Innate immunity II Flashcards
What are the common progenitors for monocytes and granulocytes?
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).
Where do tissue-resident macrophages come from?
come from yolk sac and foteal liver, as well as monocyte derived (CX3CR1 marker for this).
What do monocytes look like?
Large cytoplasm and kidney shaped nucleus.
What macrophage tissue-resident cells come from the yolk sac?
Tissue-resident microglia, Kupfer cells (liver) and heart macrophages.
What tissue resident macrophages come from foetal liver
lung macrophages, the other tissues like spleen and intestine and skin.
whats a moncyte derived marker? and marker of tissue-resident DCs?
CX3CR1. For monocyte derived cells.
CD103+ for tissue resident DCs.
What are the major and minor marker and populations of moncotyes? Which is more mature?
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.
Functions of macrophages in the lungs?
in the liver
and spleen?
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.
Functions of macrophages in the intestine, Lymph node and bone?
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.
What are the opsonising receptors on a macrophage?
CD16 (FcR) and CR3 (CD11b CD18), or CR4 (CD11c and CD18)
What heterodimers make up LFA-1, Mac-1/CR3 and CR4?
LFA-1 made up of CD11a CD18.
Mac-1 CD3 is CD11b and CD18
CR4 is made up of CD11c andCD18.
What are the non opsonic recetors?
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
What does SIRPa detect?
CD-47 whihc is an anti-phagocytic receptor found on live cells and not apoptotic cells.
Dectin-1 (has C-type lectin domains), what does it detect?
B glucans, (C-type lectins) recongtino of funig.
What does CD91 on macrophges recongise and bind?
Bind to collectins and C1q on apoptotic cells.
What other receptors bind apoptotic cells at immune synpase?
Scavenign receptors like CD36 and MARCO, complement recepotrs detect coplement bound. PS recepotor binds PS upregulated on apoptotic cells.
Why don’t macrophages induce inflammation against apoptotic cells, but aginst pathogens and necrotic cell?
Necrotic cells produce alarmins that cause inflammation.
Pathogens have PAMPs that are recognised by TLRs that mediate inflammation.
What role in development do macrophages play? ANd what else do they play a role in?
In limb foration, and play roles in wound healing, slower if macrophages are depleted.
May help prevent autoimmunity too.
What kind of mechanisms of phagocytosis associated with Fc receptors vs CR3?
Changes in actin filaments for phaocytosis or use of clathrin coating.
which FcRecepotrs are important for regulation and ADCCs?
Fc gamma ecepors.
What do CR1, 2, 3 and 4 all bind?
C3b
What complement recepotrs bind iC3b?
CR1, 3 and 4.
What complement receptor binds C4b?
CR1
What compleemnt recepotrs bind C3d?
CR2,3 and 4.
What other complement recepotrs are there? What are they useful for?
C3a and C5a important as chemokines.
What two inflammatory pathways do TLR signalling initiate?
NF-kB (and AP-1) and IFNa and B genes.
Which TLRs are within intraceullarly compatments?
TLR 3.
And TLR 7,8,9- recognise nucleic acids.
What adpator molecules do TLR usse?
Most use MYD88 and IRAK TRAF6 signalling (NF-KB.
TLR3 uses TFIF TRAF3.
