Basic Concepts - 1B Flashcards
What are macrophages sensors of?
The health of tissues
What type of generalised receptors can macrophages recognise material (soluble and particulate)?
Opsonisation and non-opsonic receptors
Is direct recognition opsonic or non-opsonic?
Non-opsonic
Is indirect recognition opsonic or non-opsonic?
Opsonic
- antibody-Fc receptor
-complement-complement receptor
What are CD200L and SIRP?
Inhibitory receptors
What does SIRP engage?
CD47 and particles that contain CD47 are not phagocytosed for example
What receptor is high affinity for IgG1?
CD64 - highly expressed on macrophages
What do CD64 receptors do very effectively?
Internalise anything opsonised
Are Fc receptors activating or inhibitory?
They can be activating and inhibitory
What is the process of Endocytosis turning acidic?
In endosome, mature into late from early and become more acidic
Then fuse with lysosomes and there will be complete degradation of material
What is a phaogosme combined with a lysosomes called?
Phagolysosomes
Why doesn’t a dendritic cell want to degrade everything?
Wants peptides to be able to deliver to T cells?
What are the microbicidal products of phagocytes?
- acidification
- toxic oxygen derived products
- toxic nitrogen oxides
- antimicrobial peptides
- enzymes
- competitors
What is the microbicidal activity used to make phagosomes as inhospitable as possible?
Toxic species damage bacterial proteins and DNA
Iron pump to remove iron fro phagosome
Antimicrobial peptides
What type of oxidase is responsible for production of radical species?
NADPH oxidase
What is autophagy?
A physiological process involved in the disposal of cytosolic material , relevant in clearance of intracellular pathogens
When do cells undergo autophagy?
In response to infection or nutrient starvation
What is the process of autophagy?
Formation of a double membrane that will embed whatever has triggered it
Then fuses with lysosome and forms an auto lysosome
What is autophagy controlled by?
MTOR
Where are kupffer cells found and what do they do?
Found in the middle of sinusoids filtering everything going through the liver
All macrophages share a particular set of functions but what makes them different between themselves?
Each organ has different environments which dictate different gene expression
What is the difference between macrophages in mucosal tissues and in internal organs?
In mucosal tissues, more exposure to pathogens, higher threshold of activation
In internal organs, lower activation threshold, less exposure to pathogens
What do osteoclasts (type of macrophage) do?
Mediate bone remodelling
What are bone marrow macrophages essential for?
Erythropoiesis
What are involved in brain development through synaptic maturation?
Microglia
What cells mediate iron recycling through erythrophagocytosis?
Kupffer cells and red pulp macrophages (spleen)
What do macrophages make contact with cardiomyocytes through?
Connexin 43 (CX43)-containing gap junctions
How do the gap junctions help macrophages make contact with cardiomyocytes?
Positive charge travels through the gap junction between cardiomyocytes and a macrophage
What are the problems with cardiomyocytes?
Mitochondria can get damaged easily
Contribution of monocytes to maintenance of tissue macrophage populations varies among organs and depends on self-renewal capacity of resident macrophages and accessibility to blood of particular organ… put these in order of macrophage turnover due to blood accessibility.
1) Skin dermis and intestine
2) epidermis, lung and brain
3) spleen and kidney
1) skin dermis and intestine - rapid macrophage turnover , rely on monocyte recruitment
2) spleen and kidney - contain variable percentages of foetal and monocyte-derived macrophages
3) epidermis, lung and brain - low access to blood. Langerhans cells, alveolar macrophages and microglia depend on self-renewal of resident macrophages
Where are all monocytes generated from in adulthood?
Definitive HSC from monocyte-macrophage-dendritic cell progenitors
Where do classical monocytes move to?
Into tissue
What happens to monocytes during inflammation?
Monocyte will be activated and recruited to tissue and differentiate into macrophages that can disappear or maintain cellular replication
What can a dendritic cell activate that macrophages can’t?
Naive T cells
What can both dendritic cells and macrophages both do?
Phagocytosis
Both migrate
What are the two ends of the spectrum of macrophage activation profiles?
M1 - classically activated macrophages
M2 - alternatively activate macrophages
What cytokine do NK cells produce lots of?
Gamma interferon
What do eosinophils and mast cells produce lots of?
Il-4
Are M1 or M2 inflammatory or anti-inflammatory?
M1 - inflammatory, promotes Th1 response
M2 - anti inflammatory promotes Th2 response
What type of cytokines are TNF alpha, IL-6 and IL-1beta?
Inflammatory cytokines
what type of cytokine is IL-10?
Anti-inflammatory, wound healing
What does arginase do?
Dampen immune response
What cells are rich in arginase?
Myeloid suppressor cells
What is in NK cells to enable them to have some memory?
Epigenetic modelling of chromatin, some areas of chromatin have the histone to be modified and more accessible
