How do neutrophils (PMNs) get from the blood into tissue to kill infection?

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♥️Immunology

PMNs
1. Roll
2. Adhere
3. Transmigrate through endothelium into tissue

The above process depends on different types of adhesion molecules:
1. Selectins
2. Integrins
3. ICAMs
1. PMNs loosely attach to endothelium via selectins
2. PMN firmly adheres to endothelium via β2 integrin
3. PMNs transmigrates via LFA1-ICAM2 binding

CD18 = β2 chain common to all β2 integrins
Selectins/ICAMs modified by fucosylation
Leukocyte Adhesion Deficiency (LAD) =
Disorders of leukocyte rolling, adhesion and transmigration

PMNs made but can't get into tissue!
Delayed separation of umbilical cord
Recurrent bacterial infections in skin
Leukocytosis
No pus formation

3 types:
LAD-1
LAD-II
LAD-III
LAD-I:
ITGB2 gene=β2 integrin (CD18)

LAD-II
SLC35C1 gene=GDP-fucose transporter-1
Unable to fucosylate selectins on PMNs
Unfucosylated selectin can't bind endothelium

LAD-III
KINDLIN3
Bleed

Diagnosis by flow
LAD-1 = Absence of CD18, CD11a/b/c
LAD-II = Absence of CD15a (SLeX)
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