macrophages

Question 1

name for liver macrophages

Answer 1

Kupffer cells

Question 2

function of non immune macrophages

Answer 2

in developmental biology - apoptotic cell clearance
in homeostasis - uptake of aged RBC and iron recycling
in metabolism - release of adipocytokines
in hematopoesis - uptake of RBC in nuclei
in neurobiology - cross talk with neuronal cells

Question 3

function of immune macrophages

Answer 3

cause acute and chronic inflammation
for self defence, especially newly recruited macrophages
for antigen transfer and antigen presentation

Question 4

development of macrophages

Answer 4

dderived from the yolk sac, fetal liver and bone marrow precursor cells
during adult life, monocytes are relseased into circulation and can be recruited to tissues for self defence functions or differentiate into tissue macrophages if an empty niche is available

Question 5

spleen macrophages are called

Answer 5

red pulp macrophages

Question 6

peritoneal cavity macrophages are called

Answer 6

peritoneal macrophages

Question 7

lung macrophages are called

Answer 7

alveolar macrophages

Question 8

CNS macrophages are called

Answer 8

microglia

Question 9

what are monocytes

Answer 9

leukocytes that circulate in the blood, they are bigger than granulocytes and have a distinct indented nucleus
they travel in the blood to tissues where they mature to macrophages and become residnet

Question 10

tissue macrophages

Answer 10

well equipped for phagocytosis,
they are large, irregularly shaped with extensive cytoplasm and numerous vacuoles
vacuoles often contain engulfed materials

Question 11

what affect do growth factors and transcription factors have on macrophages

Answer 11

they determine their fate

Question 12

transcription factor affect on macrophages

Answer 12

PU.1 deficient mice arrested in myeloid development die prematurely with septicemia
Mafb deficient mice lack tissue macrophages
Spi-C deficient mice lack alveolar macrophages

Question 13

growth factor affect on macrophages

Answer 13

M-CSF/CSF-1 deficient mice have reduced no of blood monocytes, reduced osteoclasts and selective loss of tissue macrophage populations
Il-34 deficient mice selectively lack microglia
GM-CSF deficient mice lack alveolar macrophages

Question 14

tissue macrophage function

Answer 14

waste disposal (see notes)

Question 15

initiation and resolution of inflammation (3 steps and failure)

Answer 15

1. pathogen recognition - TLRs and lectins
2. inflammatory response - TNF, IL-6, KC, G-CSF
3. resolution - TGF-beta, IL-10, lipid mediators
   failure = chronic inflam, tissue damage and fibrosis

Question 16

functions of monocytes

Answer 16

source of macrophage precursors
2 subsets = inflammatory - ly6c high, patrolling ly6c low
inflam are rapidly recruited to sites of inflammation
patrolling maintain endothelial cell integrity in blood vessels
monocytes can replace damaged, non-self renewing macrophages in adult life

Question 17

what do human toll like receptors do

Answer 17

they allow the detection of different types of infection

Question 18

what types of receptor do tissue macrophages have

Answer 18

phagocytic and signalling receptors

Question 19

how is engulfment and degradation by macrophages induced

Answer 19

binding of bacteria to phagocytic receptors

Question 20

what happens when bacteria binds to signalling receptors on macrophages

Answer 20

induces the synthesis of inflammatory cytokines

Question 21

what is the macrophages mannose receptor

Answer 21

a type 1 membrane receptor found mainly on macrophages
it is constitutively a recycling receptor
c type lectin with 4 active recognition domains and 4 inactive domains
binds the terminal mannose and fructose on pathogens and host glycans
they are implicated in host defence microbes and virsues

Question 22

what is Dectin-1 (beta glycan receptor)

Answer 22

type 2 membrane receptor found mainly on macrophages, neutrophils and dendritic cells
c type lectin which exhibits specificity for beta glycans
has a non classical ITAM
triggers signalling pathways that lead to the production of proinflam cytokines
triggers the activation of NADPH oxidase and phagocytosis of beta glycan containing yeast
key roles in defence against fungal pathogens

Question 23

phagocytosis of antibody opsonised bacteria

Answer 23

antibody binds bacteria
antibody coated bacteria binds to fc receptors on the cell surface
macrophage membrane surrounds the bacterium
macrophage membranes fuse creating a membrane bound vesicle (the phagosome)
lysosomes fuse with the phagosome creating the phagolysosome

Question 24

changes that occur during apoptosis

Answer 24

healthy cell is challenged
surface PS increases, chromatin begin to condense
membranes become more irregular and the nucleus breaks into smaller condensed bodies
leakage of cell content

Question 25

macrophage receptors involved in recognition of apoptotic cells

Answer 25

phosphatidylserine receptors
CD14, CD36
scavenger receptor A
CD91 and calretuculin
complement receptor 3
vitronectin receptor 
MER tyrosine kinase

Question 26

consequences of apoptotic cell uptake by macrophages

Answer 26

phagocytosis of apoptotic cells by macrophages called efferocytosis
promotes anti-inflammatory response
important in preventing macrophage activation and potential triggering of auto-immune response
deficiency in complement C1q in humans and mice leads to autoimmunity
deficiency in serum amyloid P component leads to autoimmunity
deficiency of MER a receptor tyrosine kinase involved in apoptotic cell uptake leads to autoimmunity

Question 27

activation of macrophages

Answer 27

resting macrophages are not good at killing microbes or tumours
macrophages can be activated by cytokines derived from themselves or other cells especially activated t cells
classical macrophage activation is a 2 step process dependent on priming by TH1 cytokine inferon-y
alternate activation is mediated by TH2 type cytokines IL-4 and IL-13
some cytokines can function to deactivate macrophages