Expansion
Margination, rolling, adhesion, transmigration, chemotaxis, phagocytosis and killing
Expansion
- Margination: neutrophils move to the vessel periphery as flow slows
- Rolling: mediated by selectins, a weak transient interaction
- Firm adhesion: mediated by integrins binding ICAM on activated endothelium
- Transmigration (diapedesis) between endothelial cells
- Chemotaxis along gradients of C5a, interleukin-8, leukotriene B4 and bacterial peptides
- Phagocytosis, greatly enhanced by opsonisation with IgG and C3b
- Killing: oxygen-dependent by the respiratory burst (NADPH oxidase generating superoxide, then myeloperoxidase producing hypochlorite), and oxygen-independent by lysozyme, lactoferrin and defensins
Defects map onto the steps:
- Leucocyte adhesion deficiency: integrin defect, causing delayed umbilical cord separation and recurrent infection with no pus
- Chronic granulomatous disease: NADPH oxidase defect, so organisms are ingested but not killed; catalase-positive organisms are the problem. Diagnosed by the nitroblue tetrazolium or dihydrorhodamine test
- Chediak-Higashi: defective phagolysosome fusion