Haematopoieitic lineages Flashcards
What are the 3 blood cells & their function
- Red cells (erythrocytes)
- Function: Oxygen transport
- Platelets
- Function: clotting
- White cells (leucocytes)
- Function: Immunity
What are the 2 categories of white cells
- Myeloid Cells (innate)
- Lymphoid Cells (adaptive)
What are the 3 types of lymphoid cells
- T cells, B cells, NK Cells (natural killer)
What are the 2 classes of myeloid cells
- Monocytes
- Granulocytes: Eosinophils, Basophils, Neutrophils
Where are monocytes made
- bone marrow
Which immune response are monocytes part of (innate or adaptive)
- innate
- Can monocytes migrate
- yes, they can migrate from blood into tissue and become macrophages
What is the key role of monocytes
phagocytosis & cytokine production:
- Engulf and destroy dead host cells and pathogens
- ## Produce IL-2 and IFN gamma which are important for intracellular immunity
which immune response are granulocytes part of (innate or adaptive)
- Innate
what are the 3 granulocytes
- neutrophils
- eosinophils
- basophils
what is the function of neutrophils
- They live in blood for a few hrs then migrate into the tissue where can live for 4-5 days
- They engulf and destroy bacteria (phagocytes).
- Their Granules contain lysosomes and myeloperoxidase – important for pathogen killing
What is the function of eosinophils
- Used in response to parasite infections
- Not Phagocytic
- Associated with allergic disease (release histamine → leaky capillaries → infection)
what is the function of basophils
Associated with allergic disease
which part of the immune system are lymphocytes
adaptive immune system
Function of T cells & where do they develop
- Early progenitors come from bone marrow.
- mature in the thymus
- In the thymus they differentiate and are selected in their ability to recognise antigen and not recognise self
Function of B cells & where do they develop
- Develop in the bone marrow
- They exit the marrow as antigen naïve cells (have not yet recognised antigens)
- Once they have recognised antigens they go and further differentiate in the lymph nodes.
Where do NK cells develop
- bone marrow
describe the structure of platelets
- Platelets have no nucleus (anucleate)
- They have granules which secrete substances that control clotting and the breakdown of a blood clot
- Platelets themselves also form part of a blood clot.
what is the life span of platelets
- 8-12 days
how are platelets removed
removed by macrophages in the spleen and liver
what can low levels of platelets lead to
-Low levels of platelets leads to easy bruising and haemorrhage
what are the other cells produced by haemapotoiesis (2)(outside expected ones)
- dendritic cells
- mast cells
they are not measured in full blood count as they’re found in low number
- where are dendritic cells found
tissues
Function of dendritic cells
- Professional antigen presenting cells found in tissues.
- They detect antigens in the tissue then present it to the innate and adaptive immune system.
Function of mast cells
Produced in the bone marrow but mature in tissues – very similar to basophils
secrete histamine
Where do platelets arise from
- Platelets arise from the cytoplasm of megakaryocytes in the bone marrow.
- Around 2000-3000 platelets are produced per megakaryocyte
- The earliest progenitors of megakaryocytes that look like myeloid blasts.
- The megakaryocytes enlarge due to nuclear divisions (endomitosis)
- This results in an increase in cytoplasmic granulation.
- More granulation results in more platelets produced per MK.
What is endomitosis
Endomitosis isthe replication of chromosomes in the absence of cell ornuclear division, resulting in numerous copies within each cell
how is platelet production regulated
- Platelet production is regulated by thrombopoietin (TPO)
- The TPO receptor (c-Mpl) is found on megakaryoblast, megakaryocyte and platelets
which organ produces TPO - clinical application of this
- TPO is a peptide produced mainly by the liver.
- Therefore, a side effect of liver dysfunction is thrombocytopenia (low blood platelet count) due to lack of TPO production.
- Thrombopoietic GF is used in patients with low platelets to try to stimulate platelet production
Define Haematopoiesis
- The process of blood cell production
when does Haematopoiesis start after fertilisation
Haematopoiesis starts 17 days after fertilisation and continues throughout life in our bone marrow.
how is Haematopoiesis regulated
- Haematopoiesis is regulated by growth factors and cytokines.
- Haematopoietic tissues can respond rapidly to increase cell production e.g. in cases of blood loss, infection etc.
what are the sites of Haematopoiesis in foetus, infants & adults
- Foetus - yolk sack, moving to foetal liver
- Infants - Bone marrow (virtually all bones)
- Adults - Bone marrow of Axial skeleton
describe the Haematopoiesis process
- Haematopoiesis starts with a stem cell
- Stem cells can divide indefinitely so they can
- Replenish themselves
- Give rise to specialised, differentiated cells
- Haematopoietic stem cells (HSC) are multipotent
how is the Haematopoiesis process controlled
- via transcription factors
what are transcription factors
- Transcription factors are proteins that control which genes are turned on or off by binding to DNA and promoting or blocking gene transcription.
what are the 2 types of growth factors
- Early acting GF: act early on in the hierarchy of haematopoiesis
- Examples: Stem cell factor, Flt 3 ligand, IL-3, TPO
- Late acting GF: act late in the hierarchy of haematopoiesis.
- Examples:
- G-CSF and GMCS are important for neutrophil production.
- EPO is used for red cells and TPO for platelets
- Examples:
how is a sample of bone marrow obtained for evaluation & where from
- In order to evaluate haematopoiesis, we need to get access to cells of the bone marrow.
- This is done by a bone marrow biopsy done via a needle.
- Bone marrow taken usually from the iliac crest.
define Erythropoiesis
the haematopoietic pathway for erythrocytes.
describe Erythropoiesis
- It starts in the bone marrow with stem cell.
- The stem cells differentiate and once they reach a Pronomoblast they are committed to the erythrocyte lineage.
- The nucleus in the cells further down the lineage get much smaller until it is extruded in reticulocytes.
- Reticulocytes still have RNA so they can make Hb (not possible in erythrocyte)**
- Reticulocytes differentiate into red blood cells which then pass into circulation.
- If red cells are being destroyed in the periphery, erythropoiesis will be stimulated so there may be lots of precursors – e.g. lots of reticulocytes.
what causes acute leukaemia
- This is where a block in haematopoiesis results in lots of blasts but you do not get the later cells in hierarchy
- Example: acute myeloblastic leukaemia (AML)
what causes chronic myeloid leukaemia
- No maturation-arrest leads to over-production of the mature cells which can also lead to leukaemia.
- In this case there is no negative feedback on hematopoiesis in the system.
- Example: chronic myeloid leukaemia (CML)
what is Agammaglobulinemia & what causes
- X linked Genetic Disorder caused by a block in B cell development
- Stem cells in the bone marrow differentiate into Pro B → Pre B → Immature B → mature B (antigen naïve).
- In Agammaglobulinemia you have defect in a protein called BTK which means you cannot progress from Pre B cell to immature B cell.
- This means in the bone there are lots of Stem cells, Pro B and Pre B but no immature or mature B cells in circulation
- There is also no Ig→ antibodies (produced by B cells).
what is Cytopenia
low cell count
why would someone have low cell count (2)
- Cells are not being produced by the bone marrow centrally (aplastic anaemia)
- Cells are destroyed too quickly in the periphery circulation (immune thrombocytopenia)
how can we increase cell count
- eplace them and/or use growth factors
-
replace them
- Erythrocyte transfusion – lasts 1 month
- Platelet transfusion lasts few days
- Haematopoietic stem cells stem cell transplants should last a life time.
- They are used in patients with immune deficiency or blood cancer. We can remove all their bone marrow via chemotherapy and then repopulate the bone marrow either cells salvaged from individual (autologous) or from a donor (allogeneic).
-
use growth factors
- Erythropoietin (recombinant) – via sub cut injections
- Mainly used for end-stage renal disease
- Aim is to improve anaemia (in renal failure) so transfusions are not needed.
- Regular transfusions are a problem as patient’s can be given too much iron → iron overload → toxic to liver.
- However, EPO is slower than blood transfusion.
- Can also be used in
- Myelodysplasia (when endogenous EPO not increased)
- Pre-autologous blood donation (stimulate red cells)
- Jehovah’s witness (blood loss)
- Sporting Abuse (increase oxygenation of blood)
- G-CSF (recombinant) sub cut injections
- Used for: Prevention of infections in neutropenic (lower normal neutrophils) patients e.g patients on chemotherapy, or patients with congenital neutropenia
- To mobilise stem cells into the peripheral blood for stem cell harvests prior to stem cell transplants
- Thrombopoietin (TPO) receptor agonists
- There are 2 types:
- AMG 531 –sub cut injection (Amgen)
- Eltrombopag –oral –(GlaxoSKB)
- Used for: Thrombocytopenia in myelodysplasia
- Post chemotherapy – maintain/increase platelet count
- There are 2 types:
- Erythropoietin (recombinant) – via sub cut injections
