Question

Individuals with inactivating mutations in the integrin CD18 have elevated levels of leukocytes (leukocytosis) and neutrophils (neutrophilia) in the bloodstream, but they have recurrent problems fighting pyogenic bacterial infections. Explain in 4-5 sentences why individuals with CD18 mutations have problems defending against bacterial infection and why these mutations cause leukocytosis.

Answer 1

ANSWER:- Before knowing why mutation in CD18 cause problems facing bacterial infection, it is necessary to understand the process of extravasation. Normally in bloodstream phagocytes (mostly neutrophils which is a leukocyte) are present waiting for signals in the form of cytokines to come if there is any kind of infection or stress in body. Once the cytokines arrive in bloodstream, the phagocytes rush to the infection site by the process called Extravasation. Extravasation has following steps:-

1. Phagocyte attaches to selectin on endothelial cell of vessel wall to roll on the vessel wall.

2. Then phagocyte via surface molecules integrins like CD18 , adheres to cellular adhesion molecules on endothelial cells.

3. Phagocytes adhered to endothelial cells then transmigrate through endothelial cells junction into extravascular tissue and reach to infection site where they engulf bacteria or fungi, and forming pus.

• Now what happens in a person suffering from CD18 mutation, the second step of extravasation that is adherence ointophagocyte via integrin subunit CD18 to endothelial cell doesnt take place, hence the transmigration of phagocytes doesn't take place and bacteria is not eaten up by phagocytes resulting in accumulation of bacteria and trouble fighting the infection.

(Know that phagocyte is neutrophils i.e; leucocyte)

Cause of leucocytosis:-

As the phagocytes (that is neutrophils which are leukocytes) can't adhere to endothelial cell wall and transmigrate into extra vascular tissue hence the leucocytes will accumulate in bloodstream causing leucocytosis.