The Origin of Blood Cells Flashcards
What is haematopoiesis?
The production of red blood cells, white blood cells and platelets from hematopoietic stem cell
Highly regulated to maintain circulating cell numbers within relatively constant level
Each day the adult bone marrow produces:
~2x10^11 red blood cells
~5x10^10 neutrophils
Plus smaller numbers of other cell types
Requires enormous levels of cell replication
Maintains balance between self-renewal, terminal differentiation, migration and cell death
How does the location/ anatomy of haematopoiesis change through development?
First trimester: Yolk sac Second trimester: Liver & Spleen Third trimester: Central, peripheral skeleton Adulthood: Axial Skeleton Vertebral bones Sternum Ribs Pelvis Haematopoiesis may re-expand to foetal sites in times of severe demand; e.g. thal, MF
What is bone marrow?
Haematopoiesis occurs in BM environment
Spongy jelly like tissue inside the bone
Many blood vessels which bring nutrients and take away new blood cells
Red marrow- active site of haematopoiesis
Yellow marrow- filled with fat cells
What is the overall cellular organisation of haematopoiesis?
Stem cells: Pluripotential or multipotential Progenitor cells Precursor cells Effector cells The red cells, neutrophils and platelets are all effector cells. Which one is produced depends on the type of growth factors that binds to the receptor of the progenitor cells
What are pluripotent stem cells like?
Unlimited self-renewal
Unlimited differentiation- can give rise to any cell type
Present in marrow in small numbers
High resistance to chemotherapy
Resides primarily in marrow- small number in circulation
Can be identified by their CD34+ surface antigen
Look like small lymphocytes
Dysfunction leads to aplastic anaemia or certain leukaemia
What are multipotent stem cells like?
(i.e. lymphoid and myeloid stem cells):
Derived from pluripotential stem cells
Capable of extended self renewal (limited)
Capable of extended differentiation (limited)
Lymphoid stem cells give rise to mature lymphocytes
Myeloid stem cells give rise to red cell, granulocyte and platelets
Lymphoid stem cells can also give rise to lymphoproliferative malignancies if there’s anything wrong with it
Myeloid stem cells can also give rise to myeloproliferative leukaemia
What are progenitor cells like?
Progenitor cells- Colony Forming Units (CFU):
Derived from multipotent stem cells
Capable of limited self renewal
Capable of limited differentiation
CFU-GEMM (granulocytes, erythrocytes, monocytes and megakaryocytes)
CFU-ME (megakaryocytes and erythrocytes)
CFU-GM (granulocytes and monocytes)
CFU-E (just erythrocytes)
Responsive to haematopoietic GFs; e.g. EPO (erythropoietin) stimulates CFU-E
Express differentiation surface antigens; e.g. CD71 (surface antigen) on erythroid progenitor cells
What is the progeny of precursor cells?
First morphologically identifiable cells: Erythroblast Myeloblast Monoblast Lymphoblast Megakaryoblast Little if any self-renewal
What are the mature effector cells?
Red blood cells Neutrophils Monocytes Lymphocytes Platelets
What are the developmental stages of erythropoiesis? (To produce red blood cells)
Multipotent stem cell- CD 34+ Myeloid stem cell Progenitor- BFU-ME Progenitor- CFU-ME Precursor cells are the: Proerythroblast Basophilic erythroblast Polychromatophilic Orthochromatic Reticulocyte Erythrocyte (As it goes along more haemoglobin is being produced therefore the changing colour and the nucleus is getting smaller and smaller until it disappears)
What are the developmental stages of granulopoiesis (neutrophil formation)?
Multipotent stem cells- CD34+ Myeloid stem cell Progenitor- CFU-GM Progenitor- CFU-G Precursors: Myeloblast Promyelocyte Myelocyte Metamyelocyte Band Neutrophil
What are the stages of lymphopoiesis?
Antigen independent phase: Initial lymphopoiesis in bone marrow Maturation occurring in lymph nodes & thymus Antigen dependent phase: 2nd cycle of differentiation & proliferation in response to antigen exposure (differentiation depends on antigen) Memory phase: Follows antigen exposure May live for years Are able to produce antibodies T-cells formation in thymus Early progenitor migrates to thymus T-cell receptor gene rearrangement Positive & negative selection (so the cells not good enough are disposed of) B-cell formation in bone marrow Immunoglobulin gene rearrangement Expression of surface IgM Immature B-cell migrates to 2o lymphoid organs for maturation and antigen selection
What are haematopoietic growth factors and what do they do?
Polypeptide growth factors (cytokines)
HSC are brought in contact with stromal cells
There is cell-cell communication by binding via cell surface transmembrane receptors to secreted cytokines or GF secreted by the stromal cells
Stimulate growth and survival to progenitors
Binding triggers signal transduction, differentiation and apoptosis
What are some types of growth factors?
Some stimulate early progenitors; e.g. Il-3, Stem cell factors (SCF)
Others stimulate late progenitors; e.g. M-CSF (monocyte-colony stimulating factor)
Some are specific to one lineage; e.g. erythropoietin
Others stimulate several different lineages
What is erythropoietin?
Produced in the kidney
In response to hypoxia
Increases red blood cell production by increasing survival of erythroid progenitors (CFU-E)
Specific to one lineage
Acts on late progenitors
Clinical applications of recombinant erythropoietin include:
Treating anaemia from kidney failure
Alternative to blood transfusion in Jehovah’s Witnesses
