Session 3 - Haemopoiesis Flashcards
Where are the haemopoietic stem cells?
Which two progenitor cells do they divide into?
Bone marrow
Common Lymphoid progenitor cell
Common Myeloid progenitor cell
Where does haemopoiesis begin in the embryo?
- Vaculature of the yolk sac
- shifts to embryonic liver by weeks 5-8 in development
Thrombopoiesis creates which cell?
Are these cells nucleated and how many sets of chromosomes do they have?
Platelets
No nucleus
Several sets of chromosomes- polypoid cells
Platelets are polypoid cells. What does this mean?
They have more than 2 sets of chromosomes
Platelets bud off from which cell?
What drives formation of this cell and from what?
megakaryocytes
(TPO) thrombopoietin
drives megakaryocyte formation from the common myeloid progenitor cell
Granulopoiesis forms which cells?
Which are the precursor cells?
basophil eosinophil neutrophil
(‘fill’ with granules)
- Common myeloid progenitor cell
- Myeloblast
When do you see eosinophils in the blood?
Can they phagocytose?
Parasite infection or inappropriately with athsma/ allergy
Yes
How do macrophages protect tissues from pathogens?
Which cells do they derive from?
- phagocytosis
- secrete cytokines
- antigen presentation
Monocytes
(circulate in blood for >3 days)
B and T cells are formed by which process?
How does a B cell mature fully?
Where do the lymphocytes form?
Lymphopoiesis
Exposure to antigen in the lymphocytes which stimulates differentiation into a plasma or memory B cell.
Foetal liver and bone marrow/ thymus
How are the lymphocytes able to recognise so many different antigens?
Rearrangement of the receptor genes
- generates many different receptors each complementary to different antigens
How are common myeloid progenitor cells committed to the erythroid linkage?
What drives development into RBC’s once committed?
expression of transcription factors
- GATA1
- FOG1
- PU.1
EPO, erythropoietin
What stimulates more erythropoietin production?
What type of hormone is it?
What does EPO do?
hypoxia in the blood
glycoprotein hormone
- Protects erythroid cell line from apoptosis (inhibits)
by activating the EPO receptor - Drives RBC formation
How do erythroblasts become mature red blood cells?
- (nucleated) extrude the nucleus and most organelles to form reticulocytes
- Reticulocytes enter circulation
- Extrude remaining organelles, mitochondria and ribosomes
- Become mature RBC’s over 1-2 days
What is measured in the blood to estimate the amount of erythropoiesis occurring?
Explain
Reticulocyte count
Reticulocytes are immature RBC’s and mature quickly (1-2 days). So a low count would indicate no new erythropoiesis is occurring
Why are red blood cells particularly susceptible to oxidative damage?
They have no nucleus so can’t repair damaged proteins
Which cells are affected in pyruvate kinase deficiency?
Explain
Red blood cells
Pyruvate kinase is the last enzyme in glycolysis; it forms pyruvate. All products after the enzyme are reduced (ATP, pyruvate)
The red blood cell has no mitochondria so is reliant on glycolysis as the sole source of ATP.
Why are RBC’s biconcave?
- Optimises the laminar flow properties of blood in large vessels
- deformability through small capillaries
What do RBC’s do?
Exchange gases at the alveoli (O2 & CO2)
What causes hereditary spherocytosis?
Which defect is most common?
Mutations in the genes coding for membrane proteins (ankyrin, spectrin, band 3 protein and protein 4.2) which interact with the cytoskeleton to maintain the biconcave shape of RBC’s
Spectrin mutation
What happens in hereditary spherocytosis?
How can you treat it?
- The RBC’s are sphere shaped instead of biconcave.
- They are prone to lyse because they can’t deform in capillaries- causing haemolytic anaemia.
- They are cleared by the spleen
Splenectomy to reduce the anaemia
Adult haemoglobin has which subunits?
Each subunit is associated with what?
Hameoglobin A - tetramer
alpha2 beta2
A haem group which has Fe2+ at the centre of the porphyrin ring
Hameoglobin takes up how much of the RBC volume?
95%
What is the Bohr effect?
The binding affinity of haemoglobin (for oxygen) is inversely related to CO2 and pH
2, 3 Bisphosphoglycerate
(2, 3 BPG) has what effect on oxygen binding to haemoglobin?
Why?
Reduces affinity for oxygen
BPG is an intermediate of glycolysis so its presence indicates a respiring tissue which needs oxygen
