The reticuloendothelial system (RES), now largely termed the mononuclear phagocyte system (MPS), comprises macrophages and related phagocytic cells in organs such as liver (Kupffer cells), spleen, lymph nodes and bone marrow. For B. Pharm students, understanding RES structure, cellular markers (CD68), phagocytosis mechanisms, opsonization, antigen presentation, cytokine-mediated activation (IFN-γ, M-CSF), and pharmacological implications like nanoparticle and liposomal drug clearance is essential for rational drug design and immunopharmacology. This topic links immunology with pharmacokinetics, clinical pathology and drug delivery strategies. You will be tested on receptors (Fc, complement, scavenger), intracellular killing pathways (NADPH oxidase, phagolysosome), clinical conditions (splenectomy, hemophagocytic syndromes) and drug delivery challenges related to RES uptake. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. What alternative term is commonly used instead of the historical name “reticuloendothelial system”?
- Complement system
- Neutrophil network
- Mononuclear phagocyte system (MPS)
- Adaptive immune system
Correct Answer: Mononuclear phagocyte system (MPS)
Q2. Which cell type forms the core functional unit of the RES/MPS?
- B lymphocytes
- Macrophages (e.g., Kupffer, splenic, alveolar)
- Endothelial cells
- Platelets
Correct Answer: Macrophages (e.g., Kupffer, splenic, alveolar)
Q3. Kupffer cells, key RES components, are located primarily in which anatomical site?
- Bile canaliculi
- Hepatic sinusoids (sinusoidal lining)
- Portal triad
- Centrilobular vein
Correct Answer: Hepatic sinusoids (sinusoidal lining)
Q4. A major physiological function of the RES is:
- Secretion of digestive enzymes
- Phagocytosis and clearance of pathogens, senescent cells and particles
- Production of red blood cells
- Hormone synthesis
Correct Answer: Phagocytosis and clearance of pathogens, senescent cells and particles
Q5. Which immunohistochemical marker is most commonly used to identify tissue macrophages in histology?
- CD3
- CD20
- CD68
- CD31
Correct Answer: CD68
Q6. Which molecule is recognized classically by Fc receptors on macrophages to promote opsonic phagocytosis?
- C3a
- IgM
- IgG
- Albumin
Correct Answer: IgG
Q7. The enzyme complex responsible for the respiratory (oxidative) burst in phagocytes is:
- Myeloperoxidase only
- NADPH oxidase complex
- Cyclooxygenase
- DNA polymerase
Correct Answer: NADPH oxidase complex
Q8. Fusion of a phagosome with a lysosome yields which compartment for microbial killing?
- Autophagosome
- Phagolysosome
- Endoplasmic reticulum
- Golgi vesicle
Correct Answer: Phagolysosome
Q9. Chronic granulomatous disease (CGD) is primarily due to a defect in which pathway related to RES function?
- Antigen presentation via MHC II
- NADPH oxidase–mediated respiratory burst
- Lysosomal acid hydrolases
- Fc receptor expression
Correct Answer: NADPH oxidase–mediated respiratory burst
Q10. How do macrophages primarily present processed antigens to CD4+ T lymphocytes?
- On MHC class I molecules
- Secreted peptide fragments
- On MHC class II molecules
- Via toll-like receptors
Correct Answer: On MHC class II molecules
Q11. Tissue macrophages are derived from which circulating precursor?
- Neutrophils
- Eosinophils
- Monocytes
- Lymphocytes
Correct Answer: Monocytes
Q12. Which receptor family on macrophages recognizes oxidized low-density lipoprotein and apoptotic cells?
- T cell receptor
- Scavenger receptors
- B cell receptor
- Insulin receptor
Correct Answer: Scavenger receptors
Q13. A common pharmacological consequence of RES uptake of liposomal drugs is:
- Prolonged systemic half-life in all cases
- Rapid clearance into liver and spleen, reducing circulation time
- Complete renal elimination
- Enhanced blood–brain barrier penetration
Correct Answer: Rapid clearance into liver and spleen, reducing circulation time
Q14. Which surface modification is most effective to reduce RES recognition and prolong nanoparticle circulation?
- Cholesterol coating
- PEGylation (polyethylene glycol)
- Conjugation with albumin
- Increasing particle charge
Correct Answer: PEGylation (polyethylene glycol)
Q15. Which cytokine is a key activator of classical (M1) macrophage activation?
- IL-10
- IL-4
- Interferon-gamma (IFN-γ)
- Transforming growth factor-beta (TGF-β)
Correct Answer: Interferon-gamma (IFN-γ)
Q16. The M2 macrophage phenotype is most associated with which function?
- Pro-inflammatory microbicidal activity
- Tissue repair and anti-inflammatory responses
- Immediate hypersensitivity reactions
- Antibody production
Correct Answer: Tissue repair and anti-inflammatory responses
Q17. Which organ is the primary blood filter and a central RES site for removing opsonized particles?
- Kidney
- Spleen
- Thyroid
- Adrenal gland
Correct Answer: Spleen
Q18. In the spleen, which macrophage population is primarily involved in the phagocytosis of senescent red blood cells?
- Marginal zone B cells
- White pulp dendritic cells
- Red pulp macrophages
- Endothelial sinus cells
Correct Answer: Red pulp macrophages
Q19. Hemophagocytic lymphohistiocytosis (HLH) is characterized by excessive activation of which cells?
- Neutrophils causing tissue ischemia
- Macrophages (histiocytes) causing hemophagocytosis
- Erythrocytes producing cytokines
- B cells producing autoantibodies
Correct Answer: Macrophages (histiocytes) causing hemophagocytosis
Q20. Complement receptor CR1 (CD35) on phagocytes primarily binds which complement fragment?
- C5a
- C3b
- C4a
- C9
Correct Answer: C3b
Q21. The process by which macrophages remove aged erythrocytes is called:
- Autolysis
- Erythrophagocytosis
- Hemolysis by complement
- Apoptosis
Correct Answer: Erythrophagocytosis
Q22. Patients who have undergone splenectomy are at increased risk of severe infection by:
- Gram-negative anaerobes only
- Encapsulated bacteria such as Streptococcus pneumoniae
- Fungal molds exclusively
- Non-enveloped viruses
Correct Answer: Encapsulated bacteria such as Streptococcus pneumoniae
Q23. Which receptor on macrophages recognizes the Fc portion of IgG antibodies to mediate antibody-dependent phagocytosis?
- Fcε receptor
- Fcγ receptor (Fc gamma receptor)
- Complement receptor CR3 only
- Toll-like receptor 4
Correct Answer: Fcγ receptor (Fc gamma receptor)
Q24. A key role of RES macrophages in iron metabolism is to:
- Excrete iron into bile
- Store and recycle iron from senescent erythrocytes
- Synthesize transferrin in plasma
- Convert iron to hemoglobin
Correct Answer: Store and recycle iron from senescent erythrocytes
Q25. Which laboratory technique is most specific for identifying macrophages in tissue sections?
- Gram stain
- CD68 immunohistochemistry
- Periodic acid–Schiff (PAS) stain
- Prussian blue only
Correct Answer: CD68 immunohistochemistry
Q26. The predominant organs responsible for clearance of colloidal particles and many nanoparticles are:
- Lungs and brain
- Liver (Kupffer cells) and spleen
- Bone marrow exclusively
- Kidneys and urinary tract
Correct Answer: Liver (Kupffer cells) and spleen
Q27. Which co-stimulatory molecules expressed by activated macrophages are critical for naive T-cell activation?
- CD3 and CD28
- CD80/CD86 (B7 family)
- CD19 and CD21
- MHC class I only
Correct Answer: CD80/CD86 (B7 family)
Q28. The classical complement pathway, which enhances opsonization for RES clearance, is initiated by:
- Spontaneous hydrolysis of C3 only
- Antigen–antibody complexes (IgM or IgG)
- Lipopolysaccharide binding to mannose-binding lectin
- Direct C9 activation
Correct Answer: Antigen–antibody complexes (IgM or IgG)
Q29. Which class of enzymes within lysosomes is primarily responsible for degrading internalized microbes?
- Lysosomal acid hydrolases and proteases
- DNA topoisomerases
- RNA polymerases
- Fatty acid synthases
Correct Answer: Lysosomal acid hydrolases and proteases
Q30. Which growth factor is most important for the proliferation and differentiation of macrophage lineage cells?
- Erythropoietin (EPO)
- Granulocyte colony-stimulating factor (G-CSF)
- Macrophage colony-stimulating factor (M-CSF / CSF-1)
- Insulin-like growth factor 1 (IGF-1)
Correct Answer: Macrophage colony-stimulating factor (M-CSF / CSF-1)

I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
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