Neutrophils Flashcards
peripheral blood circulation half-life
7 hours
main function of neutrophils
phagocytosis
- energy dependent process
Phases of neutrophil phagocytosis
- migration and extravasation
- recognition and attachment
- ingestion
- killing (O2-dependent and O2-independent)
Different types of migration
- chemotaxis
- locomotion
- chemokinesis
What is chemotaxis?
directed movement of phagocytic cells to a site of injury via a concentration gradient of chemostatic substances (chemoattractants)
- picks up low conctn - follows until high conctn
- stimulates change in morph (pseudopods)
Locomotion
random and non-directional
Chemokinesis
non-directional but increases migration speed when chemoattractants are released
migration of neuts out of the circulation and into the site of tissue damage or infection
extravasation
Phases of extravasation
- rolling: along endothelial cells lining blood vessels; contact between neut selectins and endothelial cell adhesive molecules
- adhesion: release of chemokines immobilizes neuts
- transmigration: migration of neuts through the blood vessel wall and into tissues (between or through endothelial cells)
“to prepare for dining”
opsonization
types of granules in neuts for degranulation
- primary: azurophilic, non-specific (lysozyme, myeloperoxidase, proteases, defensins)
- secondary: lilac, specific to neut function (lactoferrin, cytochromes)
- tertiary: electron microscopy (gelatinase, collagenase, membrane glycoproteins)
- secretory: alk phosphatase, complement receptors
oxygen independent killing
- phagosome change in pH (alkaline to neutral)
- degranulation (1 and 2 granules)
- digestive enzymes from granules released = bactericidal molecules and hydrolytic enzymes
hydrolytic enzymes and bactericidal molecules
digestive enzymes from granules released
- lysozyme: hydrolyzes bacterial cell wall
- lactoferrin: removes iron, inhibits bacterial growth
- defensin: kills bacteria, viruses and fungi
Leukocyte Adhesion Deficiency (LAD)
- defect in cell adhesion molecules CD11 and CD18
- unable to stick to endothelial cells of blood vessels and migrate to tissues
- type I, II, and III (degree of severity depends on mutation)
Chediak Higashi
- abnormally large lysosomes (especially in cells that contain granules; melanocytes = albinism)
- WBC have abnormal chemotaxis and degranulation (incr risk of infection)
- large platelet granules (prolonged bleeding)
Chronic Granulomatous Disease (CGD)
- chronic granulomas (tumor-like phagocytes) formed during inflammation
- due to failure of resp burst (O2 dep killing)
- can degranulate at site but can’t kill (little to no O2-, H2O2 or HOCl)
- incr susceptibility to deep tissue and pulmonary infection
- detectable at birth and can be fatal!
- rare; inherited
Myeloperoxidase deficiency
- absence of myeloperoxidase
- impaired killing but benign and mostly asymptomatic (enhances intracellular killing but not absolutely needed)
- autosomal recessive
- function abnormal but infection not serious
severe G6PD def
- decreased NADPH production
- required for O2 dependent killing
- increased susceptibility to severe infections
how do neuts exit circulation?
through diapedesis
Diapedesis
- passage of cells through intact vessel walls
regulated by integrins and selectins on neuts and endothelial cell on the surfaces of blood vessels
Lifespan of neuts in tissues
varies depending on whether infectious or inflammatory agents are present
neutrophil roles as WBC
- innate immune system = protects against infectious agents
- inflammatory response = cytokine + histamine release; increased blood flow and WBC migration
opsonin
any molecule in he plasma which acts on a particle to induce phagocytosis (IgG, IgM, C3b)
T or F. Opsonization is part of the recognition and attachment phase
T!
oxygen-dependent killing
- respiratory burst: after phagosome forms, NADPH oxidase through the HMP shunt generates superoxides
- myeloperoxidase: H2O2 => HOCl/bleach oxidizes bacterial components by halogenation of bacterial cell wall and decarboxylation into an amino acid
- antioxidant mechanisms: to prevent damage to neuts; superoxide dismutase, glutathione peroxidase, catalase
nitroblue tetrazolium stain
- chronic granulomatous diseae
- indirectly detects production of superoxide anion (neut killing ability)
- yellow => blue (when formazan precipitate binds to anions)
- no blue means CGD
