Myeloid Cells Flashcards
What are myeloid cells? Which precursor do the system from?
- Monocytes, Macrophages, DCs, Neutrophils, Basophils and Eosinophils.
- HSC –> Common Myeloid Progenitor (CMP)
You can tag CMPs what can you use that for?
- You can tag CMP’s and myeloid cells via different markers in the lab and use that information. I.e. for purifications, checking how far a differentiation/lineage commitment is etc.
Factors affecting (increasing) myelopoiesis
Specific growth factors
• Intracellular and secreted molecules
• Microbial load
• Antibiotics
• Infections
• Probiotics (Will stimulate production of myeloid cells in new born mice for example)
• Obesity (WAT excess increases production)
• Exercise (e.g. via leptin reduction)What structure is created through obesity in regards to myeloids?
- Obesity increases inflammation and you get a “crown” like/ring structure around dead adipose cells by M1 macrophages and CD8+ T cells.
What is Emergency granulopoiesis and why does it happen?
- A systemic infection gives Emergency granulopoiesis because bacteria in the blood will result in G-CSF production from endothelial cells and an increased recruitment.
- Normally there’s a steady state production of granulocytes, in Emergency granulopoiesis a lot is produced.
- Stimulates granulocyte mobilisation by inhibition of Cxcl12, because Cxcl12 normally keeps cells in BM.
How are monocytes produced and how do they circulate?
- Produced in BM –> Blood –> Exit to tissue –> Differentiate from Monocytes to macrophages or DCs
Which two types of monocytes are there?
CD43+
• patrol the vessels and support endothelial cells
Ly6C+ • transmigrate across endothelium into tissue • half-life in blood 1 day • As abundant as DCs in tissue and LNs
What three activities do Monocytes have in tissue in steady state?
• Maintain Mo properties, or
• Upregulate CCR7 (B-,T- Cell and DC maturation) and
migrate to Lymph Nodess, or
• Differentiate into macrophages/DCs
What are the essential functions of macrophages?
Phagocytosis • Microbial killing • Tissue homeostasis/repair • Tissue development • Tissue pathology
Are macrophages all around the body the same?
- No, different tissues will have different types of resident macrophages. Such as:
- Microglia (Brain)
- Kuppfer cells
- Langerhans cells (Gut)
- Red pulp macrophages
When are two specific tissue resident macrophages seeded?
- BEFORE the HSC is created, tissue resident microglia is seeded in the brain also before the brain barrier is created.
- Langerhanns cells are also seeded in development
Hvilke to typer macrofager er der?
M1/M2
M1: Pro-inflammatory
M2: Anti-inflammatory (tissue repair)
What are MDSCs? And what are their functions?
- Myeloid-derived suppressor cells (MDSCs)
MDSC are immature myeloid cells • Defined by a number of markers • None of the markers are unique for MDSC • Suppress T-cells • Two types: M-MDSC and PMN-MDSC
What is the issue of MDSCs?
- MDSCs can hamper the development of myeloid cells that can suppress tumour growth. Since less myeloid cells will attack tumour and less myeloid cells will recruit, activate and prolifferate T-cells.
- Tumors also have an environment in which MDSCs are better activated = less activation of T-cells = more tumour growth.
What is trained immunity?
- That you will respond stronger with your innate immune system at a second exposure to a pathogen, compared to the first time.
- Because of epigenetic reprogramming/imprinting
