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USMLE Step 1ImmunologyEP 12 of 14

Leukocyte adhesion deficiency: CD18 and neutrophil extravasation

A newborn has a very high white cell count and an infection with no pus. Follow a neutrophil out of the blood to see which step fails in leukocyte adhesion deficiency type 1, and how type 2 differs.

  • 5:01 video
  • 3 min read
  • 7 sources
  • Published 15 Nov 2026
Video lesson · 5:01 · Watch on YouTubeSeries: Immunology · @medservatory
Chapters (9)
By the end of this lesson

Relate the steps of leukocyte extravasation to the defect in leukocyte adhesion deficiency type 1 (CD18) and its clinical clues.

The short version

  1. Neutrophils leave the blood in four steps: roll, activate, stick, cross.
  2. Leukocyte adhesion deficiency type 1 breaks the sticking step, because the shared beta chain CD18 (gene ITGB2) is missing or reduced.
  3. The classic picture is late umbilical cord separation, marked neutrophilia and infections of skin and mucosa with no pus.
  4. Leukocyte adhesion deficiency type 2 is a fucose problem: neutrophils cannot roll, CD18 is normal, and the Bombay blood group appears.
  5. Diagnosis is by flow cytometry for CD18 and CD11; a stem-cell transplant can cure severe disease.

Leukocyte adhesion deficiency: a high white count and no pus

A newborn's umbilical stump will not fall off. The stump becomes infected and his white cell count is enormous. Yet the infected skin makes no pus.

How can a high white count give no pus? The answer is leukocyte adhesion deficiency, and to see it you have to follow a neutrophil out of the blood. To make pus, neutrophils must leave the blood and enter the tissue.[1][2]

How neutrophil extravasation works: roll, activate, stick, cross

Leukocyte extravasation is the route a neutrophil takes from the vessel into infected tissue. The lesson treats it as four steps.[1][2]

  1. RollingSelectins on the inflamed endothelium catch the neutrophil, so it rolls along the vessel wall.
  2. ActivationChemokines switch on the neutrophil's integrins.
  3. Firm adhesionThe integrin LFA-1 binds ICAM-1 on the endothelium, and the neutrophil stops.
  4. TransmigrationThe neutrophil squeezes between endothelial cells and follows the chemical trail to the infection.

The memory line is: roll, activate, stick, cross.[1][2]

Leukocyte adhesion deficiency type 1: the CD18 defect

Leukocyte adhesion deficiency type 1 (LAD type 1) breaks step three, firm adhesion. The gene ITGB2 encodes CD18, the shared beta chain of the beta-2 integrins.[2]

The beta-2 integrins named in the lesson
IntegrinMade ofShared chain
LFA-1CD11a + CD18CD18
Mac-1CD11b + CD18CD18

The disease is autosomal recessive, so girls are affected too.[2]

The neutrophil can still roll on selectins, but without CD18 it cannot stick or cross.[2][5] Other integrins such as VLA-4 cannot rescue it, because neutrophils barely express them.[2]

Why the white count climbs: neutrophilia, late cord, no pus

Neutrophils cannot leave the blood normally, so they build up in it and the count climbs.[2][3]

  • A marked neutrophilia.
  • Infections of the skin and mucosa that form no pus.
  • Late separation of the umbilical cord.
  • In milder cases, survival to adulthood with periodontitis.

Severe disease often has under 2 percent of the normal CD18 on neutrophils.[2][4]

Diagnosis and treatment

The diagnosis is flow cytometry for CD18 and CD11.[3][4]

A stem-cell transplant can cure it.[2][4]

Leukocyte adhesion deficiency type 2: the contrast

Type 2 has a different fault: the Golgi fucose transporter, encoded by SLC35C1. Without fucosylated selectin ligands, neutrophils cannot even roll, though CD18 is normal.[2][6]

Add severe growth retardation and the Bombay blood group.[2][6]

Type 1 compared with type 2
FeatureType 1Type 2
FaultCD18 (ITGB2)Golgi fucose transporter (SLC35C1)
Step that failsFirm adhesion and crossingRolling
CD18MissingNormal
Extra cluesLate cord, high count, no pusSevere growth retardation, Bombay blood group

Worked example: where does the neutrophil stop?

Sort the defect by the step that fails
  1. Cannot roll: type 2.
  2. Rolls but cannot stick: type 1, with a high count and no pus.
  3. Late cord, huge neutrophil count and pus-free infection: type 1.

Practice question

Original · USMLE style
Your turnQB-MS-S1-IMM-008-01

A 5-week-old girl has fever and redness around an umbilical stump that has not yet separated. The area is swollen but there is no pus. Her leukocyte count is 32,000/mm3, with 85% neutrophils. Immunoglobulin levels and T-cell counts are normal. Flow cytometry shows markedly decreased CD11a, CD11b and CD18 on neutrophils.

Which of the following best explains her infections?
Pick one option. Your answers stay on this device.

Common questions

What is leukocyte adhesion deficiency type 1?

It is an autosomal recessive disorder in which the CD18 beta chain, encoded by ITGB2, is missing or reduced. Neutrophils cannot stick firmly to the vessel wall or cross it.

Why is there no pus in leukocyte adhesion deficiency?

Neutrophils must leave the blood and enter the tissue to make pus. Without CD18 they stay in the blood, so infections form no pus and the neutrophil count climbs.

How is leukocyte adhesion deficiency diagnosed?

By flow cytometry for CD18 and CD11. Severe disease often has under 2 percent of the normal CD18 on neutrophils.

What is the difference between LAD type 1 and type 2?

In type 1 neutrophils can roll but cannot stick, because CD18 is missing. In type 2 the Golgi fucose transporter (SLC35C1) is faulty, neutrophils cannot roll, CD18 is normal, and the Bombay blood group appears.

Can leukocyte adhesion deficiency be cured?

A stem-cell transplant can cure it.

Transcript

Read the full narration, by chapter598 words

0:00The case: a high white count and no pus

A newborn's umbilical stump will not fall off. The stump becomes infected, and his white cell count is enormous. Yet the infected skin makes no pus. How can a high white count give no pus? Today: follow a neutrophil out of the blood, and see which step fails in leukocyte adhesion deficiency type 1.

0:21Follow a neutrophil: roll, activate, stick, cross

To make pus, neutrophils must leave the blood and enter the tissue. Step one, rolling: selectins on the inflamed endothelium catch the neutrophil, so it rolls along the vessel wall. Step two, activation: chemokines switch on the neutrophil's integrins. Step three, firm adhesion: the integrin LFA-1 binds ICAM-1 on the endothelium, and the neutrophil stops. Step four, transmigration: it squeezes between endothelial cells and follows the chemical trail to the infection. Roll, activate, stick, cross.

1:01LAD type 1: ITGB2, CD18, LFA-1 and Mac-1

Leukocyte adhesion deficiency type 1 breaks step three. The gene ITGB2 encodes CD18, the shared beta chain of the beta-2 integrins. LFA-1 is CD11a with CD18, and Mac-1 is CD11b with CD18. The disease is autosomal recessive, so girls are affected too. The neutrophil can still roll on selectins, but without CD18 it cannot stick or cross. Other integrins such as VLA four cannot rescue it, because neutrophils barely express them.

1:38The count climbs: neutrophilia, late cord, no pus

So neutrophils stay in the blood, and the count climbs. The classic picture is a marked neutrophilia with infections of the skin and mucosa that form no pus. The umbilical cord separates late. Severe disease often has under 2% of the normal CD18 on neutrophils. Milder cases can reach adulthood, with periodontitis. The diagnosis is flow cytometry for CD18 and CD11. A stem-cell transplant can cure it.

2:09LAD type 2: fucose and selectin ligands

Compare type 2. Its fault is the Golgi fucose transporter, SLC35C1. Without fucosylated selectin ligands, neutrophils cannot even roll, though CD18 is normal. Add severe growth retardation and the Bombay blood group.

2:28Worked example: where does the neutrophil stop?

Worked example: ask where the neutrophil stops. It cannot roll: type 2. It rolls but cannot stick: type 1, with a high count and no pus. Our newborn has a late cord, a huge neutrophil count and pus-free infection. That is type 1.

2:47Your turn: a practice question

Your turn. A five-week-old girl has fever and redness around an umbilical stump that has not yet separated. The area is swollen but there is no pus. Her leukocyte count is 32,000 per mm³, 85% neutrophils. Immunoglobulins and T-cell counts are normal. Flow cytometry shows markedly decreased CD11a, CD11b and CD18 on neutrophils. Which of the following best explains her infections? A, neutrophils cannot roll along activated endothelium. B, neutrophils cannot adhere firmly to activated endothelium. C, neutrophils cannot generate superoxide in the phagosome. D, neutrophils cannot sense chemokines released at the infection. E, neutrophils cannot leave the bone marrow. Pause here and decide.

3:48The answer, one option at a time

A is out: rolling needs selectins and their fucosylated ligands, which are intact here; failure to roll is type 2. C is out: failed superoxide production gives catalase-positive abscesses, not pus-free infection with a high neutrophil count. D is out: chemokines act upstream and are sensed; the integrin they would activate is the part that is missing. E is out: her count is high, so release from the marrow is fine, and the cells simply stay in the blood. So the answer is B. Without CD18, LFA-1 and Mac-1 cannot bind, so neutrophils cannot stick to the vessel wall or cross it, and no pus forms.

4:33Recap pocket card

Three things to keep. One: roll, activate, stick, cross; type 1 fails at sticking, because CD18 is missing. Two: late cord separation, marked neutrophilia and pus-free infection. Three: type 2 cannot roll, and comes with the Bombay blood group. Next, transplant rejection: hyperacute, acute and chronic.

Sources

Numbers in the text, e.g. [1], point here
  1. Europe PMC (PMC5195840). Neutrophil extravasation cascade. europepmc.org/article/PMC/PMC5195840
  2. Europe PMC (PMC8998723). LFA-1 and leukocyte adhesion deficiency type I. europepmc.org/article/PMC/PMC8998723
  3. Europe PMC (PMC10619948). Leukocyte adhesion deficiency case report, Sao Paulo Med J. europepmc.org/article/PMC/PMC10619948
  4. Europe PMC (PMC13091988). International clinical consensus on LAD-I (modified Delphi). europepmc.org/article/PMC/PMC13091988
  5. Europe PMC (PMC7930317). Beta-2 integrin signalling in neutrophils. europepmc.org/article/PMC/PMC7930317
  6. Europe PMC (PMC12815614). Congenital disorders of glycosylation due to defective membrane transporters (SLC35C1-CDG). europepmc.org/article/PMC/PMC12815614
  7. Chronic granulomatous disease, for the contrast option: europepmc.org/article/PMC/PMC11239527 · europepmc.org/article/PMC/PMC5709447

The practice question is original and its patient is synthetic. Every fact is checked against the sources above in independent accuracy reviews. Always follow your local guidelines and your own laboratory’s ranges.

Image credits. Illustrations: Servier Medical Art (smart.servier.com), CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/), adapted (recoloured, outlined, resized): neutrophil, endothelial cell. NIAID NIH BioArt (public domain): Staphylococcus aureus, bone marrow. Icons: Health Icons (CC0): baby, tooth. The vessel wall, cascade, LFA-1 and Mac-1 heterodimers, charts, pedigree, cards and all handwriting are drawn in code (original). No AI-generated teaching images.

Corrections. None so far. Spotted an error? Email info@medservatory.com with the lesson code MS-S1-IMM-008.

For exam study only, not medical advice. Read the medical disclaimer.

In this series

Playlist on YouTube
← Previous · EP 11Chronic granulomatous disease: NADPH oxidase and the respiratory burst
  1. EP 01MHC I vs MHC II: how antigen presentation works5:03
  2. EP 02T-cell activation: the two-signal model4:58
  3. EP 03Th1, Th2, Th17 and Treg: helper T-cell subsets5:13
  4. EP 04Antibody isotypes and class switching5:13
  5. EP 05Central vs peripheral tolerance: how lymphocytes learn self-tolerance5:26
  6. EP 06Complement system explained: three pathways, one ending5:24
  7. EP 07Complement deficiencies: C1q, C3, C5–C9 and C1 inhibitor5:15
  8. EP 08Hypersensitivity types I to IV: the four effectors5:20
  9. EP 09B-cell vs T-cell immunodeficiency: predict the infections5:24
  10. EP 10Hyper IgM syndrome: CD40 ligand and class switching5:19
  11. EP 11Chronic granulomatous disease: NADPH oxidase and the respiratory burst5:20
  12. EP 12Leukocyte adhesion deficiency: CD18 and neutrophil extravasation5:01
  13. EP 13Transplant rejection explained: hyperacute, acute, chronic and GVHD5:51
  14. EP 14Vaccine types explained: live, inactivated, conjugate and mRNA5:41