macrophages Flashcards
name for liver macrophages
Kupffer cells
function of non immune macrophages
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
function of immune macrophages
cause acute and chronic inflammation
for self defence, especially newly recruited macrophages
for antigen transfer and antigen presentation
development of macrophages
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
spleen macrophages are called
red pulp macrophages
peritoneal cavity macrophages are called
peritoneal macrophages
lung macrophages are called
alveolar macrophages
CNS macrophages are called
microglia
what are monocytes
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
tissue macrophages
well equipped for phagocytosis,
they are large, irregularly shaped with extensive cytoplasm and numerous vacuoles
vacuoles often contain engulfed materials
what affect do growth factors and transcription factors have on macrophages
they determine their fate
transcription factor affect on macrophages
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
growth factor affect on macrophages
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
tissue macrophage function
waste disposal (see notes)
initiation and resolution of inflammation (3 steps and failure)
- pathogen recognition - TLRs and lectins
- inflammatory response - TNF, IL-6, KC, G-CSF
- resolution - TGF-beta, IL-10, lipid mediators
failure = chronic inflam, tissue damage and fibrosis
functions of monocytes
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
what do human toll like receptors do
they allow the detection of different types of infection
what types of receptor do tissue macrophages have
phagocytic and signalling receptors
how is engulfment and degradation by macrophages induced
binding of bacteria to phagocytic receptors
what happens when bacteria binds to signalling receptors on macrophages
induces the synthesis of inflammatory cytokines
what is the macrophages mannose receptor
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
what is Dectin-1 (beta glycan receptor)
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
phagocytosis of antibody opsonised bacteria
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
changes that occur during apoptosis
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
macrophage receptors involved in recognition of apoptotic cells
phosphatidylserine receptors CD14, CD36 scavenger receptor A CD91 and calretuculin complement receptor 3 vitronectin receptor MER tyrosine kinase
consequences of apoptotic cell uptake by macrophages
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
activation of macrophages
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
