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30 Cards in this Set
- Front
- Back
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What is the lifespan of neutrophils and erythrocytes?
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-Neutrophils; t1/2 hours
-Erythrocytes; t1/2 weeks |
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What is haemopoiesis?
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Blood cell development which is on ongoing process throughout life
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What are the different lineages stem cells can take?
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-Common lymphoid progenator (CLP)
-Common myeloid progenitor (CMP); which commits to either granulocyte/macrophage progenitor (GMP) and megakaryocyte/erythrocyte progenitor (MEP) lineages |
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At what stage is the lineages is peak proliferation?
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Progenitor stage, increases until reaches terminal proliferation and mature cell
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What cells do common lymphoid progenitor (CLP) differentiate into?
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T-cells and B-cells mostly + Natural killer cells and dentritic cells
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What cells originate from the megakaryocyte/erythrocyte progenitor (MEP)?
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Platelets and erythrocytes
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What cells devleop from granulocyte/macrophage progenitor?
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Granulocytes and macrophages
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What is the consequence of a problem with one step in a lineage?
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If occurs early in process has ability to knock out the production of numerous types of cells
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What meant by oligoclonal?
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The process of stem cell mediated tissue production where only a subset of haemopoeitic stems cells contribute to blood cell production
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Why does only a small amount of stem cells contribute to blood cell production?
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To reserve stem cells and not use them all up
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Where does clonality occur?
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Can occur at initial stage haeopoietic stem cells (HSC) or at the progenitor stage
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What are the two main categories of factors that control haemopoiesis?
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-Stochastic (internal factors eg trascription factors)
-Directed (external factors eg adhesion molecules, cytokines and oxygen) |
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How do external factors control haemopoesis?
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-In bone marrow HSC's interact with stromal and other cells
-They receive signals from direct cell to cell interactions via integrins as well as soluble factors such as cytokines, chemokines and growth factor -Oxygen effects hypoxia inducible factor (HIF) the closer to vessels indicates more expansion and differentiation |
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What is the role of transcription factors in haemopoiesis?
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-Master regulators that control lineage progression
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What are some examples of transcription factors?
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-SCL; HSC's only (not lineage specific
-GATA2; CMP's only -IKAROS; CLP and some lymphoid cells -GATA1; MEPs and erythroid lineage -SPI1; GMP's and come lymphoid cells PAX5; B cells |
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Where do transcription factors bind?
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Bind to specific sequences in the promoter/enhancer gene to regulate their expression
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How do transcription factors regulate transcription?
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-Can either positively or nagatively regulate transcription.
-Each has positive feedback look and may antagonise another transcription factor (GATA1 and SPI1) -Depends on number as to which is produced more |
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How many cytokines and growth factors affect cell proliferation and cell differentiation?
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~20
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What are the main cytokines and growth factors in haemopoiesis?
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-Interleukins (ILs)
-Erythropoietin (EPO) -Thrombopoietin (TPO) -Macrophage colony stimulating factor (M-CSF) -Granulocyte colony-stimulating factor (G-CSF) -Granulocyte/Macrophage colony stimulating factor (GM-CSF) -Stem cell factor (SCF) |
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What is the difference between cytokines/growth factor and transcription factors?
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-Cytokines/growth factor are not master regulators, rather guide cells down particular pathways
-Transcription factor control expression of specific cytokines, growth factors and the receptors -i.e. transcription factor needed to express receptor for cytokine/growth factor to attach and cause effect |
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What is process of STAT transcription factor to regulate survival, differentiation and proliferation?
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-Cytokine binds to receptor on cell wall, binding activates JAK which causes phophorylation of STAT where it travels to the nucleus and activates transcription of their target genes
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Why is STAT transcription process important?
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-Provides negative feedback mechanism to respond to environmental insults such as bacterial invasion or hypoxia
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What are diseases associated with excessive blood cell proliferation?
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(diagram)
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What are diseases associated with deficiency of blood cell production?
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(diagram)
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What are the causes of haemopoeitic diseases?
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-Inherited gene mutations
-Acquired gene mutations -Environmental insults -Interplay between any of the above |
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What classes of genes can be involved in inherated gene mutations?
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-Functional; eg haemoglobin:thalassaemia
-DNA repair -Signalling -Senescence |
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How do acquired gene mutations occur?
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-Acquired during haemopoiesis
-Predominantly associated with neoplasia |
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What gene classes can aquired gene mutations affect?
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All although signalling important because if stuck on can lead to proliferative disease
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What environmental insults cause haemopoietic disease?
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-Infectious agents (virus and bacteria)
-Chemicals/toxins (cytotoxins) -Nutritional (Vit B12/folate deficiency) |
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How do environmental factors act to cause haemopoietic disease?
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-Affect haemopoiesis directly
-Disrupt HSC niche -Facilitate acquired mutations |
