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Functions of White Blood Cell (WBC) Components

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1. Neutrophils (50-70% of WBCs)

Origin & Lifespan

• Bone marrow derived; released into blood with a very short intravascular half-life (~6-8 hours)
• Programmed to undergo constitutive apoptosis - a key mechanism to limit and resolve inflammation

Core Functions

• Recruited to sites of infection via chemokines and complement products (C5a, C3a)
• Marginate along endothelium, then undergo diapedesis (extravasation) into tissues

• Engulf and internalize pathogens coated with opsonins (IgG via Fc-γ receptors; C3b via CR1, CR3)
• Form phagolysosomes where killing occurs

• Oxidative (respiratory) burst: generates superoxide anion, hydrogen peroxide, and hypochlorous acid via NADPH oxidase
• Degranulation: releases myeloperoxidase (MPO), elastase, defensins, lactoferrin, and lysozyme from primary and secondary granules
• Neutrophil Extracellular Traps (NETs): chromatin-based traps that immobilize and kill extracellular bacteria

• Apoptotic neutrophils are phagocytosed by macrophages (efferocytosis) - this is the preferred mechanism to clear neutrophils from inflammatory foci and actively downregulates inflammatory signaling of neighboring cells
• Express death receptors (Fas/FasL, TNFR1) that regulate their own lifespan

• Mulholland and Greenfield's Surgery, p. 299-300; Medical Microbiology 9e

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2. Eosinophils (1-4% of WBCs)

Origin & Lifespan

• Bone marrow derived; after exiting marrow, they have a few hours intravascular half-life, then migrate to mucosa of lung, GI tract, and genitourinary tract
• Survival prolonged by IL-3, GM-CSF, and IL-5 (which inhibit apoptosis)

Core Functions

• Primary effectors against helminthic (parasitic worm) infections
• Release toxic granule proteins: Major Basic Protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase
• Generate superoxide and hydrogen peroxide (though less efficiently than neutrophils)

• Work alongside basophils and mast cells as key effectors in allergen-driven inflammation
• Express IgE receptors; stimulate histamine release from basophils and mast cells via MBP
• Recruited to sites by IL-5, PAF, LTB4, and CC chemokines (MIP-1α, RANTES, MCP-3) - especially in TH2-driven responses

• Release enzymes that inactivate histamine and slow-reacting substance of anaphylaxis (SRS-a), thereby also regulating basophil and mast cell function and tempering the allergic response
• Mulholland and Greenfield's Surgery, p. 322-323

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3. Basophils (<1% of WBCs)

Core Functions

• Bear high-affinity IgE receptors (FcεRI) on their surface
• Cross-linking of surface-bound IgE by allergen triggers degranulation: releases preformed histamine, heparin, and proteases
• Synthesize and release lipid mediators: leukotrienes (LTC4, LTD4 = SRS-a), prostaglandins, and PAF
• These mediators cause bronchoconstriction, vasodilation, and increased vascular permeability - the hallmarks of type I hypersensitivity

• Like eosinophils, contribute to defense against helminthic parasites under TH2 conditions

• Produce IL-4 and IL-13 which drive IgE class switching in B cells and maintain TH2 responses
• Cellular and Molecular Immunology; Murray & Nadel's Textbook of Respiratory Medicine

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4. Monocytes / Macrophages (3-8% of WBCs)

Tissue Macrophage Variants

Core Functions

• Engulf and degrade debris, apoptotic cells, microbes, and foreign material
• Unlike neutrophils, macrophages have mitochondria (enabling sustained metabolic activity) and lysosomes

• Express class II MHC molecules, enabling them to present processed antigen to CD4+ helper T cells and expand adaptive immune responses

• M1 macrophages (activated by IFN-γ from TH1 cells): produce IL-1, IL-6, TNF-α, IL-12, IL-23 - promoting inflammation, fever, and antimicrobial killing
• M2 macrophages (tissue-resident, yolk-sac derived): produce anti-inflammatory cytokines; involved in tissue maintenance, angiogenesis, and repair
• IL-1, IL-6, and TNF-α trigger acute-phase responses in the liver

• Fc-γ receptors (RI, RII, RIII) for IgG
• CR1, CR3 for complement C3b products
• Toll-like receptors (TLRs) and other PRRs recognizing PAMPs (pathogen-associated molecular patterns)
• Medical Microbiology 9e, p. 63-64

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5. Lymphocytes (20-40% of WBCs)

T Lymphocytes

• PD-1: co-inhibitory receptor; maintains tolerance but leads to T-cell exhaustion in chronic infection/cancer. Blocking PD-1 (e.g., pembrolizumab) restores T-cell function
• TIM-3: limits T-cell response duration; upregulated in cancer TILs, correlates with exhaustion
• LAG-3: negative regulator of T-cell homeostasis; expressed on activated CD4+, CD8+, and NK cells

B Lymphocytes

• Mature in bone marrow; identified by surface immunoglobulins, class II MHC, CR1, CR2
• Primary function: produce antibodies (humoral immunity)
• Internalize antigen, process it, and present it to T cells to request T-cell help
• After activation, differentiate into:
  • Plasma cells: antibody factories with abundant cytoplasm, small nuclei
  • Memory B cells: long-lived, express CD45RO; re-activated rapidly on re-exposure to antigen
• B-1 cells (fetal liver origin): continuously produce low-affinity antibodies against bacterial polysaccharides, ABO blood group antigens, and self-antigens
• Marginal zone B cells (spleen): rapid T-independent antibody responses to encapsulated bacteria (e.g., Streptococcus pneumoniae)

Natural Killer (NK) Cells / ILC1s

• Large granular lymphocytes; part of the Innate Lymphoid Cell (ILC) family
• Do not require prior sensitization or MHC restriction (unlike CTLs)
• Kill virally infected and tumor cells whose MHC class I expression is downregulated (missing-self recognition)
• Cytoplasmic granules contain perforin and granzymes for cytolytic killing
• Capable of ADCC (antibody-dependent cellular cytotoxicity): kill antibody-coated target cells via Fc receptor
• Produce IFN-γ, activating macrophages and bridging innate and adaptive immunity
• Medical Microbiology 9e, p. 63-65; Mulholland and Greenfield's Surgery, p. 322-323

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Summary Table