STEPTRACKERGENERAL PRINCIPLES | PATHOLOGY + IMMUNOLOGY | HIGH-YIELD REVIEW

Neutrophil Arrival & Killing

From the bloodstream to the microbe in seven steps — each step has a molecule, and each molecule has a disease.

FOCUS ON
Learn the ladder: margination → rolling (selectins) → adhesion (integrins) → transmigration → chemotaxis → phagocytosis → killing. Questions place a defect or a drug on one rung.
STEP
WHAT HAPPENS
KEY MOLECULES
DEFECT / CLINICAL LINK
1 · Margination
slow flow
Vasodilation slows blood; neutrophils drift to the vessel wall.
Driven by vasodilators (histamine, PGs)
Steroids, epinephrine → demargination → neutrophilia
2 · Rolling
weak, reversible
Selectins on endothelium catch sialyl Lewis X on the neutrophil.
P-selectin (Weibel-Palade bodies, released by histamine) · E-selectin (induced by TNF, IL-1)
LAD type 2: no sialyl Lewis X (fucosylation defect)
3 · Tight adhesion
firm stop
Neutrophil integrins switch to high affinity and grip endothelial ligands.
Integrins LFA-1, Mac-1 (CD11/CD18) ↔ ICAM-1, VCAM-1 · activated by C5a, LTB₄
LAD type 1: CD18 defect → delayed cord separation, no pus
4 · Transmigration
diapedesis
Neutrophils squeeze between endothelial cells of postcapillary venules.
PECAM-1 (CD31)
Site: postcapillary venules
5 · Chemotaxis
follow the gradient
Neutrophils crawl toward the highest concentration of attractant.
C5a, LTB₄, IL-8, kallikrein, bacterial products
Chédiak-Higashi: impaired migration
6 · Phagocytosis
engulf
Opsonized microbe is engulfed; phagosome fuses with lysosome → phagolysosome.
Opsonins: IgG (Fc receptor) and C3b
Chédiak-Higashi: LYST defect → fusion fails, giant granules
7a · O₂-dependent killing
respiratory burst
NADPH oxidase → O₂•⁻ → (SOD) H₂O₂ → (MPO + Cl⁻) HOCl.
NADPH oxidase, superoxide dismutase, myeloperoxidase
CGD (no NADPH oxidase) · MPO deficiency (Candida)
7b · O₂-independent killing
granule proteins
Enzymes and peptides in granules kill without O₂.
Lysozyme, defensins, lactoferrin, major basic protein (eosinophils)
Backup killing in anaerobic sites
8 · Resolution
clean-up
Neutrophils undergo apoptosis; macrophages arrive (2–3 days) and clear debris.
Lipoxins, IL-10, TGF-β
Failure to resolve → chronic inflammation or abscess

Mechanism — the recruitment ladder

MarginationSlow flow
→
RollingSelectins
→
AdhesionIntegrins (CD18)
→
DiapedesisPECAM-1
→
ChemotaxisC5a, LTB₄, IL-8
→
KillPhagolysosome + burst

Neutrophils dominate the first ~24 hours; macrophages take over by 48–72 hours.

Who switches on what

SIGNAL
ACTS ON
EFFECT
Histamine
Endothelium
P-selectin released from Weibel-Palade bodies
TNF, IL-1
Endothelium
E-selectin, ICAM-1, VCAM-1 expressed
C5a, LTB₄
Neutrophil
Integrins to high-affinity state
Glucocorticoids
Both
↓ adhesion → demargination → ↑ blood neutrophils; ↓ eosinophils, lymphocytes
MPO pigment
Pus
Blue-green heme enzyme gives pus its green tint

How it's tested

COMMON CONFUSIONSelectins mediate rolling and integrins mediate firm adhesion. LAD1 is the integrin (CD18) defect; LAD2 is the selectin-ligand defect.
THE TRAPA patient on prednisone has WBC 14,000 with neutrophilia and no infection. This is demargination, not infection or leukemia.
YOUR APPROACHFind which rung failed. No pus despite high blood neutrophils means the cells can't leave vessels (adhesion). Pus with organisms surviving inside means a killing defect.

If you see… think…

Umbilical cord still attached at 5 weeks, no pus, WBC very high → LAD type 1 (CD18)
Neutrophilia days after starting steroids → demargination
Rolling depends on → selectins binding sialyl Lewis X
Histamine-triggered P-selectin release → Weibel-Palade bodies
Firm arrest requires → integrins (LFA-1/Mac-1) on ICAM-1
Green pus → myeloperoxidase
Catalase-positive infections, abnormal DHR test → CGD
Albinism, giant granules, neuropathy → Chédiak-Higashi
Opsonins that speed phagocytosis → IgG and C3b