Macrophages

Question 1

How are new immune cells generated

Answer 1

haematopoiesis

Question 2

what are the 3 major types of pattern recognition receptor

Answer 2

Toll-like
Lectins
Scavenger receptors

Question 3

what are the major roles of macrophages

Answer 3

pathogen recognition, phagocytosis and killing
secretion of cytokines and antigen presentation to Tcells
tissue remodelling
scavengers of apoptotic cells

Question 4

what cells are precursors to macrophages

Answer 4

myeloid cells

Question 5

where are macrophages found

Answer 5

in almost all tissues

Question 6

how is macrophage heterogeneity created

Answer 6

up regulation of different genes

Question 7

at what point does macrophage heterogeneity arise

Answer 7

as they differentiate from monocytes

Question 8

the release of proinflamatory cytokines such as TNF, NO and H2O2 results in which class of macrophage subset

Answer 8

classically activated (M1 macrophage)

Question 9

what do M1 macrophages do

Answer 9

antimicrobial activity is unregulated such as release of proinflamatory cytokines. they are highly anti-microbial and very good at killing things

Question 10

alternatively activated Th2 cytokines result in which macrophage phenotype

Answer 10

M2 (wound healing)

Question 11

what is the role of M2 macrophage

Answer 11

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

Question 12

How does TB exploit macrophage heterogeneity to evade the immune system

Answer 12

it skews the immune response towards M2 macrophage allowing it to avoid being killed by antimicrobial M1 macrophage

Question 13

where are regulatory macrophages primarily found

Answer 13

brain,eye etc i.e. anywhere where inflammation could kill you

Question 14

what is the role of regulatory macrophages

Answer 14

they down regulate inflammation

Question 15

which cytokines are released by tissues to cause differentiation to regulatory macrophage phenotype

Answer 15

IL10 and TGF

Question 16

why does the presence of tumour associated macrophages in cancer result in a poor prognosis

Answer 16

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

Question 17

what are the 2 types of macrophage uptake

Answer 17

opsonic and non opsonic

Question 18

what are the 2 macrophage opsonic uptake models

Answer 18

zipper model- Fc mediated

sinking or splash model- complement mediated

Question 19

what is the major receptor for opsonic complement mediated phagocytosis by macrophages

Answer 19

C3 receptor

Question 20

outline the 5 stages of phagocytosis

Answer 20

ligand binding 
activation of phagocytic cell
engulfment
internalisation/fusion with lysosomes
bacterial killing

Question 21

after phagocytic uptake in macrophages , what happens to the phagosome

Answer 21

the phagosome matures and gradually acidifies via fusion with endocytic pathway eventually resulting in formation of phagolysosome and bacterial degradation

Question 22

how does TB block phagosome maturation in macrophages

Answer 22

inhibits sphingosine kinase signalling

Question 23

what is the fate of phagocytes particles in macrophages

Answer 23

harful antigens are presented on MHC class II molecules

Question 24

what are the main killing mechanisms of macrophages

Answer 24

reactive oxygen species e.g. NADPH oxidase
proteolytic and hydrolytic enzymes eg lysozymes, pipes and cathepsin D
antimicrobial peptides eg defensins
nutrient deprivation

Question 25

how does shigella evade macrophage killing

Answer 25

inhibits antimicrobial peptides to prevent them from forming pores in it’s membrane

Question 26

give examples of possible detrimental diseases caused by under or over activity of macrophages

Answer 26

neurodegeneration, osteoporosis, atherosclerosis, fibrosis, cancer, obesity and diabetes, arthritis