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Origin of blood cells Flashcards

1
Q

Define and describe haematopoiesis

A

β†’It is the formation of blood cells.

β†’STEM CELLS β†’ PROGENITORS β†’ IMMATURE PRECURSORS β†’ MATURE CELLS.

β†’this is a one way process

β†’Throughout the process of making specialised cells from stem cells, growth factors are added throughout.

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2
Q

Give three examples of precursors and the mature cells that they produce

A

β†’ Ξ²-LYMPHOCYTES make PLASMA CELLS

β†’MONOCYTES make MACROPHAGES

β†’MEGAKARYOCYTES make PLATELETS

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3
Q

what are megakaryocytes?

A

megakaryocytes are large polyploid cells which platelets bud off of

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4
Q

What are the different sites of haematopoiesis throughout a human’s lifetime?

A 
β†’IN THE EARLY FOETUS: in the yolk sac 
β†’IN THE FOETUS: in the liver 
β†’IN AN INFANT: throughout the bone marrow 
β†’IN AN ADULT: 
β†’  central skeleton 
β†’ vertebrae 
β†’ribs and sternum
β†’  skull
β†’ sacrum 
β†’ pelvis 
β†’ in the proximal ends of the humerus and the femur
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5
Q

Describe the bone marrow

A

β†’The bone marrow is a spongey, jelly-like tissue.

β†’ It has many blood vessels which bring nutrients and take away new blood cells.

β†’It is a metabolically active, highly innervated organ.

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6
Q

what are the two different types of bone marrow?

A

β†’RED MARROW: where active haematopoiesis takes place

β†’YELLOW MARROW: where it is filled with fat cells

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7
Q

What is the difference between a bone marrow trephine biopsy and a bone marrow aspiration?

A

β†’BONE MARROW TREPHINE BIOPSY: - bone marrow is removed in pieces ( 1 or 2cm core of bone marrow) used to examine the bone marrow architecture

β†’BONE MARROW ASPIRATION: - bone marrow cells are sucked out in a syringe - used to examine cellular morphology

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8
Q

how many red blood cells does adult bone marrow produce?

A

2x10^11 RBC

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9
Q

how many neutrophils does adult bone marrow produce?

A

5x10^10 neutrophils

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10
Q

why is haematopoeisis a one way process?

A

as an anti cancer mechanism

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11
Q

What are the most common cells seen in the bone marrow?

A

β†’ myelocytes and myeloblasts.

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12
Q

Describe the formation of neutrophils (myelopoiesis)

A 
β†’myeloblast
β†’ promyelocyte 
β†’ myelocite 
β†’metamyelocyte 
β†’ band
β†’ segmented neutrophil (Caps ones are more important)
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13
Q

what are the steps of erythropoeisis?

A 
β†’ PROERYTHROBLAST 
β†’ BASOPHILIC ERYTHROBLAST
β†’ POLYCHROMATIC ERYTHROBLAST 
β†’ PYKNOTIC ERYTHROBLAST 
β†’ RETICULOCYTE 
β†’MATURE RED BLOOD CELL 
As we go along, the nucleus shrinks and the cytoplasm gets pinker
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14
Q

what are the steps of platelet formation?

A

β†’ MEGAKARYOBLAST (to the next step, there is only DNA replication, no cell division)
β†’MEGAKARYOCYTE
β†’ BLOOD PLATELETS

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15
Q

what do high level of reticulocytes in the blood mean?

A

β†’ that the bone marrow is working overtime to produce new red cells

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16
Q

what are the steps of lymphocyte formation?

A

β†’STEM CELL
β†’ forms a COMMON LYMPHOID PROGENITOR
β†’ forms either a T-LYMPHOCYTE or a B-LYMPHOCYTE

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17
Q

Where does T-Cell formation occur?

A

β†’ T-Cell formation occurs in the thymus ( in the chest)

β†’ The early progenitor migrates to the thymus and T-Cell receptor gene arrangement occurs

β†’ Positive (check that they work) and negative selection also occur

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18
Q

Where does B-Cell formation occur?

A

β†’B-Cell formation occurs in the bone marrow.

β†’Immunoglobin gene arrangement occurs.

β†’expression of surface IgM (immunoglobulin)

β†’The immature B-Cell migrates to the secondary lymphoid organs (lymph nodes) for maturation and antigen selection.

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19
Q

why are progenitors considered undifferentiated?

A

β†’undifferentiated because you cannot tell the difference between them morphologically
since they don’t show the characteristics of mature cells.

20
Q

why are progenitors considered committed?

A

β†’they are committed to what they will become when they produce mature cells

21
Q

Why are progenitors called Colony Forming Units (CFUs) and how many cells can be in a colony?

A

β†’Progenitors grow to form colonies of mature cells.

β†’ from 32 to hundreds or thousands of cells in a colony.

22
Q

what are some examples of some colony forming units?

A 
β†’ CFU- G granulocyte progenitor 
β†’ CFU- GM granulocyte/monocyte progenitor
β†’ CFU - E erythroid progenitor 
β†’ CFU- bas
β†’ CFU-eo 
β†’ CFU - MK megakaryocyte progenitor
23
Q

why do some erythroid colonies look like they have burst and what are they called?

A

β†’ because they are mobile

β†’ BFU - E (burst forming unit)

24
Q

What are CSFs?

A

Factors which were discovered to stimulate colony growth were named Colony Stimulating Factors or CSFs

25
Q

List some examples of CSFs

A

β†’G-CSF: granulocyte-CSF
β†’ M-CSF: monocyte-CSF
β†’GM-CSF: granulocyte/monocyte-CSF

26
Q

what is G-CSF used for?

A

β†’ used for patients that are not making neutrophils due to chemotherapy

27
Q

what are the steps for bone marrow transplantation?

A

β†’ completely ablate haemopoeisis with radiation and drugs
β†’ infuse compatible donor bone marrow cells
β†’ haemopoeisis can be completely restored

28
Q

what are the requirements for bone marrow transplantation?

A

β†’ donor must be HLA matched (human lymphocyte antigen) could be a sibling or unrelated donor

β†’ or autologous BMT
reinfuse the patients with their own bone marrow

29
Q

what cells can give long term engraftment in bone marrow transplantation?

A

β†’only haematopoietic stem cells can give long term engraftment
β†’not progenitors
β†’ not precursors

30
Q

what are the applications of bone marrow transplantation?

A

β†’ leukaemia, lymphoma, myeloma
β†’ intensified chemotherapy for solid tumors
β†’ thalassemia and SCID

31
Q

what are the risks of bone marrow transplantation?

A

β†’ significant mortality while waiting for engraftment
β†’ infection due to neutropenia (low neutrophil count)
β†’ bleeding due to thrombocytopenia (low platelet count)
β†’Graft versus Host disease (long-term risk in which the graft starts attacking the body)

32
Q

what is the benefit of bone marrow transplantation?

A

β†’ only curative treatment

33
Q

how can haematopoietic stem cells can be described as pluripotent and self-maintaining?

A

β†’ considered pluripotent because they can give rise to cells of every blood lineage.

β†’ considered self-maintaining because a stem cell can divide to produce more stem cells.

34
Q

How did we prove that haematopoietic stem cells are pluripotent?

A

β†’ proved via mice.
β†’Stem cells were marked by retrovirus insertion.
β†’then transplanted into irradiated mice with a small number of stem cells.
β†’The same marked stem cells gave rise to neutrophils, lymphocytes, etc.

35
Q

Describe chronic myeloid leukaemia (CML)

A

β†’Chronic Myeloid Leukaemia (CML) is caused by a chromosome translocation in a stem cell. 9 and 22

β†’excess production of neutrophils and neutrophil precursors

β†’CML mostly affects neutrophil lineage, but the Philadelphia chromosome is also found in T-lymphocytes and other lineages.

36
Q

What cells present the CD34 antigen, and why?

A

β†’Stem cells and early progenitors carry the cell surface antigen CD34.

β†’ used to purify stem and progenitor cells.

37
Q

what are haematopoietic growth factors and what do they do?

A

β†’They are polypeptide growth factors (cytokines).
β†’They bind to the cell surface transmembrane receptors.
β†’They stimulate the growth and survival of progenitors.

38
Q

Describe the specificity of haematopoietic growth factors.

A

β†’some stimulate early progenitors (eg. IL-3, stem cell factors (SCF)
β†’some stimulate late progenitors (eg. M-CSF (monocyte-CSF)
β†’some are specific to one lineage (eg. erythropoietin) β†’some stimulate several different lineages

39
Q

describe erythropoietin

A

β†’produced in the kidney in response to hypoxia. It β†’increases RBC production by increasing the survival of erythroid progenitors (CFU-E).
β†’specific to one lineage (erythroid) and acts on late progenitors.

40
Q

what are the clinical applications of erythropoietin?

A

CLINICAL APPLICATIONS:
β†’ treating anaemia of kidney failure
β†’ an alternative to blood transfusions in Jehovah’s Witnesses

41
Q

Describe G-CSF

A

β†’produced by many cell types in response to inflammation.

β†’acts on mature neutrophils in the periphery.

β†’acts as a chemoattractant

β†’promotes neutrophil maturation

β†’promotes neutrophil activation

β†’It stimulates neutrophil production in the bone marrow.

β†’stimulates neutrophil progenitors (CFU-G)

β†’helps stimulate progenitors of other lineages, but only in combination with other growth factors

β†’mobilizes cells in the bone marrow

42
Q

what are the clinical applications of GCSF?

A

CLINICAL APPLICATIONS:
β†’stimulates neutrophil recovery after bone marrow transplantation

β†’ stimulates neutrophil recovery after chemotherapy

β†’treatment of hereditary (and other cases of) neutropenia (because G-CSF also helps to stimulate other cell lineages, it will also stimulate platelet recovery after bone marrow transplantation)

43
Q

How does G-CSF treatment contribute to Peripheral Blood Stem Cell Transplantation (PBSCT) and how is PBSCT used?

A

β†’G-CSF treatment causes stem cells to be released from the bone marrow into the circulation.

β†’This is seen by the appearance of CD34 on cells in the circulation.

β†’We can collect the stem cells by leukapheresis.

44
Q

why can PBSCT be used as an alternative to bone marrow for transplantation?

A

It’s less traumatic for the donor, as it is so painless that it does not require a general anaesthetic.

45
Q

What is reticulocyte?

A

β†’Immature RBC that just left the bone marrow.

β†’Still has some RNA, ribosomes.

β†’Quickly loses these to make a mature RBC.

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