Lecture 2 - Neutrophils

How do neutrophils exit the circulation?

They exit through diapedesis

What is diapedesis?

Passage of cells through intact vessel walls and regulated by integrins and selectins

What is the main function of neutrophils?

Seeking and destroying foreign material and microorganisms

How can neutrophils seek?

Through chemotaxis, motility, and diapedesis

How can neutrophils destroy?

Through phagocytosis and digestion

What is chemotaxis?

Directed movement of phagocytic cells to a site of injury via concentration gradient (chemoattractant). They pick up a low concentration then follows it until a high concentration is found

What is locomotion?

Random and non-directional movement usually in the marginating pool

What is chemokinesis?

MigNon-directional movement but speed is increased when chemoattractants are released

What is neutrophil extravasation?

Migration of neutrophils out of the circulation and into the site of tissue damage/infection

Rolling Phase of Extravasation

Neutrophils roll along the endothelial cells while making contact with selectins and adhesive molecules

Adhesion Phase of Extravasation

The release of chemokines that immobilizes the neutrophils

Transmigration Phase of Extravasation

Migration of neutrophils through the blood vessels

Recognition and Attachment Stage of Phagocytosis

Neutrophil receptors will recognize opsonins and attach for opsonization

Ingestion Stage of Phagocytosis

Neutrophils extend pseudopods to surround microbe then engulf it to a phagosome

Killing and Digestion Stage of Phagocytosis

NADPH oxidase will generate reactive oxygen species like H2O2 which is converted into hypochlorite by myeloperoxidase

Oxygen Independent Killing

Digestive Enzymes from granules are released

What are primary granules?

Non-specific azurophilic that contain myeloperoxidase and defensins

What are secondary granules?

Specific to the neutrophil and contains lactoferrin and cytochromes

What are Tertiary granules

Identified using electron microscopy and contain collagenase

What are secretory vesicles

Contains enzymes and other proteins

What is Leukocyte Adhesion Deficiency (LAD)?

Defects in cell adhesion molecules CD11 and CD18 which make them unable to stick to endothelial cells

What is Chronic Granulomatous Disease (CGD)?

X-linked recessive disorder leading to mutation in genes for NADPH oxidase. Neutrophils do not produce H2O2

How does CGD happen?

Tumor like masses of phagocytes (chronic granulomas) formed during inflammation leading to susceptibility for deep tissue infections. It is detectable at birth and can be fatal

What is Myeloperoxidase Deficiency?

Absence of myeloperoxidase leading to impaired killing but it is a benign and asymptomatic condition

What happens in severe G6PD deficieny?

Decreased NADPH production leading to increases susceptibility to severe infections