Neutrophil Function and Phagocyte Disorders

Vocabulary flashcards reviewing neutrophil tissue migration, phagocytosis steps, specific neutrophil dysfunction diseases, and the mononuclear phagocyte system.

Rolling Adhesion

The first step of neutrophil migration where selectins on the inner vessel wall temporarily bind to neutrophil surface molecules, slowing the cell down to roll along the wall.

4 Steps of Phagocytosis

1. Rolling Adhesion: The first step of neutrophil migration where selectins on the inner vessel wall temporarily bind to neutrophil surface molecules, slowing the cell down to roll along the wall.

2. Attachment: chemokines activate integrins on the neutrophil, causing it to bind strongly and stick tightly to the vessel wall and stop moving.

3. Diapedesis: the neutrophil changes shape and squeezes between endothelial cells to exit the blood vessel into the tissue.

4. Migration: the neutrophil follows a concentration gradient of chemokines to reach the site of infection or inflammation through chemotaxis

Integrins

Molecules on neutrophils that, when activated by chemokines, bind strongly to the vessel wall to stop rolling and capture the cell.

Chemotaxis

The process by which a neutrophil moves along a chemical gradient of chemokines and inflammatory signals to reach the exact site of infection.

Opsonization

The process of coating a bacterial cell with molecules such as antibodies, $C3b$, $IgG$, or $CRP$ to make attachment and ingestion by phagocytes easier.

Phagosome

A membrane-bound vesicle formed inside a phagocytic cell after it ingests an antigen.

Phagolysosome

A structure formed inside a phagocyte by the fusion of a phagosome with a lysosome containing digestive enzymes and toxic substances.

Myeloperoxidase (MPO)

An enzyme inside phagocytes that uses hydrogen peroxide ($H_2O_2$) and chloride to produce hypochlorous acid ($HOCl$) for intracellular killing.

Chronic Granulomatous Disease (CGD)

An inherited, severe neutrophil dysfunction caused by a defect in NADPH oxidase, preventing the adequate production of reactive oxygen species (ROS) needed to kill ingested pathogens.

Granuloma

A collection of immune cells surrounding a persistent infection that forms when the immune system attempts to contain microorganisms it cannot completely destroy.

Myeloperoxidase Deficiency

The most common inherited neutrophil disorder, characterized by a lack of myeloperoxidase, leading to a decrease in hypochlorous acid ($HOCl$) and delayed intracellular killing.

Glucose-6-Phosphate Dehydrogenase Deficiency

A condition where decreased G6PD leads to lowered NADPH and reduced glutathione, leaving red blood cells unprotected from reactive oxygen species and causing hemolysis.

Chediak-Higashi Syndrome

An inherited disease caused by a defect in lysosomal and granule trafficking, impairing phagolysosome fusion and producing abnormally large fused granules inside neutrophils.

Mononuclear Phagocyte System

A network of phagocytic cells containing a single nonsegmented nucleus, which includes blood monocytes and tissue macrophages.

Macrophages

Blood/Tissue phagocytes that act as the body's cleanup crew by engulfing old cells, post-inflammation cell debris, and antigen-antibody complexes (These are basically antigens (foreign substances) stuck to antibodies)

5 Steps of Phagocytosis

1. Physical Contact: WBC makes contact with the foreign antigen.

2. Recognition & Attachment: Receptors bind to pathogen markers; opsonization (C3bC3b, IgGIgG, CRPCRP) enhances attachment before the pathogen is ingested into a phagosome.

3. Fusion: Phagosome fuses with a lysosome to form a phagolysosome.

4. Digestion: Digestive enzymes and reactive oxygen species (ROS) like H2O2H2​O2​ and HOClHOCl destroy the pathogen.

5. Excretion: Leftover debris is expelled.