macrophages and monocytes

what are the goals of macrophages

eliminate insult/pathogen, remove damaged tissue, resolve inflammation, repair tissue, restore function

what are the professional phagocytes

macrophages, neutrophils and dendritic cells

what are neutrophils best at

killing microbes, recruited rapidly, very short lived, constituent of pus

what are macrophages good at

killing microbes if activated, tissue healing, clearance of dead cells, tissue-resident

what are denedritic cells good at

presenting antigens, not good at killing microbes, very rare, reside in tissues

describe the origin of macrophages

haematopoetic stem cells in BM, immature monocytes in BM, mature monocytes in circulation, recruited monocytes in tissue then macrophages in tissue

what is extramedullary haematopoeisis

the production of blood cells outside of the bone marrow

what growth factors are macrophages/granulocytes/dendritic cells dependent on

colony stimulating factor (CSF1 receptor/IL34 in macrophages, CSF3/CSF2 receptor in granulocytes, Flt3 and CSF2 receptor in dendritic cells)

what does CSF1 do

instructs bone marrow to make monocytes, instructs monocyte → macrophage differentiation, signals survival of macrophages and proliferation of macrophages

describe macrophage injury roles

pathogen removal, injury removal, regen and remodelling

describe macrophage chronic disease role

tissue damage, fibrosis, ulceration

describe homeostatic role of macrophages

clearance of apoptotic cells, tissue specific functions

what transcriptional profile does the environment of danger signals and IFN gamma result in

classical activation, TNF alpha and IL-1beta production, NO and ROS production, anti microbial and pro inflammatory

what transcriptional profile does the environment of IL-4/13 result in

alternatively activated, IL-10 and TGFbeta production, TH2 chemokine production, RELMalpha and arginase production, wound repair and anti-inflammatory and anti-worm

what transcriptional profile does the environment of glucocorticoids, apoptotic cells, IL-10 and TGF beta

regulatory, anti inflammatory

what are the populations that contribute to the macrophage pool

tissue resident macrophages, blood monocytes, monocyte-derived macrophages

describe resident macrophages

relatively low in number, sentinels of damage, silent clearance

describe different tissue macrophages

langerhans, alevolar macrophages, kupffer cells, microglia

what is the new dogma for tissue macrophages

most resident cells are long lived and maintained by proliferation

what are the main sources of macrophages in adult murine tissues

yolk sac, fetal monocytes, and adult monocytes

what is the role of macrophages during worm infections

proliferate and maintain tissue homeostasis, influenced by IL-4 and CSF-1

how do macrophages behave in experimental autoimmune encephalitis (EAE)

resident and recruited macrophages contribute to inflammation and may persist post-resolution

what happens to macrophages during influenza infection or peritonitis

recruited macrophages respond to acute infection, remain functionally distinct, and can persist after inflammation resolves

what are classical blood monocytes and their primary function

CD14+ CD16−; they are the majority (80-90%) and are involved in early immune responses and phagocytosis

what characterises non-classical blood monocytes and their role

CD14+ CD16+; they are less abundant (10-15%) and focus on tissue surveillance, repair, and anti-inflammatory responses

what are the ligand receptors for non classical blood monocytes

LFA-1 on monocyte and ICAM-1 on endothelium

what are the ligand receptors for classical blood monocytes

PSGL1 or L selectin on monocytes and P selectin or MadCAM-1 on endothelium

how are classical monocytes short lived precursors

migrate from bone marrow into blood via CCR2, short half life in blood of 20 hours, differentiate to non classical in blood, recruited to replace gut and dermal tissue macrophages in steady state, recruited in large numbers during inflammation

how are non classical monocytes blood macrophages

derived from the classical blood pool, longer half life in blood of 5 days, greater phagocytic capacity than classical monocyte, patrol luminal surface of blood vessel, dependent on LFA-1-ICAM-1, may also be recruited in inflammation

describe how epigenetic changes in macrophages can lead to trained immunity

exposure of macrophages to inflammation leads to epigenetic changes, resulting in different response, eg cells repeatedly stimulated with LPS are tolerised to further stimulation

how can peripheral inflammation alter long term microglia function

they can become tolerised with reduced IL-1beta and IL-6 and IL-12

describe silent clearance of apoptotic cells

prevents inflammation, maintains healthy tissue

what are the triggers of inflammation

LPS, peptidoglycan, beta glucan, ssRNA, alarmins, ATP and DNA from necrotic cell, hyaluronic acid, fibrinogen

which macrophage cleaved cytokines recruit neutrophils

CXCL1, CXCL2, IL-6 cleaved by MMP8 and MMP9

how do liposome-degrading monocytes contribute to the immune response

can process liposomes used for drug delivery, aiding in the resolution of inflammation and enhancing tissue repair mechanisms

what is the overall implication of the study regarding monocytes and arthritis

suggests that classical monocytes facilitate neutrophil recruitment in arthritis, and targeting specific pathways like CCR2 may modulate inflammatory responses and improve therapeutic outcomes

how do formyl peptide receptors (FPRs) facilitate monocyte recruitment

neutrophils release formyl peptides that bind to FPRs on monocytes, triggering their migration toward inflamed tissues

what role does CCL2 play in monocyte recruitment

chemokine that binds to CCR2 on classical monocytes, enhancing their migration from the bloodstream to sites of inflammation

how does azurocidin influence monocyte recruitmen

released by neutrophils, can enhance monocyte adhesion and migration by acting on endothelial cells and modifying the extracellular matrix

what is the function of LL-37 in relation to endothelial cells

acts on endothelial cells to increase permeability (make them "leaky"), facilitating the extravasation of monocytes into inflamed tissues.

how do neutrophil-derived proteases modify chemokines

proteases can cleave and activate chemokine proforms, enhancing their bioactivity and promoting monocyte recruitment

what do vacuolar ATPases do

pump hydrogen ions into phagosome to lower pH

what does NADPH oxidase do

forms oxygen radicals, superoxide, leads to formation of hydrogen peroxide

what does myeloperoxidase do

makes hypochlorite

what does iNOS do

makes NO

what do phagosomes do

starve pathogens by withholding nutrients and transporting metal ions out

how do macrophages clear pathogens

direct killing, antigen presenting activity, antiviral state via IFNa/b

how can classical monocytes clear necrotic tissue

can heal myocardium, can play a role in acute liver injury

what is the key signal for macrophages to stop neutrophil influx

neutrophil apoptosis, uptake of apoptotic neutrophils promotes pro resolution macrophage programme

how do resident macrophages clear apoptotic cells

recognise phosphatidylserine via Tim-4, require MFG-E8 to opsonise and resident macrophages sequester it to restrict apoptotic cell clearance

what happens to PS during apoptosis

flipped outside