Innate immunity II

Question 1

What are the common progenitors for monocytes and granulocytes?

Answer 1

the common myeloid progenitor, the GMP (granular macrophage progenitro).
Dependening on whether G-CSF or M-CSF, will go down the granulocyte lineage (basinophils, eosinophils and neutrophils).
Or will go down the monocyte lineage (M-CSF) to become macrophage (or monocyte derived DC).

Question 2

Where do tissue-resident macrophages come from?

Answer 2

come from yolk sac and foteal liver, as well as monocyte derived (CX3CR1 marker for this).

Question 3

What do monocytes look like?

Answer 3

Large cytoplasm and kidney shaped nucleus.

Question 4

What macrophage tissue-resident cells come from the yolk sac?

Answer 4

Tissue-resident microglia, Kupfer cells (liver) and heart macrophages.

Question 5

What tissue resident macrophages come from foetal liver

Answer 5

lung macrophages, the other tissues like spleen and intestine and skin.

Question 6

whats a moncyte derived marker? and marker of tissue-resident DCs?

Answer 6

CX3CR1. For monocyte derived cells.

CD103+ for tissue resident DCs.

Question 7

What are the major and minor marker and populations of moncotyes? Which is more mature?

Answer 7

CD14 is less mature and the major population. (CD14 coordinate LBP and TLR4 binding).

CD16 (Fc receptor) is minor population and the are more mature.

Question 8

Functions of macrophages in the lungs?
in the liver
and spleen?

Answer 8

In lungs, macrophages can eliminate phathogens dust and allergens.
In liver (kupfer cells), can eliminate pathogens and toxins.
In spleen MZ macrophages elimates blood borne pathogens and senescent RBCs.

Question 9

Functions of macrophages in the intestine, Lymph node and bone?

Answer 9

Clears enteropathogens and promotes tolerance.
LN clears apoptotic T and B cells, and may be involved in antigen transport and presentation to B cells.
In bone, osteclasts resorpbition of tissue and bone remodelling.

Question 10

What are the opsonising receptors on a macrophage?

Answer 10

CD16 (FcR) and CR3 (CD11b CD18), or CR4 (CD11c and CD18)

Question 11

What heterodimers make up LFA-1, Mac-1/CR3 and CR4?

Answer 11

LFA-1 made up of CD11a CD18.
Mac-1 CD3 is CD11b and CD18
CR4 is made up of CD11c andCD18.

Question 12

What are the non opsonic recetors?

Answer 12

CD14/LBP/TLR4
Dectin-1
DC SIGN receptor
Mannose receptors
scavening receptors (M)SR-1/2 recognise oxidised lipids and lipotproteins.
CD36 is a scavening recepotr

Question 13

What does SIRPa detect?

Answer 13

CD-47 whihc is an anti-phagocytic receptor found on live cells and not apoptotic cells.

Question 14

Dectin-1 (has C-type lectin domains), what does it detect?

Answer 14

B glucans, (C-type lectins) recongtino of funig.

Question 15

What does CD91 on macrophges recongise and bind?

Answer 15

Bind to collectins and C1q on apoptotic cells.

Question 16

What other receptors bind apoptotic cells at immune synpase?

Answer 16

Scavenign receptors like CD36 and MARCO, complement recepotrs detect coplement bound. PS recepotor binds PS upregulated on apoptotic cells.

Question 17

Why don’t macrophages induce inflammation against apoptotic cells, but aginst pathogens and necrotic cell?

Answer 17

Necrotic cells produce alarmins that cause inflammation.

Pathogens have PAMPs that are recognised by TLRs that mediate inflammation.

Question 18

What role in development do macrophages play? ANd what else do they play a role in?

Answer 18

In limb foration, and play roles in wound healing, slower if macrophages are depleted.
May help prevent autoimmunity too.

Question 19

What kind of mechanisms of phagocytosis associated with Fc receptors vs CR3?

Answer 19

Changes in actin filaments for phaocytosis or use of clathrin coating.

Question 20

which FcRecepotrs are important for regulation and ADCCs?

Answer 20

Fc gamma ecepors.

Question 21

What do CR1, 2, 3 and 4 all bind?

Answer 21

C3b

Question 22

What complement recepotrs bind iC3b?

Answer 22

CR1, 3 and 4.

Question 23

What complement receptor binds C4b?

Answer 23

CR1

Question 24

What compleemnt recepotrs bind C3d?

Answer 24

CR2,3 and 4.

Question 25

What other complement recepotrs are there? What are they useful for?

Answer 25

C3a and C5a important as chemokines.

Question 26

What two inflammatory pathways do TLR signalling initiate?

Answer 26

NF-kB (and AP-1) and IFNa and B genes.

Question 27

Which TLRs are within intraceullarly compatments?

Answer 27

TLR 3.

And TLR 7,8,9- recognise nucleic acids.

Question 28

What adpator molecules do TLR usse?

Answer 28

Most use MYD88 and IRAK TRAF6 signalling (NF-KB.

TLR3 uses TFIF TRAF3.