Lecture 2- phagocytes & granulocytes Flashcards
cells develop through hematopoiesis in the _____
bone marrow
hematopoietic stem cells are ___ (several fates)
pluripotent
what is the function of eosinophils?
anti-parasite activity
describe eosinophils
- nucleus is many-lobed
- eosin is the dye that labels granules brightly; acid-loving dye
- granules contain a variety of toxic enzymes & histamine
- best known for combatting multi-cellular parasites or helminths
- make up 1-6% of WBC’s in normal people
main function of basophils
produce cytokine IL-4- major driver of allergic responses
describe basophils
- granules more prone to stain dark purple with basic dyes
- less common- .1-3%
- granules contain histamine, proteoglycans (heparin & chondroitin) and the proteolytic enzymes
- impt. source of the cytokine IL-4 which is central to initiate many allergic responses
- express IgE receptors like mast cells
main activity of mast cells
type I hypersensitivity (allergic) responses, loaded with granules filled with histamine
describe mast cells
- expulsion of parasites from the body by release of granules containing histamine
- doesn’t start but participates more in allergic response
- localized in tissues where they mature
- very similar to basophils, some speculation that mast cells are tissue-localized basophils
- granules contain histamine & heparin
- express receptor of IgE
___ cells activate T cells to initiate the adaptive immune response
dendritic
describe macrophages & dendritic cells
- both phagocytic
- macrophages have bactericidal activity and can present antigens under certain conditions
- dendritic cells are phagocytic, but not known for bactericidal activity
- dendritic cells are “professional antigen presenting cells”
Which 2 granulocytes have the most in common?
basophils & mast cells
describe neutrophils
- poly-morpho nuclear cells (PMN)
- abundant in the blood: 40-70% of leukocytes
- short life span 24 hr half life
- potent killer of pathogens
name the 3 functions of neutrophils
- migrate from blood to sites of infection rapidly
- phagocytosis followed by intracellular degranulation- toxic (granules loaded with degradative enzymes)
- production of reactive oxygen and nitrogen radicals through respiratory burst- NADPH oxidase
describe the function of neutrophils- migration
leukocyte extravasation (diapedesis) is the movement of leukocytes (neutrophils) out of circulatory system and toward sites of inflammation or infection- neutrophils move through vessel in a timed fashion, may make contact with an adhesion molecule, causing them to slow/stop, the sticky endothelium slows down neutrophils and makes them adhere to the vessel and makes them out of the vessel and into the tissue
- major players: adhesion molecules (selectins & integrins) and chemokines
- adhesion molecule: LFA-1 (low and high-affinities)
selectins and integrins are known as _____
adhesion molecules
describe function of neutrophils- phagocytosis & degranulation
- the process of bacterial killing begins with receptor binding, engulfment and phagocytosis (neutrophils express receptors for many bacterial and fungal constituents)
- real killing activity is mobilized when granules fuse with the phagosome (neutrophils find bacteria, engulf them and destroy them with toxic contents of neutrophil granules)
what are the primary and secondary contents of neutrophil granules?
primary: enzymes- degrade bacterial components
defensins- poke holes in bacterial membranes
secondary: lactoferrin- sequester iron away from bacteria
describe function of neutrophil- respiratory burst
(oxidative burst)- when NADPH oxidase is activated and production of bactericidal compounds begin
- NADPH oxidase activation:
.enzymes localized to cell membrane and enzymes localized to cytosol- in resting cell = separate ; upon activation = co-localized
.superoxide, hydrogen peroxide, hypochlorous acid
Where do NADPH oxidase components exist prior to cellular activation?
- in the membrane
- in the cytosol
What are the two toxic byproducts of respiratory burst that are most bactericidal?
hydrogen peroxide
hypochlorous acid
What happens to adhesion molecule LFA-1 to enhance interaction of the neutrophil with the endothelial cell layer?
changes from low to high affinity conformation when the cell receives a chemokine signal (chemokine is a type of cytokine that has chemotaxis- drives cell migration and tells cell to move in a given direction)
describe neutrophil death
apoptosis: taken up by macrophages or exits body as pus
name 3 diseases that arise due to neutrophil function deficiencies
- Leukocyte Adhesion Deficiency (LAD)- as a result of migration not functioning, deficiency in adhesion molecules- infection goes unchecked
- Chediak-Higashi Syndrome- as a result of phagocytosis and granule defects, unable to engulf and kill bacteria
- Chronic Granulomatous Disease (CGD)- no respiratory burst, greatly reduced bacterial killing
