Leukocyte adhesion deficiency

Elements of the case

• female patient who got a bacterial infection at 4 weeks of age. this is really early, and the mom’s antibodies should definitely still be around to help the baby. this makes us think that whatever the antibodies are recruiting is not actually working

• positive family history in a brother

• very high neutrophil count, even uninfected. normal is 5000-10000; here we are talking 50000

• normal thymus, spleen by X-ray

• normal Ig levels

• white cells did not migrate normally when tested

• no LFA 1

Principles to understand

• function of adhesion molecules in normal migration of WBC

• when you turn on adaptive immune response, T cells and APCs have to bind, adhere, and costimulate in order for the T cell to be turned on appropriately

Neutrophil

• multilobed nucleus

• granules

Neutrophil diapedesis

• red cells roar right down the middle of the capillary

• white cells actually have adhesion molecules that help them stick to the endothelium, so they roll along the endothelium

• at any given time, ½ of the neutrophils in our bodies are marginated (i.e., stuck on endothelial cells) so the neutrophil count we get from the lab, the free neutrophil count, is actually about half of the actual number of neutrophils that our body contains

• if you go running, sympathetic stimulation and peripheral vasodilation will cause you to demarginate your neutrophils. a blood test will reflect that your free neutrophils have increased in number although the total number of neutrophils in your body is probably not drastically different. these freely-rolling neutrophils can now choose to marginate more specifically at the site of any inflammation

• there are many adhesion molecules involved, including sialyl-Lewis^x. normally, neutrophils roll and attach to the endothelium loosely

• when chemokines are near the endothelium, neutrophils adhere more strongly and actually stick to the endothelium. this is mediated by LFA-1 on neutrophil and ICAM-I on endothelial cell. ultimately, the neutrophil moves out of the bloodstream

Category: Pathology Notes