Macrophages Flashcards
(26 cards)
How are new immune cells generated
haematopoiesis
what are the 3 major types of pattern recognition receptor
Toll-like
Lectins
Scavenger receptors
what are the major roles of macrophages
pathogen recognition, phagocytosis and killing
secretion of cytokines and antigen presentation to Tcells
tissue remodelling
scavengers of apoptotic cells
what cells are precursors to macrophages
myeloid cells
where are macrophages found
in almost all tissues
how is macrophage heterogeneity created
up regulation of different genes
at what point does macrophage heterogeneity arise
as they differentiate from monocytes
the release of proinflamatory cytokines such as TNF, NO and H2O2 results in which class of macrophage subset
classically activated (M1 macrophage)
what do M1 macrophages do
antimicrobial activity is unregulated such as release of proinflamatory cytokines. they are highly anti-microbial and very good at killing things
alternatively activated Th2 cytokines result in which macrophage phenotype
M2 (wound healing)
what is the role of M2 macrophage
produce polyamide precursors through the conversion of arginine to ornithine which is needed for collagen and matrix regeneration as well as being involved in apoptotic cell clearance
How does TB exploit macrophage heterogeneity to evade the immune system
it skews the immune response towards M2 macrophage allowing it to avoid being killed by antimicrobial M1 macrophage
where are regulatory macrophages primarily found
brain,eye etc i.e. anywhere where inflammation could kill you
what is the role of regulatory macrophages
they down regulate inflammation
which cytokines are released by tissues to cause differentiation to regulatory macrophage phenotype
IL10 and TGF
why does the presence of tumour associated macrophages in cancer result in a poor prognosis
because they produce a number of factors such as VEGF, metalloproteases and EGF which facilitate growth and metastasis. in addition they produce IL10 which suppresses the immune system by inducing differentiation of macrophages to regulatory phenotype
what are the 2 types of macrophage uptake
opsonic and non opsonic
what are the 2 macrophage opsonic uptake models
zipper model- Fc mediated
sinking or splash model- complement mediated
what is the major receptor for opsonic complement mediated phagocytosis by macrophages
C3 receptor
outline the 5 stages of phagocytosis
ligand binding activation of phagocytic cell engulfment internalisation/fusion with lysosomes bacterial killing
after phagocytic uptake in macrophages , what happens to the phagosome
the phagosome matures and gradually acidifies via fusion with endocytic pathway eventually resulting in formation of phagolysosome and bacterial degradation
how does TB block phagosome maturation in macrophages
inhibits sphingosine kinase signalling
what is the fate of phagocytes particles in macrophages
harful antigens are presented on MHC class II molecules
what are the main killing mechanisms of macrophages
reactive oxygen species e.g. NADPH oxidase
proteolytic and hydrolytic enzymes eg lysozymes, pipes and cathepsin D
antimicrobial peptides eg defensins
nutrient deprivation