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Origins of blood cells Flashcards

1
Q

How many RBCs and neutrophils are produced by adult bone marrow each day?

A
  • RBCs - 2x1011
  • Neutrophils - 5x1010
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2
Q

Define and describe haematopoiesis.

A

Haematopoesis is the production of all types of blood cells.

STEM CELLS produce PROGENITORS (early and late progenitors) which produce IMMATURE PRECURSORS which produce MATURE CELLS.

It is a one way process (only stem cells can go backwards). This is thought to be an anti cancer mechanism to prevent cell damage during replication.

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3
Q

Where does haematopoesis take place?

A
  • In the early embryo it takes place in the york sac (it is in the placenta outside the embryo).
  • In the fetous it happens in the liver,
  • In the infant it happens throughout the bone marrow.
  • In the adult it is limited to the central skeleton - vertebrae, ribs and sternum, skull, sacrum, pelvis, and proximal ends of humerus and femur.
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4
Q

Describe the bone marrow.

A
  • It has a spongy jelly like tissue found inside the bone.
  • It has many blood vessles that bring nutrients and take away new blood cells.
  • So it is highly metabolically active.
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5
Q

What are the two types of bone marrow?

A
  1. Red marrow - site where haematopoesis takes place.
  2. Yellow marrow - Filled with fat cells (thats what gives it the yellow colour).
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6
Q

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

A
  • BONE MARROW TREPHINE BIOPSY :- A bone marrow trephine means that they remove a 1 or 2cm core of bone marrow in one piece - Used to examine the bone marrow architecture.
  • BONE MARROW ASPIRATION :- Bone marrow cells are sucked out in a syringe - Used to examine cellular morphology.
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7
Q

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

A

The most common cells are neutrophil precursors called myelocytes and myeloblasts.

A myelocyte is a young cell of the granulocytic series, occurring normally in bone marrow (may be seen in blood but their presence usually indicates an infection or inflammation).

A myeloblast is an immature blood cell, found in bone marrow, that gives rise to white blood cells of the granulocytic series (neutrophils, eosinophils, and basophils), via an intermediate stage that is called a myelocyte.

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8
Q

Describe the formation of neutrophils (myelopoiesis).

A
  1. MYELOBLAST
  2. promyelocyte
  3. MYELOCYTE
  4. metamyelocyte
  5. BAND
  6. SEGMENTED NEUTROPHIL

(Caps ones are more important)

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9
Q

Describe the formation of red blood cells (erythropoiesis).

A
  1. Proerythroblast
  2. Basophilic erythroblast
  3. Polychromatic erythroblast
  4. Pyknotic erythroblast
  5. RETICULOCYTE - It is an immature RBC that just left the bone marrow. Still has some RNA and ribosomes. Quickly loses these to make a mature RBC.
  6. MATURE RED BLOOD CELL

As we go along, the nucleus shrinks and condenses.

A reticulocyte count measures the number of reticulocytes in the blood. This helps doctors see how many new red blood cells the bone marrow is making.

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10
Q

Describe platelet formation.

A

1) MEGAKARYOBLAST

(to the next step, there is only DNA replication, no cell division)

2) MEGAKARYOCYTE - large, polyploid cell (due to DNA replication)

(Little cytoplasmic fragments break off to form blood platelets)

3) BLOOD PLATELETS

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11
Q

Briefly, describe the formation of lymphocytes (lymphopoiesis).

A
  1. STEM CELL
  2. Forms a COMMON LYMPHOID PROGENITOR
  3. Forms either a T-LYMPHOCYTE or a B-LYMPHOCYTE
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12
Q

Where does T-Cell formation occur?

A
  1. T-Cell formation occurs in the thymus.
  2. The early progenitor migrates to the thymus and T-Cell receptor gene arrangement occurs.
  3. Positive (to check that they work) and negative (to make sure that they dont recognise any self antigens) selection also occur.
  4. If they pass P&N selection they differentiate into mature T cells which are a major part of the immune syatem.
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13
Q

Where does B-Cell formation occur?

A
  1. B-Cell formation occurs in the bone marrow.
  2. Immunoglobin gene arrangement occurs.
  3. There is the expression of surface IgM (immunoglobin M).
  4. The immature B-Cell migrates to the secondary lymphoid organs (such as the lymph nodes) for maturation and antigen selection.
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14
Q

Describe how progenitors are undifferentiated yet still committed.

A
  • They’re undifferentiated in the sense that you cannot tell the difference between them morphologically because they don’t show the characteristics of mature cells.
  • However, they are considered committed in the sense that they’re already committed as to what they will become when they generate mature cells.
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15
Q

How can progenitors be identified using colony assasys?

A
  1. Take a single cell suspension of bone marrow and grow them with growth factors in a semi-solid medium such as agar or methylcellulose.
  2. To grow them you will need to incubate them in a incubator for 7-14 days.
  3. If one of the cells is a pregenitor cell and has the right growth factors it will replicate to produce a colony of mature cells.
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16
Q

Why are progenitors called Colony Forming Units (CFUs)?

A
  • Progenitors grow to form colonies of mature cells.
  • There can be from 32 to hundreds or thousands of cells in a colony.
  • Thus, progenitors are called “Colony Forming Units” or “CFUs”.
17
Q

List some examples of some CFUs.

A
  1. CFU-G: (neutrophilic) granulocyte progenitor.
  2. CFU-GM: granulocyte/monocyte progenitor.
  3. CFU-E: erythroid progenitor.
  4. CFU-Mk: megakaryocyte progenitor.
  5. CFU-bas: basophil progenitor.
  6. CFU-eo: eosinophil progenitor

Early erythroid progenitors (CFU-E) grow to make large colonies that look like they have burst apart. Thus, the name BFU-E (burst forming unit-erythroid) was given.

18
Q

What are CSFs?

A

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

19
Q

List some examples of CSFs.

A
  1. G-CSF: granulocyte-CSF (widely used to promote neutrophill formation in patients that have had chemotherepy).
  2. M-CSF: monocyte-CSF
  3. GM-CSF: granulocyte/monocyte-CSF
20
Q

Briefly, describe the steps towards a bone marrow transplant and what is required of the donor.

A
  1. To treat a patient with incurable leukimea you completely ablate (rub out) haemopoiesis with radiation and drugs. [If you leave them just like that the patients will die after 4 weeks because they cant make any blood cells]
  2. If you infuse the compatible donor bone marrow cells, haemopoiesis can be completely restored (via the donor cells).
  3. The donor must be HLA (Human Leukocyte Antigen) matched (either from a sibling or unrelated donor), or the transplantation can occur via autologous BMT (when you reinfuse the patient with their own bone marrow).
21
Q

What are some situations in which bone marrow transplant can be used?

A
  • Leukaemia, lymphoma, myeloma
  • Intensified chemotherapy for solid tumours
  • Genetic diseases (eg. thalassaemia, SCID)

Lymphoma is cancer that begins in infection-fighting cells of the immune system, called lymphocytes. When you have lymphoma, lymphocytes change and grow out of control.

Myeloma, also known as multiple myeloma, is a blood cancer arising from plasma cells.

Severe combined immunodeficiency (SCID) is a group of very rare, life-threatening diseases that are present at birth. The disease causes the child to have very little or no immune system.

22
Q

List some of the risks and benefits of undergoing a bone marrow transplant.

A

RISKS: -

  • Significant mortality while waiting for engraftment (up to 30 days)
  • Infection could occur due to neutropenia (low neutrophil amount)
  • Bleeding could occur due to thrombocytopenia (low platelet count)
  • Graft versus Host disease (GvHD) - Graft versus host disease (GvHD) is a condition that might occur after an allogeneic transplant. InGvHD, the donated bone marrow or peripheral blood stem cells view the recipient’s body as foreign, and the donated cells/bone marrow attack the body.

BENEFITS: -

  • For many diseases, this is the only curative treatment.
23
Q

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

A
  • They are considered pluripotent because they can give rise to cells of every blood lineage.
  • They are also considered self-maintaining in the sense that a stem cell can divide to produce more stem cells.
24
Q

How did we prove that haematopoietic stem cells are pluripotent?

A
  • This was proved via mice.
  • Stem cells were marked by retrovirus insertion.
  • They were then transplanted into irradiated mice with a small number of stem cells.
  • The same marked stem cells gave rise to neutrophils, lymphocytes, etc.
25
Q

Describe Chronic Myeloid Leukaemia (CML).

A
  • Chronic Myeloid Leukaemia (CML) is caused by a chromosome translocation in a stem cell.
  • CML mostly affects neutrophil lineage, but the Philadelphia chromosome is also found in T-lymphocytes and other lineages.
26
Q

What cells present the CD34 antigen, and why?

A
  • Stem cells and early progenitors carry the cell surface antigen CD34.
  • It’s used to purify stem and progenitor cells.
27
Q

Describe haematopoietic growth factors.

A
  • They are polypeptide growth factors (cytokines).
  • They bind to the cell surface transmembrane receptors.
  • They stimulate the growth and survival of progenitors.
28
Q

Describe the specificity of haematopoietic growth factors.

A
  • Some stimulate early progenitors (eg. IL-3, stem cell factors (SCF))
  • Some stimulate late progenitors (eg. M-CSF (monocyte-CSF))
  • Some are specific to one lineage (eg. erythropoietin - hoemone specifically stimulating the production of RBCs. It is produced in the kidney)
  • Some stimulate several different lineages
29
Q

Describe erythropoietin (including its clinical application).

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

CLINICAL APPLICATIONS: -

  • Treating anaemia of kidney failure.
  • An alternative to blood transfusions in Jehovah’s Witnesses.
30
Q

Describe G-CSF (granulocyte colony stimulating factor).

A
  • It’s produced by many cell types in response to inflammation.
  • It acts on mature neutrophils in the periphery
    • acts as a chemoattractant
    • Promotes neutrophil maturation
    • Promotes neutrophil activation
  • It stimulates neutrophil production in the bone marrow.
    • stimulates neutrophil progenitors (CFU-G)
    • Helps stimulate progenitors of other lineages, but only in combination with other growth factors.
31
Q

What are the clinical applications of G-CSF.

A

CLINICAL APPLICATIONS: -

  • Stimulates neutrophil recovery after bone marrow transplantation.
  • Stimulates neutrophil recovery after chemotherapy.
  • Treatment of hereditary (and other cases of) neutropenia.
  • Because G-CSF also helps to stimulate other cell lineages, it will also (for example) stimulate platelet recovery after bone marrow transplantation.
32
Q

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

A
  • G-CSF treatment causes stem cells to be released from the bone marrow into the circulation.
  • This is seen by the appearance of CD34 on cells in the circulation.
  • We can collect the stem cells by leukapheresis.
  • PBSCT is used as an alternative to bone marrow for transplantation.
  • It’s less traumatic for the donor, as it is so painless that it does not require a general anaesthetic.

FOP (13 decks)

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