Immunopathology — MCQs

A 23-year-old woman develops a skin rash after prolonged sun exposure and has a malar rash on physical examination. Laboratory studies show a positive ANA test result with a titer of 1:1024 and a "rim" pattern, along with a positive anti-double-stranded DNA test. Her hemoglobin is 12.1 g/dL, hematocrit is 35.5%, MCV is 89 mm 3, platelet count is 109,000/mm 3, and WBC count is 4500/mm 3. Which of the following findings is most likely to be shown by a WBC differential count?

Q325Easy

Serum sickness is which type of hypersensitivity reaction?

Q326Easy

Which of the following complement factors is present in the final common terminal pathway?

Q327Medium

Antihistone antibodies are detectable in which of the following conditions?

Q328Medium

Which of the following is an example of Type IV hypersensitivity?

Q329Easy

Chediak-Higashi syndrome is characterized by which of the following defects?

Q330Easy

Chediak-Higashi syndrome is characterized by which of the following defects?

Immunopathology Indian Medical PG Practice Questions and MCQs

Question 321: NADPH oxidase deficiency causes impaired immunity. Which of the following processes is affected?

A. Chediak-Higashi syndrome
B. Chronic granulomatous disease (Correct Answer)
C. Leukocyte adhesion defect type 1
D. Leukocyte adhesion defect type 2

Explanation: ### Explanation **Correct Answer: B. Chronic Granulomatous Disease (CGD)** **Mechanism:** The primary defect in **Chronic Granulomatous Disease (CGD)** is a deficiency in the **NADPH oxidase enzyme complex** (specifically the *gp91phox* subunit in the X-linked form). This enzyme is responsible for the "respiratory burst," which converts molecular oxygen into superoxide radicals ($O_2^-$). These radicals are essential for the production of reactive oxygen species (ROS) like hydrogen peroxide ($H_2O_2$) and hypochlorous acid ($HOCl$) within phagolysosomes. Without NADPH oxidase, phagocytes (neutrophils and macrophages) can ingest bacteria but cannot kill them, leading to persistent infections and the formation of **granulomas**. **Analysis of Incorrect Options:** * **A. Chediak-Higashi Syndrome:** This is a defect in **vesicle trafficking (LYST gene)**. It results in the failure of phagosome-lysosome fusion and is characterized by giant cytoplasmic granules in neutrophils [1]. * **C. Leukocyte Adhesion Defect (LAD) Type 1:** Caused by a deficiency of **CD18 (integrin $\beta$2 chain)**. It leads to impaired firm adhesion of leukocytes to the endothelium, resulting in delayed umbilical cord separation and absent pus formation. * **D. Leukocyte Adhesion Defect (LAD) Type 2:** Caused by a defect in **Sialyl-Lewis X**, leading to impaired "rolling" of leukocytes due to lack of selectin binding. **NEET-PG High-Yield Pearls:** * **Inheritance:** Most common form is **X-linked recessive** (gp91phox mutation). * **Organisms:** Patients are highly susceptible to **Catalase-positive organisms** (e.g., *Staphylococcus aureus, Aspergillus, Nocardia, Serratia*) because these organisms neutralize their own $H_2O_2$, leaving the phagocyte with no ROS to use for killing. * **Diagnostic Test:** The gold standard is the **Dihydrorhodamine (DHR) flow cytometry test** (replaces the older Nitroblue Tetrazolium/NBT slide test). * **Clinical Sign:** Recurrent skin infections, abscesses, and granulomatous inflammation of the GI/GU tract. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, pp. 245-246.

Question 322: Which of the following immunoglobulins is absent in Ataxia telangiectasia?

A. IgG
B. IgM
C. IgA (Correct Answer)
D. IgD

Explanation: ### Explanation **Ataxia-Telangiectasia (AT)** is an autosomal recessive multisystem disorder caused by a mutation in the **ATM (Ataxia-Telangiectasia Mutated) gene** on chromosome 11 [1]. This gene is responsible for repairing double-stranded DNA breaks. #### Why IgA is the Correct Answer: The hallmark of AT is a combined immunodeficiency affecting both humoral and cellular immunity. The most characteristic laboratory finding is a **selective deficiency of IgA**, which occurs in approximately 70% of patients [1]. This occurs because the defective DNA repair mechanism impairs **class-switch recombination**, the process required to switch from IgM to other isotypes like IgA or IgE. #### Analysis of Incorrect Options: * **IgG:** While some subclasses of IgG (like IgG2) may be decreased, total IgG is usually normal or only mildly reduced compared to the profound absence of IgA. * **IgM:** IgM levels are typically **normal or elevated**. Since IgM is the first antibody produced and does not require class-switching, it remains unaffected by the ATM mutation. * **IgD:** IgD deficiency is not a clinical feature of AT and does not carry diagnostic significance for this condition. #### High-Yield Clinical Pearls for NEET-PG: * **Clinical Triad:** 1. Progressive cerebellar **ataxia** (early childhood), 2. Oculocutaneous **telangiectasia** (conjunctival "bloodshot" eyes), 3. Recurrent sinopulmonary infections [1]. * **Diagnostic Marker:** Elevated **Alpha-fetoprotein (AFP)** levels after age 2 are highly suggestive of AT. * **Malignancy Risk:** Patients have a 100x higher risk of developing lymphomas and leukemias due to genomic instability [1]. * **Radiosensitivity:** Patients are hypersensitive to **ionizing radiation** (X-rays/CT scans), which causes catastrophic DNA damage. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, pp. 250-251.

Question 323: Lack of leukocyte adhesion molecules (LAM) is associated with which of the following?

A. Delayed separation of the umbilical cord (Correct Answer)
B. Normal leukocyte chemotaxis
C. Complement opsonization
D. Neutropenia

Explanation: This question tests your knowledge of **Leukocyte Adhesion Deficiency (LAD) Type 1**, an autosomal recessive disorder characterized by a defect in the **CD18 subunit of β2-integrins** (LFA-1, Mac-1). [1] ### Why the Correct Answer is Right **Delayed separation of the umbilical cord** (typically >30 days) is the classic clinical hallmark of LAD-1. Under normal physiological conditions, the umbilical cord undergoes necrosis, which triggers an inflammatory response. Neutrophils must adhere to the vascular endothelium and emigrate into the tissue to digest the cord stump. In LAD, the lack of adhesion molecules (integrins) prevents neutrophils from exiting the bloodstream [1], [2]. Consequently, the cord does not undergo the necessary enzymatic degradation, leading to delayed separation. ### Why the Other Options are Wrong * **B. Normal leukocyte chemotaxis:** This is incorrect because chemotaxis is severely **impaired**. Since leukocytes cannot adhere to or crawl along the endothelium (diapedesis), they cannot reach the site of injury or infection despite the presence of chemoattractants [3]. * **C. Complement opsonization:** This is incorrect. While the defect involves the Mac-1 receptor (CR3), which binds iC3b, the primary pathology in LAD is a failure of **adhesion and migration**, not a generalized failure of the complement system itself. * **D. Neutropenia:** This is incorrect. Patients with LAD actually present with **marked peripheral leukocytosis/neutrophilia**, especially during infections. Because neutrophils cannot leave the circulation to enter tissues, they remain trapped in the blood vessels. ### High-Yield Clinical Pearls for NEET-PG * **Triad of LAD-1:** Delayed umbilical cord separation, recurrent bacterial infections (skin/mucosa) without pus formation, and persistent neutrophilia. * **The "Cold" Abscess:** Infections in LAD are characterized by a **lack of pus** (absent neutrophils at the site of infection). * **Molecular Defect:** LAD-1 is a defect in **Integrins** (CD18) [2]; LAD-2 is a defect in **Selectin ligands** (Sialyl-Lewis X). **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Inflammation and Repair, pp. 87-89. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Inflammation and Repair, p. 87. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Migration in the tissues toward a chemotactic stimulus, pp. 86-87.

Question 324: A 23-year-old woman develops a skin rash after prolonged sun exposure and has a malar rash on physical examination. Laboratory studies show a positive ANA test result with a titer of 1:1024 and a "rim" pattern, along with a positive anti-double-stranded DNA test. Her hemoglobin is 12.1 g/dL, hematocrit is 35.5%, MCV is 89 mm 3, platelet count is 109,000/mm 3, and WBC count is 4500/mm 3. Which of the following findings is most likely to be shown by a WBC differential count?

A. Basophilia
B. Eosinophilia
C. Monocytosis (Correct Answer)
D. Neutrophilia

Explanation: ### Explanation **Clinical Diagnosis: Systemic Lupus Erythematosus (SLE)** The patient presents with classic features of SLE: photosensitivity, a malar rash, a high-titer ANA with a ""rim"" (peripheral) pattern, and positive anti-dsDNA antibodies. The peripheral pattern of ANA is highly specific for antibodies against double-stranded DNA, which is a hallmark of SLE. **Why Monocytosis is the Correct Answer:** In the context of SLE, hematologic abnormalities are common and are included in the ACR diagnostic criteria. While **lymphopenia** (low lymphocyte count) is the most characteristic white blood cell finding in SLE, the question asks what a differential count would likely show among the provided options. * **Monocytosis** is frequently observed in patients with active SLE. This occurs because monocytes/macrophages are recruited to clear the increased load of apoptotic debris and immune complexes characteristic of the disease. Chronic inflammatory states often trigger a compensatory increase in monocytes. **Analysis of Incorrect Options:** * **A. Basophilia:** Typically associated with myeloproliferative neoplasms (e.g., CML) or immediate hypersensitivity reactions, not SLE. * **B. Eosinophilia:** Seen in allergic conditions, parasitic infections, or Churg-Strauss syndrome [1]. It is not a feature of SLE. * **D. Neutrophilia:** SLE usually presents with **neutropenia** (due to Type II hypersensitivity peripheral destruction) rather than neutrophilia. Neutrophilia in an SLE patient usually suggests a secondary bacterial infection or corticosteroid therapy [1]. **NEET-PG High-Yield Pearls:** * **ANA Patterns:** The **Rim (Peripheral) pattern** is highly specific for anti-dsDNA (SLE). The **Homogeneous pattern** is associated with anti-histone antibodies (Drug-induced Lupus). * **Hematology of SLE:** Look for ""Cytopenias""—specifically **Anemia of Chronic Disease**, **Thrombocytopenia**, and **Lymphopenia**. * **Most Specific Tests:** Anti-dsDNA and Anti-Smith (Anti-Sm) antibodies. Anti-dsDNA levels also correlate with disease activity and lupus nephritis. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 580-581.

Question 325: Serum sickness is which type of hypersensitivity reaction?

A. Type I
B. Type II
C. Type III (Correct Answer)
D. Type IV

Explanation: **Explanation:** **Serum sickness** is a classic example of **Type III Hypersensitivity** [1], which is mediated by the formation of **immune complexes** (antigen-antibody complexes) [3]. When a large amount of foreign antigen (e.g., horse serum, certain drugs like penicillin) enters the bloodstream, the body produces antibodies (IgG or IgM). These antibodies bind to the circulating antigens, forming complexes that deposit in various tissues, particularly small blood vessels, joints, and kidneys [1], [2]. This deposition activates the **complement system**, leading to neutrophil recruitment and subsequent tissue damage (vasculitis, arthritis, and glomerulonephritis) [3]. **Analysis of Options:** * **Type I (Immediate):** Mediated by **IgE** antibodies and mast cell degranulation (e.g., Anaphylaxis, Asthma). Serum sickness involves IgG/IgM and complement, not IgE. * **Type II (Antibody-mediated):** Involves antibodies directed against antigens on **specific cell surfaces** or tissues (e.g., Autoimmune hemolytic anemia, Myasthenia gravis). Serum sickness involves *circulating* complexes, not fixed tissue antigens. * **Type IV (Delayed-type):** Mediated by **T-cells**, not antibodies (e.g., Mantoux test, Contact dermatitis). Serum sickness is an antibody-mediated process. **High-Yield NEET-PG Pearls:** * **Arthus Reaction:** The localized form of Type III hypersensitivity (e.g., post-vaccination swelling). Serum sickness is the **systemic** form [1]. * **Clinical Triad:** Fever, rash (urticaria), and arthralgia occurring 7–14 days after exposure [3]. * **Morphology:** Characterized by **Fibrinoid necrosis** of the vessel walls. * **Complement levels:** Typically **decreased** (C3, C4) due to consumption during the reaction. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, pp. 214-215. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, pp. 215-216. [3] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. (Basic Pathology) introduces the student to key general principles of pathology, both as a medical science and as a clinical activity with a vital role in patient care. Part 2 (Disease Mechanisms) provides fundamental knowledge about the cellular and molecular processes involved in diseases, providing the rationale for their treatment. Part 3 (Systematic Pathology) deals in detail with specific diseases, with emphasis on the clinically important aspects., pp. 172-173.

Question 326: Which of the following complement factors is present in the final common terminal pathway?

A. C4
B. C3
C. C5 (Correct Answer)
D. Factor B

Explanation: ### Explanation The complement system consists of three pathways (Classical, Alternative, and Lectin) that converge at the formation of **C3 convertase**. However, the **Terminal Pathway** (also known as the Membrane Attack Complex or MAC pathway) begins only after the cleavage of C5 [1]. **Why C5 is Correct:** The terminal pathway starts when **C5 convertase** cleaves **C5** into C5a and C5b [3]. C5b then serves as the anchor for the assembly of the remaining components: **C6, C7, C8, and C9** [1]. Together, these form the MAC (C5b-9), which creates pores in the target cell membrane, leading to osmotic lysis [1]. Therefore, C5 is the first component of the final common terminal pathway. **Analysis of Incorrect Options:** * **A. C4:** This is a component of the **Classical** and **Lectin** pathways [3]. It is involved in forming the C3 convertase (C4b2a) and is not part of the terminal sequence. * **B. C3:** This is the most abundant complement protein and the point where all pathways converge to initiate the amplification loop [1]. While essential, it precedes the terminal pathway [3]. * **D. Factor B:** This is a unique component of the **Alternative pathway**, required for the formation of the alternative C3 convertase (C3bBb). **High-Yield Clinical Pearls for NEET-PG:** * **C3 deficiency:** Most common complement deficiency; leads to recurrent pyogenic infections. * **C5-C9 deficiency:** Specifically predisposes individuals to recurrent **Neisseria** infections (meningitis and gonorrhea) because Neisseria species are highly sensitive to MAC-mediated lysis. * **Paroxysmal Nocturnal Hemoglobinuria (PNH):** Caused by a deficiency of DAF (CD55) and MIRL (CD59), which normally protect host cells from the terminal MAC complex [2]. * **Eculizumab:** A monoclonal antibody that targets **C5**, preventing the formation of the terminal pathway; used in treating PNH and atypical HUS. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Inflammation and Repair, pp. 99-100. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. (Basic Pathology) introduces the student to key general principles of pathology, both as a medical science and as a clinical activity with a vital role in patient care. Part 2 (Disease Mechanisms) provides fundamental knowledge about the cellular and molecular processes involved in diseases, providing the rationale for their treatment. Part 3 (Systematic Pathology) deals in detail with specific diseases, with emphasis on the clinically important aspects., pp. 163-164. [3] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. (Basic Pathology) introduces the student to key general principles of pathology, both as a medical science and as a clinical activity with a vital role in patient care. Part 2 (Disease Mechanisms) provides fundamental knowledge about the cellular and molecular processes involved in diseases, providing the rationale for their treatment. Part 3 (Systematic Pathology) deals in detail with specific diseases, with emphasis on the clinically important aspects., pp. 162-163.

Question 327: Antihistone antibodies are detectable in which of the following conditions?

A. CREST syndrome
B. Polyarteritis nodosa
C. Drug-induced lupus erythematosus (Correct Answer)
D. Intestinal lymphoma

Explanation: **Explanation:** **Antihistone antibodies** are the hallmark serological marker for **Drug-induced Lupus Erythematosus (DILE)**. In this condition, certain drugs (most commonly Hydralazine, Procainamide, and Isoniazid) alter the structure of chromatin, leading to the formation of antibodies against histone proteins. These antibodies are present in over **95% of DILE cases**, making them highly sensitive for the diagnosis. Unlike systemic lupus erythematosus (SLE), DILE rarely involves the kidneys or central nervous system and typically resolves upon discontinuation of the offending drug. **Analysis of Incorrect Options:** * **A. CREST Syndrome:** Characterized by **Anti-centromere antibodies** [1]. It is a localized form of systemic sclerosis (Calcinosis, Raynaud’s, Esophageal dysmotility, Sclerodactyly, Telangiectasia). * **B. Polyarteritis Nodosa (PAN):** A systemic necrotizing vasculitis of medium-sized arteries. It is classically **ANCA-negative** and strongly associated with Hepatitis B infection. * **D. Intestinal Lymphoma:** Associated with Celiac disease (Enteropathy-associated T-cell lymphoma) or chronic infections (IPSID), but not with antihistone antibodies. **High-Yield Clinical Pearls for NEET-PG:** 1. **Drug-Induced Lupus:** Most common drugs are **H**ydralazine, **I**soniazid, **P**rocainamide (**HIP**). 2. **SLE vs. DILE:** While antihistone antibodies are seen in both, the absence of **Anti-dsDNA** and **Anti-Sm** antibodies strongly favors a diagnosis of DILE. 3. **Screening Test:** ANA (Antinuclear Antibody) is positive in both SLE and DILE, usually showing a **homogeneous/diffuse** pattern [1]. 4. **Diffuse Systemic Sclerosis:** Associated with **Anti-Scl-70** (Anti-topoisomerase I) antibodies. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, p. 228.

Question 328: Which of the following is an example of Type IV hypersensitivity?

A. Serum sickness
B. Granulomatous reaction (Correct Answer)
C. Shwartzman reaction
D. Arthus reaction

Explanation: **Explanation:** **Type IV Hypersensitivity (Delayed-type Hypersensitivity)** is a cell-mediated immune response involving T-lymphocytes (CD4+ and CD8+) rather than antibodies [1]. **Why Option B is Correct:** A **Granulomatous reaction** is the classic example of Type IV hypersensitivity. It occurs when the immune system cannot eliminate a persistent antigen (e.g., *M. tuberculosis*). CD4+ T-cells (Th1) release cytokines like **IFN-gamma**, which activate macrophages, transforming them into epithelioid cells and multinucleated giant cells, eventually forming a granuloma [3]. This process typically takes 48–72 hours or longer to develop [4]. **Why the other options are incorrect:** * **Option A (Serum Sickness):** This is a systemic **Type III hypersensitivity** reaction caused by the deposition of circulating antigen-antibody (immune) complexes in tissues, leading to complement activation [1]. * **Option D (Arthus Reaction):** This is a localized **Type III hypersensitivity** reaction. It involves the formation of immune complexes at the site of antigen injection in a previously sensitized individual, leading to necrotizing vasculitis [1]. * **Option C (Shwartzman Reaction):** This is **not** a hypersensitivity reaction. It is a phenomenon of severe tissue necrosis and DIC (Disseminated Intravascular Coagulation) following two sequential exposures to bacterial endotoxins (LPS). **NEET-PG High-Yield Pearls:** * **Type IV Subtypes:** Remember that Contact Dermatitis and the Mantoux (Tuberculin) test are also prime examples of Type IV [2], [5]. * **Key Cytokine:** IFN-gamma is the most important cytokine for macrophage activation in granulomas [3]. * **Mnemonic for Hypersensitivity (ACID):** * **A**naphylactic (Type I) * **C**ytotoxic (Type II) * **I**mmune-Complex (Type III) * **D**elayed-type (Type IV) **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. (Basic Pathology) introduces the student to key general principles of pathology, both as a medical science and as a clinical activity with a vital role in patient care. Part 2 (Disease Mechanisms) provides fundamental knowledge about the cellular and molecular processes involved in diseases, providing the rationale for their treatment. Part 3 (Systematic Pathology) deals in detail with specific diseases, with emphasis on the clinically important aspects., pp. 173-174. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. (Basic Pathology) introduces the student to key general principles of pathology, both as a medical science and as a clinical activity with a vital role in patient care. Part 2 (Disease Mechanisms) provides fundamental knowledge about the cellular and molecular processes involved in diseases, providing the rationale for their treatment. Part 3 (Systematic Pathology) deals in detail with specific diseases, with emphasis on the clinically important aspects., pp. 174-175. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Inflammation and Repair, p. 109. [4] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, pp. 216-218. [5] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, pp. 218-219.

Question 329: Chediak-Higashi syndrome is characterized by which of the following defects?

A. Defects in phagolysosome function (Correct Answer)
B. Defects in macrophage production
C. Defects in leukocyte adhesion
D. Defects in microbicidal activity

Explanation: **Explanation:** **Chediak-Higashi Syndrome (CHS)** is an autosomal recessive disorder caused by a mutation in the **LYST (Lysosomal Trafficking Regulator) gene**. This mutation leads to a defect in protein trafficking, resulting in the failure of phagosomes to fuse with lysosomes [1]. 1. **Why Option A is Correct:** The hallmark of CHS is the formation of **giant lysosomal granules** in neutrophils and other cells [1]. Because of the LYST gene mutation, lysosomes cannot properly fuse with phagosomes to form **phagolysosomes** [1]. This prevents the effective digestion of engulfed bacteria, leading to recurrent pyogenic infections. 2. **Why Incorrect Options are Wrong:** * **Option B:** Macrophage production is generally normal; the defect lies in their intracellular function. * **Option C:** Leukocyte adhesion defects (LAD) are caused by deficiencies in integrins (CD18) or ligands, preventing leukocytes from migrating out of blood vessels. * **Option D:** While microbicidal activity is ultimately impaired, this is a broad term. Specifically, CHS is a defect of **degranulation/fusion**, whereas Chronic Granulomatous Disease (CGD) is the classic example of a primary defect in microbicidal activity (NADPH oxidase deficiency) [1]. **High-Yield Clinical Pearls for NEET-PG:** * **Peripheral Smear:** Pathognomonic **giant azurophilic granules** in neutrophils [1]. * **Clinical Tetrad:** 1. Recurrent pyogenic infections (Staph and Strep) [1]. 2. **Partial Oculocutaneous Albinism** (melanocytes cannot distribute melanin) [1]. 3. Progressive Neuropathy [1]. 4. Bleeding tendencies (due to defective dense granules in platelets) [1]. * **Associated Finding:** Neutropenia and Natural Killer (NK) cell deficiency [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, pp. 245-246.

Question 330: Chediak-Higashi syndrome is characterized by which of the following defects?

A. Defects in phagolysosome function (Correct Answer)
B. Defects in macrophage production
C. Defects in leukocyte adhesion
D. Defects in microbicidal activity

Explanation: **Explanation:** **Chediak-Higashi Syndrome (CHS)** is an autosomal recessive disorder caused by a mutation in the **LYST (Lysosomal Trafficking Regulator) gene**. This mutation leads to a defect in protein trafficking, resulting in the failure of phagosomes to fuse with lysosomes [1]. 1. **Why Option A is Correct:** The hallmark of CHS is the formation of **giant lysosomal granules** in neutrophils and other cells [1]. Because of the LYST gene mutation, lysosomes cannot properly fuse with phagosomes to form **phagolysosomes**. This impairs the intracellular killing of ingested bacteria, leading to recurrent pyogenic infections [1]. 2. **Why Incorrect Options are Wrong:** * **Option B:** Macrophage production is generally normal; the defect lies in the functional maturation of their organelles. * **Option C:** Leukocyte adhesion defects (LAD) are distinct disorders (e.g., LAD-1 due to CD18 deficiency) where neutrophils cannot migrate from the blood into tissues. * **Option D:** While microbicidal activity is ultimately reduced, this is a *consequence* of the primary defect in phagolysosome formation [1]. "Defects in microbicidal activity" is more classically associated with **Chronic Granulomatous Disease (CGD)**, where the NADPH oxidase system is defective. **High-Yield Clinical Pearls for NEET-PG:** * **Morphology:** Look for **Giant Azurophilic granules** in the cytoplasm of neutrophils on a peripheral smear [1]. * **Clinical Tetrad:** 1. **Partial Oculocutaneous Albinism** (due to abnormal melanocyte melanosomes) [1]. 2. **Recurrent Pyogenic Infections** (Staph and Strep) [1]. 3. **Progressive Neuropathy** [1]. 4. **Bleeding Tendencies** (due to dense body defects in platelets) [1]. * **Associated Finding:** Neutropenia and Natural Killer (NK) cell deficiency [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, pp. 245-246.

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Cells and Tissues of the Immune System

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