Mechanisms of Macrophages – Quiz
Source Text (for your reference)
Definition:
Macrophages are tissue cells derived from:
1. BONE MARROW → HEMATOPOIETIC STEM CELL
2. YOLK SAC
3. FETAL LIVER (developmental stages)
The half-life of blood monocytes is about 1 day; tissue macrophages is several months or years.
Specific locations and types:
Circulation – Monocytes
Liver – Kupffer cells
Spleen, Lymph nodes – Sinus histiocytes
CNS – Microglia
Lungs – Alveolar macrophages
Skin – Langerhans cells/dendritic cells
Functions of macrophages:
1. Ingest and eliminate microbes and dead tissues (phagocytosis).
2. Initiate tissue repair.
3. Secrete mediators of inflammation.
4. Macrophage-lymphocyte interactions.
Activation pathways:
Classic activation: IFN-γ, TLR agonists, MHC, CD80/86, APCs, iNOS, ROS, proteolytic enzymes, phagosome maturation.
Alternative activation: Th2, IL-4, IL-13, increased endocytosis, increased MHC class II, arginase vs iNOS, reduced killing of intracellular pathogens, healing, fibrogenic cytokines, angiogenesis, collagen remodeling.
Phagocytosis: recognition and attachment, engulfment (phagocytic vacuole), killing/degradation.
Recognition/attachment via PAMs, PRRs (e.g., TLR), and opsonins (IgG, C3b). Opsonins recognized by FcγRs and CR3. Bruton’s disease (XLA): defective B cell maturation → absence of Ig → defective opsonization.
Receptors: Fc receptors, complement receptors (CR1, CR3, CR4), mannose receptors, scavenger receptors.
FcR-mediated phagocytosis: clustering, ITAM phosphorylation (SRC kinase), SYK activation, engulfment.
Complement receptor-mediated phagocytosis: CR1, CR3, CR4, induced by PKC activators (PMA, TNF-α, GM-CSF). IgG-opsonized particles use pseudopodia; complement-coated particles sink into cell. FcR → ROS, pro-inflammatory molecules.
Mannose receptor-mediated phagocytosis: MR binds mannose/fucose, expressed on macrophages, pro-inflammatory (IL-1β, IL-6, GM-CSF, TNF-α, IL-12).
Scavenger receptors: bind microbes and modified LDL; Kupffer cells rich in these; role in atherosclerosis (foam cells).
Phagolysosome and maturation: particle internalization and phagosome maturation. Early phagosome: mildly acidic (pH 6.1–6.5), poor hydrolytic activity, refractory to lysosome fusion. Late phagosome: more acidic (pH 5.5–6.0), proteases, LAMPs. Phagolysosome: even more acidic.
Microbicidal activity: acidification (V-ATPases), ROS and NO, lysosomal enzymes and antimicrobial peptides. Respiratory burst: rapid release of ROS (superoxide, hydrogen peroxide).
ROS: O2 → ROS, H2O2 → OCl− (via myeloperoxidase). H2O2–MPO–halide system is highly bactericidal. MPO deficiency (hereditary or acquired) → increased susceptibility to infection.
Role in tuberculosis: TH1 response after ~3 weeks; IL-12 drives TH1 differentiation; tuberculin positivity. TH1 → IFN-γ → macrophage activation, TNF release → monocyte recruitment; TNF antagonists (e.g., in RA) increase risk of TB reactivation. M. tuberculosis can arrest phagosome maturation.
Leukocyte-mediated tissue injury: collateral damage in normal defense; autoimmune diseases; excessive responses such as allergy/asthma.
Macrophage–lymphocyte interaction: reciprocal activation and regulation.
