Haemopoeisis

Question 1

Which anatomical site is most appropriate for a bone marrow biopsy?

Answer 1

Posterior iliac crest

Question 2

What technique reliably identifies the cell type (lineage)?

Answer 2

Immunophenotyping - an analysis of antigen expression unique to a cell lineage and used to identify the lineage

Question 3

A blood film from a neonate with a normal blood count contains the occassional erythroid and myeloid precursor. What is the cause of this?

Answer 3

Normal for age - occasional precursor in a neonate, particularly pre-term is normal and reflects shifting sites of haemopoeisis in the body whilst in utero

Question 4

What do red cells do?

Answer 4

O2 / CO2 transport

Question 5

What do platelets do?

Answer 5

Primary haemostasis

Question 6

What granulocytes are there?

Answer 6

Neutrophils
Eosinophils
Basophils

Question 7

What do neutrophils do?

Answer 7

Phagocytosis / acute inflammation

Question 8

What do eosinophils do?

Answer 8

Destroy parasites
Modulate hypersensitivity reactions

Question 9

What do basophils do?

Answer 9

Modulate hypersensitivity reactions

Question 10

What do monocytes become?

Answer 10

Macrophages

Question 11

What do monocytes and macrophages do?

Answer 11

Modulate immune reactions
phagocytic clearance
Regulatory functions

Question 12

What lymphocytes are there?

Answer 12

B cells
T cells
Natural killer (NK) cells

Question 13

What do B cells do?

Answer 13

Humoral immunity (antibodies)

Question 14

What do T cells do?

Answer 14

Cell mediated immunity - regulatory functions

Question 15

What do natural killer (NK) cells do?

Answer 15

Antiviral / tumour

Question 16

What is the life span of red cells?

Answer 16

120 days

Question 17

What is the lifespan of neutrophils?

Answer 17

7-8 hours

Question 18

What is the lifespan of platelets?

Answer 18

7-10 days

Question 19

What are the precursors do platelets?

Answer 19

Megakaryocytes

Polyploid platelet precursor

Question 20

What are the precursor to red cells?

Answer 20

Reticulocytes

Gives polychromasia

Question 21

What precursor do neutrophils and blasts are there?

Answer 21

Myelocytes - nucleated precursor between neutrophils and blasts

Question 22

What are blasts?

Answer 22

Nucleated precursor cells

e.g. Erythroblast
Myeloblast

Question 23

Where do precursor cells come from?

Answer 23

Progenitor cells (precursors of precursors)

Question 24

What are the two divisions of haemopoeitic stem cells?

Answer 24

Myeloid
Lymphoid

Question 25

What cells do lymphoid progenitor cells give rise to?

Answer 25

B cells -> plasma cells T cells NK cells

Question 26

What do myeloid progenitor cells give rise to?

Answer 26

Platelets Neutrophils Erythrocytes

Question 27

Describe the cells that myeloid and lymphoid progenitor cells give rise to

Answer 27

Question 28

What are the developmental evens in haemopoeisis?

Answer 28

Self-renewal Proliferation Differentiation Maturation Apoptosis

Question 29

What is self renewal and proliferation?

Answer 29

Self-renewal: property of stem cells, lost in descendants Proliferation: increase in numbers

Question 30

What is differentiation and maturation?

Answer 30

Differentiation - descendents commit to one or more lineages Maturation - descendants acquire functional properties and may stop proliferating

Question 31

What is apoptosis?

Answer 31

Descendents undergo cell death

Question 32

Haemopoeitic stem cells originate from what germinal cell layer?

Answer 32

Mesoderm

Question 33

Circulating committed progenitors are detectable by what week?

Answer 33

Week 5

Question 34

What is the first site of erythroid activity and when does it stop by?

Answer 34

Yolk sac Stops by week 10

Question 35

When does liver start haemopoeisis?

Answer 35

Week 6

Question 36

When does bone marrow start haemopoeisis?

Answer 36

By week 16

Question 37

In adults, haemopoeisis is restricted to what parts of the body?

Answer 37

To the marrow within axial skeleton, pelvis and proximal long bones

Question 38

What are components of bone?

Answer 38

Cellular - Haemopoeitic cells - Non-haemopoeitic cells (e.g. adipocytes, fibroblasts, osteoclasts, osteoblasts) Connective tissue matrix Vascular elements

Question 39

What are venous sinuses of bone marrow?

Answer 39

Nutriient artery and periosteal network Arterioles drain into "sinuses" - wide venous vessels, which open into larger central sinuses In contrast to capillaries, "sinuses" are larger and have a discontinuous basement membrane

Question 40

What are bone marrow sinusoids?

Answer 40

Question 41

How do mature cells get released from marrow?

Answer 41

Formed blood cells can pass through fenestrations in endothelial cells to enter circulation Release of red cells is associated with sinusoidal dilation and increased blood flow Neutrophils actively migrate towards sinusoid Megakaryocytes extend long branching processes called pro platelets into the sinusoidal blood vessels

Question 42

What is the difference between red and yellow bone marrow?

Answer 42

Red - haemopoeitically active Yellow - fatty inactive Increase in yellow marrow as we age, results in reduction in marrow cellularity in older individuals

Question 43

What is the myeloid : erythroid ratio?

Answer 43

Relationship of neutrophils and precursors to proportion of nucleated red cell precursors (ranges from 1.5 : 1; 3.3:1) can change e.g. reversal in haemolysis as a compensatory response

Question 44

What regulates haemopoeisis?

Answer 44

Intrinsic properties of cells e.g. stem cells vs. progenitor cells vs. mature cells Signals from immediate surroundings and periphery (microenvironmental factors) Specific anatomical area ("niche") for optimal developmental signals

Question 45

What regulates haemopoeisis?

Answer 45

Erythroid islands nurse macrophages Neutrophil precursor maturation is regulated by G-CSF (granulocyte-colony stimulating factor) Thrombopoeitin regulaties growth and development of megakaryocytes from their precursors

Question 46

How do we assess haemopoeisis (non lymphoid mature cells)?

Answer 46

Routinely undertaken - blood count, cell indices, morphology Less common - bone marrow examination

Question 47

How do we assess haemopoeisis (mature cells)?

Answer 47

For non-lymphoid cells, the blood count / morphological assessment is often sufficient For lymphoid cells, the expression of antigens indicating lineage or stage of development required - immunophenotyping Cytochemistry is rarely used

Question 48

How do we assess haemopoeitic progenitor / stem cells?

Answer 48

Morphologically indistinguishable cells Rare population of cells - Immunophenotyping - Clonogenic assays - Animal models

Question 49

What is immunophenotyping used for?

Answer 49

Identify patterns of protein (antigen) expression unique to a cell lineage Use antibodies (in combination) specific to different antigens

Question 50

What markers are found on T lymphocytes and haemopoeitic stem cells?

Answer 50

CD3 - T lymphocyte Haemopeitic stem cells - CD34

Question 51

What does flow cytometry do?

Answer 51