Lecture 2- phagocytes & granulocytes

Question 1

cells develop through hematopoiesis in the _____

Answer 1

bone marrow

Question 2

hematopoietic stem cells are ___ (several fates)

Answer 2

pluripotent

Question 3

what is the function of eosinophils?

Answer 3

anti-parasite activity

Question 4

describe eosinophils

Answer 4

• 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

Question 5

main function of basophils

Answer 5

produce cytokine IL-4- major driver of allergic responses

Question 6

describe basophils

Answer 6

• 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

Question 7

main activity of mast cells

Answer 7

type I hypersensitivity (allergic) responses, loaded with granules filled with histamine

Question 8

describe mast cells

Answer 8

• 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

Question 9

___ cells activate T cells to initiate the adaptive immune response

Answer 9

dendritic

Question 10

describe macrophages & dendritic cells

Answer 10

• 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”

Question 11

Which 2 granulocytes have the most in common?

Answer 11

basophils & mast cells

Question 12

describe neutrophils

Answer 12

• poly-morpho nuclear cells (PMN)
• abundant in the blood: 40-70% of leukocytes
• short life span 24 hr half life
• potent killer of pathogens

Question 13

name the 3 functions of neutrophils

Answer 13

1. migrate from blood to sites of infection rapidly
2. phagocytosis followed by intracellular degranulation- toxic (granules loaded with degradative enzymes)
3. production of reactive oxygen and nitrogen radicals through respiratory burst- NADPH oxidase

Question 14

describe the function of neutrophils- migration

Answer 14

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)

Question 15

selectins and integrins are known as _____

Answer 15

adhesion molecules

Question 16

describe function of neutrophils- phagocytosis & degranulation

Answer 16

• 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)

Question 17

what are the primary and secondary contents of neutrophil granules?

Answer 17

primary: enzymes- degrade bacterial components
defensins- poke holes in bacterial membranes
secondary: lactoferrin- sequester iron away from bacteria

Question 18

describe function of neutrophil- respiratory burst

Answer 18

(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

Question 19

Where do NADPH oxidase components exist prior to cellular activation?

Answer 19

1. in the membrane
2. in the cytosol

Question 20

What are the two toxic byproducts of respiratory burst that are most bactericidal?

Answer 20

hydrogen peroxide
hypochlorous acid

Question 21

What happens to adhesion molecule LFA-1 to enhance interaction of the neutrophil with the endothelial cell layer?

Answer 21

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)

Question 22

describe neutrophil death

Answer 22

apoptosis: taken up by macrophages or exits body as pus

Question 23

name 3 diseases that arise due to neutrophil function deficiencies

Answer 23

1. Leukocyte Adhesion Deficiency (LAD)- as a result of migration not functioning, deficiency in adhesion molecules- infection goes unchecked
2. Chediak-Higashi Syndrome- as a result of phagocytosis and granule defects, unable to engulf and kill bacteria
3. Chronic Granulomatous Disease (CGD)- no respiratory burst, greatly reduced bacterial killing