INTS 2: The Haematopoietic System Flashcards
Define embryonic development
- the beginning of cell and tissue development during embryonic life which covers the period from conception to birth
- this is 21 days in mice and 9 months in humans.
- embryonic development refers more precisely to the initial stages of development in the uterus while we use the term ‘fetal’ development when organs are formed.
Define stem cells
- undifferentiatied cells that can differentiate into specialised cells but also maintain the ability to divide (through mitosis) to produce more stem cells
- found in multicellular organisms
Define bone marrow
- where haemopoietic (haematopoietic) tissue and cells develop
- located in the cavity of some bones, particularly large bones
- e.g. femur and pelvic bones
Define peripheral blood
- the fluid circulating in veins and arteries which carries the main cells that take care of:
- oxygen distribution (red blood cells)
- immunity (lymphocytes)
- antibacterial defence (granulocytes)
- a variety of proteins
- fluids (water) distribution
Define lymphocytes
- cells orginating from the bone marrow, but leave when it reaches maturity and is transferred to the lymphoid tissues
- thymus
- spleen
- lymph nodes
- lymphocytes are counted in their thousands per 100 ml (deciliter) of blood and a normal count is between 1000 and 2500 per 100ml of blood in normal individuals
- they represent 20-30% of the circulating cells in the body
Define lymphocytosis
- an excessive-high number of lymphocytes in the blood
Define lymphocytopenia
- an abnormally low number of lymphocytes in the blood
Define granulocytes
- granule-carrying cells are the primary cell type involved in bacterial and parasite defense
- granulocytes are counted in their thousands per 100 ml (deciliter) of blood and a normal count is between 3000 and 7500 (per 100ml) of blood in normal individuals
- they represent 60-70% of the circulating cells in the body.
Define granulocytosis
- an increased number of granulocytes in peripheral blood
Define granulocytopenia
- a reduced number of granulocytes in peripheral blood
What are the three stages of the development of the haemopoietic system (haematopoiesis)?
- The haematopoietic stem cells originate in the yolk sac and the dorsal aorta
- known as ‘primitive haematopoiesis’ - The liver is then colonised through circulation of cells from 1
- Finally, the bone marrow is established as the definitive site of haemotopoiesis
- Steps 2 and 3 are known as ‘definitive haematopoiesis’
What are the three layers of cells in the developing embryo?
What kind of tissues are derived from each ‘derm’?
- the ectoderm
- the mesoderm
- the endoderm
- study the image to see derived tissues
Describe stage 1 of the development of the haematopoietic system (and the role of the yolk sac)
- the system is derived from the mesoderm layer
- the original pool of haematopoietic stem cells (HSCs) is formed during embryogenesis in a complex process starting in the yolk sac
- then the precursor cells (of endothelial origin) migrate to the dorsal aorta region, then to the placenta and to the foetal liver
- HSCs colonise the bone marrow around the time of birth
Explain how it is evident that the haematopoietic system originated from the yolk sac and later migrate to dorsal aorta etc?
- by looking at the expression of some myelopoietic (bone marrow) genes like RUNX1 (AML1) and NOTCH1
- RUNX1 was expressed in cells in the yolk sac and ventral part of the dorsal aorta
As well as haematopoietic markers, what else is expressed in HSCs?
- they also express endothelial markers
- particularly CD34 (a precursor cell of the haematopoietic lineage) and CD45 (expressed in all nucleated cells)
- these are cluster of differentiation (CD), used to identify the antigens on the surface of cells
Why do HSCs only migrate to the bone marrow around birth and not earlier?
- it requires the bone to be formed
- this involves the differentiation of osteoblasts (bone-forming cells) and chondrocytes (cartilage cells) to help form the supporting structure of the bone marrow
Describe stage 2 of the development of the haematopoietic system: the role of the fetal liver
- Does this stage happen after embryonic development?
- the foetal liver is the primary haematopoietic organ and the main site of HSCs expansion and differentiation during foetal development
- these cells come from the yolk sac
- the liver (along with the spleen) would not necessarily be able to ‘recover’ its ability to produce haematopoietic cells unless it is under stress or in the event of leukaemia
Describe stage 3 of the development of the haematopoietic system: the role of the bone marrow
- this is a very late stage in the HSC development because the bones need to develop before the bone marrow can populate them
- specialised niches formed in the bones will accommodate the HSCs
- their progeny (descendants) will undergo lineage differentiation to develop red blood cells, myeloid and lymphoid progenitors
- all this occurs through the vascular invasion into the developing bones
- facilitating circulation and the seeding of haematopoietic progenitor cells
Is the fetal liver equivalent of bone marrow in adult life?
- yes
How are endothelial cells important players in helping to establish HSCs?
- HSCs are derived from niches of cells derived from endothelial cells of the dorsal aorta
Where is the main site of haematopoietic cell production after birth?
- the bone marrow
- because it contains haematopoietic stem cells (HSCs)
What are the two characteristics unique to stem cells?
- they have the pluripotent capacity to differentiate into a variety of cell lineages
- and they can do so while retaining a ‘self-renewal’ ability
What cells can haematopoietic stem cells (HSCs) differentiate to?
- white blood cells (leukocytes)
- red blood cells (erythrocytes)
- platelets (thrombocytes)
Describe the structure and anatomy of the bone marrow
- it is a highly vascularized tissue with a complex spongy structure
- the blood vessels are the pathway used by HSCs to migrate from the liver during foetal life to populate this tissue
What other types of cells present in the bone marrow apart from the haematopoietic cells and their precursors?
- stomal cells
- adipocytes
- bone matrix
- endothelial cells (forming the blood vessels)
What procedure would you perform to analyse the different cellular components of bone marrow?
- bone marrow aspiration
Briefly describe how bone marrow aspiration is performed
- where
- how
- it is taken from large bones, such as the iliac crest
- other sites with a lot of BM may not be easily accessible or be close to nerves, muscles etc
- adults usually undergo local anaesthetic and children under general
Describe the bone marrow aspirate
- what cells are present?
- there is a mixture of immature and mature cells if the main lineages
- immature cells are generally referred to as X-blasts
- mature cells are referred to as X-cytes
Observe the main lineages of cell maturation in the bone marrow
Which is normal and which is leukaemic bone marrow aspirate?
- in leukaemic bone, all cells look exactly the same
What hormones control haematopoiesis?
- a variety of growth hormones specific for each lineage:
1. Erythropoietin (EPO): - a hormone secreted by the kidneys that increase the production of red blood cells
- acts in response to falling blood oxygen levels or haemorrhages
2. Granulocyte-colony stimulating factor (GCSF), also known as colony-stimulating factor 3: - it is a glycoprotein that stimulates the bone marrow to produce granulocytes and myeloid stem cells and release them into the bloodstream
- G-CSF is produced by the endothelium, macrophages and a number of other immune cells
3. Thrombopoietin (TPO): - a glycoprotein hormone made by the liver and kidneys
- stimulates the production and differentiation of megakaryocytes, which are the bone marrow cells that bud off large number of platelets
How is lymphocyte production controlled?
- instead of a hormone, lymphocytes receive stimulatory signals from other cells
- so they are the most difficult cells to ‘push’ to grow
- they can only develop from precursor lymphoid cells