Macrophages Flashcards
What are the functions of macrophages
Developmental - apoptotic recognition
Metabolism - Release of adipokines (cytokines secreted by adipose tissues)
Haemtaopoesis - uptake of RBC nuclei and trophic factors
Neurobiology - cross talk with neuronal cells
Acute and chronic inflammation
Self-defense (especially newly recruited macrophages)
Antigen transfer and presentation
Macrophage Development
Derived from yolk sac, doetal liver and bone marrow precursor cells.
What happens to monocytes?
They are released into circulation and can be recruited to tissues for self defence functions or differentiate into tissue macrophages
What are the resident macrophages called
Liver - Kupffer Cells Spleen - Red pulp macrophages Peritoneal cavity - peritoneal macrophages Lung - alveolar macrophages Bone - oestoclasts CNS - microglia
What are the differences between monocytes and macrophages?
Monocytes are smaller and they are the circulatory precusor cells to the macrophages whilst macrophages do phagocytosis and killing of microbes, they also activate T cells and initiate the immune response.
What is Ly6C and how do the differentiate monocytes?
Marker for determining inflammatory monocytes. Ones with Ly6C are inflammatory monocytes, ones without Ly6C are resident or patrolling monocytes
What are the functions of tissue macrophages
Bone marrow + feotal liver = Uptake and degredation of eyrthroid nuclei - failure leads to IFNß production and disruption of hematopoiesis (formation of RBC)
Red pulp macrophages and kuppfer cells = erythrocyte clearance - failure leads to impaired erythrocyte clearance iron recycling
Hoemostatic and inflamed tissues - apoptotic cell clearance - failure leads to uptake of apoptotic material by dendritic cells in the immunogenic context leading to autoimmunity
Lungs - Surfactant clearance - failure alveolar proteinosis
Initiation and resolution of inflammation - pathogen recognition, inflammatory responses and resolution, also recruitment of cytokines –> failure leads to chronic inflammation, tissue damage and fibrosis.
Adipose tissue - WHITE: lipolysis and insulin sensitivity failure - insulin resistance. BROWN: adaptive thermogenesis - failure loss of thingy
Bone - secrete proteins that degrade bone matrix, failure leads to osteopetrosis (bone gets too big)
What happens in the steady state and in disease?
Steady state: Ly6C(low) monocytes roll along endothelial cells and get rid of unwanted things
Danger: Monocyte binds to endothelium and recruits neutrophils to the site leads to EC necrosis and debris scavenging
What type of receptors to macrophages express?
Mannose, LPS, scavenger, CR3, TLR, and scavenger
Name the different types of pattern recognition receptors
Toll-like receptors - 1-10
NOD-related proteins (NOD1, 2, NALP1-3, IPAF, CTIIA, NAIP)
Scavenger receptor A (SR-A)
Lectins - mannose receptor, detetcin 1
What are the changes that occur during apoptosis?
increase in surface PS, chromatin begins to condense, phagocytes recognise surface changes, membrane becomes more irregular, nucleus breaks into smaller condensed bodies –> leakage of cell content
What receptors are involved in phagocytosis and apoptosis
PS receptor (TIM4) CD14 CD36 SR-A CD91 Complement Receptor 3 Vitronectin receptor MER tyrosine kinase
What are the consequences of apoptotic cell uptake via macrophages?
phagocytosis of apoptotic cells by macrophages promotes an anti-inflammatory response, important in preventing macrophage activation and potential triggering of an anutoimmune response Deficiencies: C1q - autoimmunity SAP - autoimmunity MER autoimmunity
How are macrophages activated?
Activated by cytokines derived from themselves or other cells, classical activation is a two step process dependent on priming by interferon-gamma whilst alternative is mediated by TH2-type cytokines IL-4/13. Some cytokines can function to deactivate macrophages (e.g. IL10)
