peripheral smear. The molecular defect in Chédiak-Higashi syndrome involves:
31. Goodpasture syndrome presents with pulmonary hemorrhage and rapidly progressive glomerulonephritis. The target antigen for the anti-GBM antibodies is specifically:
32. A 3-year-old boy has severe, life-threatening infections with encapsulated bacteria, fungi, and Pneumocystis jirovecii. Flow cytometry shows absent T and B lymphocytes with NK cells present. This pattern is most consistent with:
33. In systemic lupus erythematosus (SLE), defective clearance of apoptotic cells is a key pathogenic mechanism. Which complement protein deficiency is most strongly linked to the development of SLE, and why?
34. A 45-year-old with a 10-year history of ankylosing spondylitis develops slowly progressive proteinuria and renal impairment. Renal biopsy shows Congo red-positive deposits in glomeruli and interstitium with apple-green birefringence under polarized light. Immunohistochemistry identifies the amyloid as AA type. The specific serum precursor protein is:
35. A 6-month-old male infant has severe recurrent infections with gram-negative and gram-positive organisms, fungi, and opportunistic pathogens. He has profound lymphopenia with absence of T cells, B cells, and NK cells. Adenosine deaminase (ADA) activity is markedly reduced. The cytotoxic metabolite accumulating in ADA deficiency that is particularly toxic to lymphocytes is:
36. Immunofluorescence of a skin biopsy from a patient with pemphigus vulgaris shows intercellular IgG deposits in the epidermis. The autoantibody target antigen is desmoglein 3 (Dsg3). At the molecular level, the mechanism by which anti-Dsg3 antibodies cause acantholysis involves:
37. Serum amyloid A (SAA)-derived amyloid (AA amyloidosis) differs from AL amyloidosis in its precursor protein and clinical associations. Which statement about AA amyloidosis is MOST ACCURATE?
38. Wiskott-Aldrich syndrome (WAS) is caused by mutation in the WASP gene encoding the Wiskott-Aldrich syndrome protein. WASP's primary function is:
39. In SLE pathogenesis, the failure to clear apoptotic cells and nuclear debris is central. The molecule MOST responsible for impaired clearance of apoptotic nuclear material in SLE is:
40. A 45-year-old woman with rheumatoid arthritis undergoes fat pad biopsy showing amyloid deposits that stain with Congo red and show apple-green birefringence under polarized light. Mass spectrometry of the deposits identifies SAA-derived peptides. What is the correct amyloid type, precursor protein, and associated clinical context in this scenario?
41. A 6-month-old boy presents with recurrent bacterial infections (Staphylococcus, Pneumococcus) and a profound absence of all peripheral blood B lymphocytes. Serum immunoglobulins of all isotypes are undetectable. T-cell numbers and function are normal. Genetic analysis reveals a hemizygous loss-of-function mutation in BTK. What is the most specific molecular mechanism by which BTK deficiency arrests B-cell development?
42. Regulatory T cells (Tregs) marked by FOXP3 maintain peripheral tolerance. In which of the following mechanisms do Tregs most directly suppress effector T-cell-mediated autoimmunity?
43. In systemic light chain (AL) amyloidosis, the amyloid fibrils are derived from immunoglobulin light chains. Kappa or lambda light chains can form fibrils, but lambda chains are overrepresented. The serum/urine biomarker most specific for monitoring AL amyloidosis treatment response is:
44. A patient with DiGeorge syndrome (22q11.2 deletion) lacks thymic tissue. The primary immunological defect expected is:
45. A 55-year-old woman with rheumatoid arthritis develops reactive (AA) amyloidosis. The amyloid A protein is derived from which serum precursor, and what is the pathological trigger for its overproduction?
46. A patient with long-standing type 2 diabetes develops cardiac dysfunction. Autopsy shows extensive amyloid deposits in the cardiac interstitium. Mass spectrometry of the amyloid identifies ATTR (transthyretin) protein. Which fibril form of ATTR is most likely responsible given this clinical context?
47. A patient develops haemolysis, renal failure and thrombocytopenia after receiving a blood transfusion. The direct Coombs test (DAT) is strongly positive. This represents which hypersensitivity type and which complement pathway is primarily responsible for intravascular haemolysis?
48. A 4-year-old boy with a history of recurrent Staphylococcal and Aspergillus infections since infancy is found to have a negative dihydrorhodamine (DHR) flow cytometry test. NBT (nitroblue tetrazolium) test is negative. Genetic testing reveals a mutation in the CYBB gene (encoding gp91phox). What is the fundamental mechanism of the immunodeficiency?
49. A patient with systemic lupus erythematosus (SLE) has high-titre anti-dsDNA antibodies detected by Crithidia luciliae immunofluorescence. Which mechanism directly explains why anti-dsDNA antibodies are highly specific for SLE compared to other ANA-positive conditions?
50. Serum amyloid A (SAA)-derived amyloid AA is the systemic amyloid deposited in reactive (secondary) amyloidosis. SAA is an acute phase protein. Which statement about the mechanism of AA amyloid formation is MOST accurate?
51. A 28-year-old man with recurrent severe bacterial infections (Streptococcus pneumoniae, Haemophilus influenzae) since infancy has absent serum immunoglobulins of all isotypes and absent B cells on flow cytometry. T-cell counts and function are normal. BTK gene mutation is confirmed. Which immunodeficiency is this, and why does it spare T-cell immunity?
52. In systemic lupus erythematosus (SLE), defective clearance of apoptotic cellular debris is a key upstream event driving autoimmunity. Which complement component deficiency most strongly predisposes to SLE by this mechanism?
53. A 60-year-old man with long-standing rheumatoid arthritis develops nephrotic syndrome. Renal biopsy shows amorphous eosinophilic material in the glomerular mesangium and vessel walls that is Congo red positive with apple-green birefringence under polarized light. Immunohistochemistry is positive for SAA protein. The amyloid type and classification per WHO 2022 amyloid nomenclature is:
54. In common variable immunodeficiency (CVID), the most characteristic immunological defect is:
55. CTLA-4 (CD152) and PD-1 (CD279) are two distinct immune checkpoint molecules targeted by current cancer immunotherapy. Their molecular mechanisms of T-cell inhibition differ in that:
56. A 30-year-old woman develops systemic lupus erythematosus. Renal biopsy reveals proliferative lupus nephritis (class III/IV). The dominant immunopathological mechanism of glomerular injury in proliferative lupus nephritis is:
57. A 65-year-old man with multiple myeloma develops nephrotic syndrome. Renal biopsy shows eosinophilic amyloid deposits that are apple-green birefringent under polarized light after Congo red staining. Mass spectrometry identifies the amyloid fibrils as AL-lambda type. What is the composition of AL amyloid?
58. A male infant with recurrent bacterial and fungal infections has absent T cells, absent B cells, and absent NK cells on flow cytometry. Enzyme assay shows absent adenosine deaminase (ADA) activity. The pathophysiology involves accumulation of which toxic metabolite in lymphoid progenitors?
59. Transthyretin (TTR) amyloidosis (ATTR) causes restrictive cardiomyopathy. Val122Ile (V142I in new nomenclature) is the most common pathogenic variant in Black patients. What is the mechanism by which mutant TTR forms amyloid fibrils different from wild-type TTR?
60. A 3-year-old boy has recurrent pyogenic infections with Staphylococcus aureus and Aspergillus. Neutrophils show normal chemotaxis but fail to kill intracellular organisms. NBT (nitroblue tetrazolium) test is negative. Flow cytometry of CD18 and CD11b expression is normal. Which gene defect is most likely responsible?
61. Serum AA amyloidosis complicating chronic inflammatory disease (rheumatoid arthritis, FMF) involves deposition of AA protein derived from which serum precursor, and which organ distribution is most characteristic?
62. Serum amyloid A (SAA)-derived amyloid (AA amyloidosis) deposits preferentially in which organs and in which pattern on Congo red staining?
63. In X-linked agammaglobulinemia (Bruton's disease), the molecular defect is absence of functional BTK (Bruton's tyrosine kinase), which blocks B-cell development at the:
64. In Graves' disease, TSH receptor antibodies (TRAb) cause hyperthyroidism by acting as Type II hypersensitivity antibodies. Their correct classification is:
65. A patient develops thrombocytopenia and thrombosis after heparin therapy. Platelet factor 4 (PF4)-heparin complex antibodies activate platelets via FcγRIIA receptor. Which hypersensitivity type is heparin-induced thrombocytopenia (HIT)?
66. A patient with chronic renal failure on long-term hemodialysis develops carpal tunnel syndrome and arthropathy. Congo red staining of the joint biopsy shows apple-green birefringence. What is the amyloid fibril protein responsible?
67. A 20-year-old man presents with recurrent sinopulmonary infections, no lymphadenopathy, and absent tonsils. Peripheral blood B cells are absent; T cells are normal. Serum shows absent IgG, IgA, IgM. What is the MOST likely immunodeficiency?
68. A patient develops rigors, hypotension, and haemoglobinuria 30 minutes after starting a blood transfusion. The Coombs test is positive. This is an acute haemolytic transfusion reaction due to which type of hypersensitivity and which immunoglobulin class?
69. In systemic amyloidosis due to AL type (primary amyloidosis), the amyloid fibrils are derived from which precursor protein?
70. A 6-year-old boy has recurrent pyogenic infections with catalase-positive organisms (Staphylococcus aureus, Aspergillus, Klebsiella) since infancy, with lymphadenitis and hepatosplenomegaly. NBT (nitroblue tetrazolium) test is negative. The defect is in which enzyme complex?
71. A renal biopsy from a patient with long-standing rheumatoid arthritis shows amyloid deposits that stain positively with Congo red and demonstrate apple-green birefringence under polarised light. Mass spectrometry would most likely identify the amyloid protein as:
72. A 25-year-old woman receives a penicillin injection and develops urticaria, bronchospasm, and hypotension within minutes. Which IgE-mediated cell type degranulates to cause these immediate hypersensitivity (Type I) manifestations?
73. Secondary (AA) amyloidosis most commonly complicates chronic inflammatory diseases. The precursor serum protein that forms AA fibrils is:
74. A 6-month-old boy has recurrent bacterial infections but no viral infections. Immunoglobulins are absent in serum, but T-cell counts are normal. Lymph nodes show absent germinal centers. Peripheral blood B cells are absent. The MOST likely diagnosis is:
75. Which staining property BEST confirms amyloid deposits in a tissue section?
76. Goodpasture syndrome involves autoantibodies against which specific antigen in the glomerular basement membrane?
77. A 25-year-old woman is found to have AA amyloidosis complicating rheumatoid arthritis. The amyloid protein AA is derived from which circulating precursor protein?
78. A 20-year-old man has recurrent sino-pulmonary infections, absent tonsils, and profound reduction in all immunoglobulin classes. Flow cytometry shows absent CD19+ B cells but normal T cell numbers. The genetic defect in this condition involves:
79. A 55-year-old woman develops recurrent blistering of oral mucosa and skin. Biopsy shows intraepidermal acantholysis with tombstoning of basal cells. Direct immunofluorescence demonstrates IgG in an intercellular 'fish-net' or 'chicken-wire' pattern. The autoantigen targeted is:
80. A patient with Chédiak-Higashi syndrome presents with recurrent pyogenic infections, partial oculocutaneous albinism, and peripheral neuropathy. Peripheral blood smear shows neutrophils with giant azurophilic granules. The molecular defect in this condition affects:
81. In systemic amyloidosis (AA type), the serum precursor protein that deposits as amyloid fibrils is derived from which acute-phase reactant?
82. A patient with Bruton X-linked agammaglobulinaemia has recurrent encapsulated bacterial infections. The molecular defect is in Bruton tyrosine kinase (BTK), which blocks B-cell maturation at which stage?
83. In Type III hypersensitivity (immune complex-mediated), the key complement-derived factor responsible for neutrophil recruitment to sites of immune complex deposition is:
84. A patient with SLE has a positive ANA, anti-dsDNA antibody, and low C3/C4. The Congo red stain of a renal biopsy would show apple-green birefringence ONLY if:
85. A 30-year-old woman with SLE has recurrent arterial thromboses and elevated anti-phospholipid antibodies. These antibodies cause thrombosis primarily by:
86. Secondary (AA) amyloidosis deposits which precursor protein derived from the acute-phase response?
87. In type I (immediate) hypersensitivity, the sensitisation phase involves:
88. DiGeorge syndrome results from failure of development of the third and fourth pharyngeal pouches, causing thymic aplasia. The predominant immunological defect is:
89. A 25-year-old receives penicillin and develops urticaria, bronchospasm, and hypotension within minutes. The mechanism is IgE-mediated mast cell degranulation. The vasoactive mediator released first (preformed, from granules) causing immediate vasodilation is:
90. A 30-year-old woman with SLE has anti-dsDNA and anti-Sm antibodies. The mechanism of lupus nephritis involves deposition of immune complexes, activating complement. The complement fragment directly responsible for recruiting neutrophils and monocytes is:
91. A 65-year-old man with long-standing multiple myeloma develops progressive nephrotic syndrome. Congo red staining of renal biopsy shows apple-green birefringence under polarized light in the mesangium and vessel walls. The amyloid protein in this clinical context is:
92. A boy presents at 6 months with severe bacterial and fungal infections. Lymph nodes are absent. Serum immunoglobulins are undetectable. Peripheral blood shows no B cells and no T cells. The most likely diagnosis is:
93. In Goodpasture syndrome, the autoantibody targets a specific domain of type IV collagen. The domain targeted is the:
94. A 50-year-old woman presents with xerophthalmia, xerostomia, and bilateral parotid enlargement. Minor salivary gland biopsy shows periductal lymphocytic infiltration. The most specific autoantibody associated with primary Sjogren syndrome is:
95. In type III (immune complex) hypersensitivity, the Arthus reaction is a localized form. In the Arthus reaction, the antibody class that forms precipitating immune complexes leading to complement activation is:
96. A 3-year-old boy has recurrent sinopulmonary infections since 6 months of age, absent tonsils, and undetectable immunoglobulins. B cells are absent but T cells and NK cells are normal. Genetic testing shows a BTK mutation. The defective pathway is:
97. AA amyloidosis (reactive systemic amyloidosis) is most commonly associated with which underlying condition?
98. AA amyloidosis (reactive systemic amyloidosis) is composed of amyloid A protein derived from which serum precursor?
99. In systemic lupus erythematosus (SLE), the predominant mechanism by which nuclear antigens become accessible to the immune system involves defective clearance of which cellular process?
100. A 6-month-old male infant has recurrent bacterial and fungal infections, absent lymph nodes and tonsils, and no thymic shadow on chest X-ray. Lymphocyte count is markedly low with absent T, B, and NK cells. The most likely diagnosis is:
101. In AL amyloidosis, the amyloid fibrils are derived from which precursor protein?
102. In DiGeorge syndrome (22q11.2 deletion), the primary immunological defect is:
103. Amyloid deposits stain with Congo red and show apple-green birefringence under polarized light. Chemically, amyloid fibrils share which structural property regardless of their precursor protein?
104. In autoimmune hemolytic anemia (AIHA) associated with Mycoplasma pneumoniae infection, the responsible antibodies are:
105. In systemic lupus erythematosus (SLE), wire-loop lesions in glomeruli represent:
106. AL amyloidosis differs from AA amyloidosis in that AL amyloid fibrils are derived from:
107. A patient with systemic lupus erythematosus has antibodies to double-stranded DNA (anti-dsDNA). The primary mechanism by which these antibodies cause glomerulonephritis is:
108. Serum amyloid P component (SAP) is present in all types of amyloid deposits. Its histochemical significance is that it:
109. A boy presents at age 6 months with recurrent Pneumocystis pneumonia and failure to thrive. T cell count is profoundly low; B cells are also absent. Adenosine deaminase (ADA) enzyme activity is absent in RBCs. The mechanism of lymphocyte death in ADA-SCID is:
110. In Type II hypersensitivity reactions, tissue injury can occur by which three mechanisms?
111. A 35-year-old woman with rheumatoid arthritis develops proteinuria. Renal biopsy shows apple-green birefringence on Congo red under polarized light. The deposited protein subunit is most likely:
112. A 6-month-old boy has recurrent severe bacterial infections, no tonsils, absent B cells (CD19−) on flow cytometry, and undetectable immunoglobulins. T-cell count is normal. The most likely diagnosis and affected gene are:
113. Serum protein electrophoresis in nephrotic syndrome (minimal change disease) typically shows:
114. A 25-year-old woman develops urticaria and bronchoconstriction 15 minutes after a penicillin injection. Positive skin testing to penicillin was noted previously. The mechanism is:
115. Goodpasture syndrome involves autoantibodies against which specific antigen, and what hypersensitivity type is this?
116. A 55-year-old man with rheumatoid arthritis develops progressively enlarging kidneys with proteinuria. Renal biopsy stained with Congo red under polarized light shows apple-green birefringence in the glomeruli and arterioles. Immunohistochemistry confirms SAA protein deposits. This form of amyloidosis is classified as:
117. In systemic lupus erythematosus (SLE), the defective clearance of apoptotic cellular debris is central to pathogenesis. Which serum protein, when deficient, is most strongly associated with increased susceptibility to SLE due to impaired clearance of apoptotic cells?
118. A 25-year-old man with recurrent pyogenic infections by encapsulated organisms (Streptococcus pneumoniae, Haemophilus influenzae) since infancy is found to have absent B cells and profoundly low immunoglobulins of all isotypes. T cells are normal. What is the molecular defect in X-linked agammaglobulinemia (Bruton's disease)?
119. A patient with systemic lupus erythematosus has antibodies to double-stranded DNA and Smith antigen. The primary mechanism of glomerular injury in lupus nephritis is:
120. In AL amyloidosis (primary amyloidosis), the fibril precursor protein is:
121. DiGeorge syndrome results from a microdeletion at chromosome 22q11.2 causing failure of development of the third and fourth pharyngeal pouches. The primary immunological consequence is:
122. Congo red staining of an amyloid-laden tissue viewed under polarized light shows which characteristic finding?
123. A 25-year-old develops urticaria, angioedema, and bronchospasm within minutes of a penicillin injection. This reaction is mediated by:
124. A 45-year-old woman with long-standing rheumatoid arthritis develops progressive nephropathy. Renal biopsy shows Congo red-positive deposits in the mesangium and vessel walls that show apple-green birefringence under polarized light. The amyloid protein most likely responsible is:
125. DiGeorge syndrome results from failure of development of the 3rd and 4th pharyngeal pouches. The primary immunological defect is:
126. A 35-year-old man with HIV (CD4 count 40 cells/μL) develops rapidly progressive dementia, aphasia, and visual field defects. MRI shows multiple non-enhancing white matter lesions without mass effect. CSF PCR detects JC virus. What is the condition, and what is the pathological mechanism of demyelination?
127. A 25-year-old man has recurrent pyogenic infections with Staphylococcus, Streptococcus, and Klebsiella since infancy, along with partial albinism and peripheral neuropathy. Peripheral blood neutrophils show giant cytoplasmic granules. The condition is:
128. AA amyloidosis (secondary amyloidosis) complicates chronic inflammatory diseases such as rheumatoid arthritis. The amyloid fibrils in AA amyloidosis are derived from which serum precursor protein?
129. In DiGeorge syndrome, thymic aplasia results in profound deficiency of which immune cell type, and what is the chromosome involved?
130. Serum protein electrophoresis in a patient with amyloidosis shows a narrow 'M-spike' in the gamma-globulin region. Congo red staining of a rectal biopsy shows apple-green birefringence under polarised light. What structural property of amyloid fibrils produces this characteristic birefringence?
131. The Arthus reaction is a localized Type III hypersensitivity reaction. The key pathological sequence is:
132. In systemic lupus erythematosus (SLE), anti-dsDNA antibodies contribute to glomerulonephritis primarily by:
133. A patient with reactive (secondary, AA) amyloidosis has recurrent chronic infections. The amyloid protein deposited is derived from which precursor?
134. DiGeorge syndrome (22q11.2 deletion) results in which combination of immunological defects?
135. A 22-year-old medical student receives penicillin and 72 hours later develops fever, skin rash, and lymphadenopathy. Complement levels (C3, C4) are low. This reaction is best classified as:
136. Systemic (AL) amyloidosis most commonly results from which precursor protein, and what is the underlying plasma cell disorder?
137. A 4-year-old boy with recurrent pneumonias and absent tonsils is found to have undetectable serum immunoglobulins of all classes. A mutation in which gene is the most likely cause of this X-linked condition?
138. A 35-year-old woman with lupus erythematosus has antibodies against double-stranded DNA and Smith antigen. Anti-dsDNA titers are useful for monitoring disease because:
139. In systemic lupus erythematosus (SLE), the wire-loop lesion on light microscopy of renal biopsy corresponds to which WHO/ISN-RPS class of lupus nephritis?
140. Primary (AL) amyloidosis has precursor protein derived from immunoglobulin light chains. Secondary (AA) amyloidosis has precursor protein serum amyloid A (SAA), an acute phase reactant. In AA amyloidosis, SAA is converted to amyloid A (AA) fibrils in which organ?
141. DiGeorge syndrome results from a 22q11.2 deletion affecting pharyngeal pouch development. The immune defect is best characterized as:
142. In serum sickness (type III hypersensitivity), the immune complex deposition at vessel walls activates complement. Which complement fragment generated during this process is most responsible for mast cell degranulation and increased vascular permeability?
143. A 19-year-old man develops urticaria, bronchospasm, and hypotension within 10 minutes of receiving penicillin intravenously. He was treated with penicillin for a skin infection 3 months ago without incident. Which immunological mechanism is responsible for his current reaction?
144. A 35-year-old woman with a 2-year history of fatigue, malar rash, photosensitivity, and joint pain has an ANA titer of 1:640 (speckled pattern). Anti-dsDNA and anti-Smith antibodies are positive. Urinalysis shows 2+ protein and RBC casts. Renal biopsy shows glomerular immune complex deposits in the mesangium and subendothelial space with granular (lumpy-bumpy) immunofluorescence for IgG and C3. What is the PRIMARY mechanism of renal injury?
145. An 80-year-old man with longstanding multiple myeloma develops macroglossia, carpal tunnel syndrome, and nephrotic syndrome. Renal biopsy shows eosinophilic amorphous deposits in the mesangium and along capillary walls that exhibit apple-green birefringence under polarized light after Congo red staining. Which protein is MOST likely forming these deposits?
146. A 45-year-old woman presents with proximal muscle weakness, difficulty swallowing, and heliotrope rash around the eyelids. Serum CK is markedly elevated. Muscle biopsy shows perifascicular atrophy with CD4+ T cell and B cell infiltrates predominantly in perimysial vessels. Which antibody, if positive, would be MOST specific for this diagnosis?
147. A 25-year-old farmer develops wheezing and dyspnea 4–6 hours after entering a hay barn. He has no immediate reaction on entering. Serum precipitins against thermophilic actinomycetes are positive. Lung biopsy shows non-caseating granulomas and lymphocytic alveolitis. This is BEST classified as:
148. A 30-year-old woman presents with butterfly rash, arthritis, serositis, and renal involvement. ANA is positive at 1:640. Which autoantibody pattern carries the highest specificity for systemic lupus erythematosus (SLE) AND correlates with disease activity and lupus nephritis?
149. A 4-year-old boy has had recurrent pneumococcal sepsis, meningitis at age 2, and H. influenzae pneumonia. Immunoglobulin levels show IgG 180 mg/dL, IgA undetectable, IgM undetectable. B cells are absent on flow cytometry. T-cell counts are normal. The molecular defect most likely involves:
150. A 35-year-old man undergoes cadaveric renal transplant. On day 3 post-transplant, he develops sudden oliguria, graft tenderness, and fever. Biopsy shows dense neutrophilic infiltration of glomeruli and vessels with fibrinoid necrosis but no significant lymphocytic infiltrate. DSA (donor-specific antibodies) are detected at high titer. This rejection is BEST classified as:
151. AA amyloid (secondary/reactive amyloidosis) is composed of which protein, and in which chronic condition is it most classically deposited?
152. A 55-year-old man with long-standing ankylosing spondylitis develops nephrotic syndrome. Renal biopsy with Congo red staining shows apple-green birefringence under polarized light. Electron microscopy shows randomly arranged 8–12 nm fibrils. Which feature would distinguish AL from AA amyloidosis in this biopsy specimen?
153. DiGeorge syndrome results from a microdeletion at chromosome 22q11.2. The primary immunologic consequence is:
154. A 45-year-old woman with primary Sjögren syndrome has a positive anti-Ro (SS-A) antibody. She becomes pregnant. Which fetal/neonatal complication is most directly attributable to transplacental passage of this antibody?
155. In Type II hypersensitivity, tissue damage can occur through multiple effector mechanisms. Which of the following correctly pairs the antibody target with the disease mechanism in Goodpasture syndrome?
156. Hereditary angioedema (HAE) presents with recurrent non-pruritic, non-pitting soft-tissue swelling without urticaria. The underlying defect responsible for bradykinin accumulation is:
157. Scleroderma (systemic sclerosis) is characterised by fibrosis. Anti-topoisomerase I (Scl-70) antibodies are associated with which subtype, and anti-centromere antibodies with which subtype?
158. DiGeorge syndrome results from a 22q11.2 deletion affecting pharyngeal pouch development. The primary immunological defect is:
159. In chronic rejection of a transplanted kidney, the predominant mechanism of graft damage (distinct from acute rejection) is:
160. Which serum protein is used as a biochemical marker of amyloid deposition activity in AA amyloidosis, as it reflects the acute phase reactant that serves as the precursor protein?