Leucopoiesis Flashcards

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1
Q

What is the shape of a promyelocyte?

A

Circular; as matures a band structure forms.

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2
Q

What is the differentiating factor between band neutrophils and monocytes?

A

Band neutrophils are granular.

Monocytes have vacuoles and lack granules.

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3
Q

What are the growth factors involved with the development of the promyelocyte?

A

Stem cell factors
GM - CSF
G - CSF
Interluekin 3

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4
Q

What is the point of increased granulocyte activity during gestation?

A

after 4-5 months

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5
Q

Where does the transformation of the myeloblast to the mature granulocyte occur?
How long does it take?

A

The myeloblast forms in the marrow, then turns into the mature granulocyte in the peripheral blood
6-10 days.

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6
Q

Which wbc make up the granulocytes?

A

Basophils and eosinophils and neutrophils

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7
Q

Describe the shape/conformation of the mature neutrophil.

A

2-3 times the size of healthy red cell
nucleus divided into 2-5 lobes separated by a thin strand or filament of nuclear filament.
Chromatin lumpy
cytoplasm = pale blue/lilac stained granules

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8
Q

What is the normal reference range for the absolute no. of neutrophils?

A

2 - 7 x10^9/L

40-75% of wbc

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9
Q

What do female neutrophils have that males do not?

A

Females - have small lobe called the drumstick - inactive X chromosome.

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10
Q

What are the 6 enzymes in the pink/lilac staining granules in neutrophils?

A
(ALL HAM)
Acid phosphatase
Lactoferrin
Lysozyme
Hydrolases
Alkaline phosphatase
Myeloperoxidase.
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11
Q

What are mature neutrophils very dependent on in terms of energy?

A

On glycolysis and ATP production

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12
Q

What is the most common leukocyte and where are they?

A

Neutrophil;
Half total blood granulocyte are in the CGP (circulating granulocyte pool)
Remainder are in the marginal pool (MGP)

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13
Q

What is the MGP associated with?

A

The loose adherence of leukocytes to the vascular endothelium and tissues.

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14
Q

How long do neutrophils spend in the blood ?

A

Neutrophils spend only on average 10 hours in the blood before passing into the tissues.

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15
Q

What accelerated the migration of neutrophils from the blood to the tissues?

A

Damage or local inflammation.

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16
Q

What are the 4 ways in which neutrophils play a role in the killing of bacteria and fungi?

A

Chemotaxis
Opsonization/adhesion
Ingestion/phagocytosis
Killing phase

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17
Q

What is the role of chemotaxis and neutrophils in the killing of bacteria?

A

N react to specific chemical stimuli called chemotaxins which direct the neutrophils to the site of infection.

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18
Q

What are the four chemotaxis activations ?

A

coagulation (bleeding)
complement (innate immune response)
fibrinolytic (breaks down fibrin)
Kinin (pain)

19
Q

What is the role of neutrophil opsonization in bacteria killing?

A

This is where the surface of the bacteria is modified to allow neutrophil binding for phagocytosis via specific receptors.

20
Q

What is the role of phagocytosis via neutrophils in bacteria killing?

A

This is the ingestion of the pathogen through enclosing it in a vacuole and eating via enzymes and proteins in the granules to kill the pathogen.

21
Q

What are the main stages and enzymes involved in the killing phase of bacteria by neutrophils?

A

Both oxygen dependent and oxygen independent systems involved.
Different proteins and enzymes, both result in killing bacteria.
Myeloid Peroxidase and lysozyme.

22
Q

Which enzyme(s) are involved in the oxygen dependent system of killing bacteria?

A

Myeloidperoxidase, H2O2 = superoxide and hydroxyl radical formation.

23
Q

Which enzyme(s) are involved in the oxygen independent system of killing bacteria?

A

Direct action of lysozyme - fall in pH to activate, attacks cell wall of bacteria and bactericidal property of cationic proteins from primary neutrophil granules.

24
Q

What molecules are involved in the process allowing neutrophils to bind to their vascular endotheial cells?

A

Integrins and selectins - these facilitate N movement through the vascular endothelial cells to the tissue

25
Q

What are stages from stem cell to peripheral blood cell of the neutrophil?

A

Myeloid Stem Cell, CFU-GEMM, CFU-GM, CFU-G, Myeloblast, Promyelocyte, Myelocyte, Metamyelocyte, Band neutrophil = polynuclear neutrophil.

26
Q

When are primary granules synthesised and what do they compose of?

A

In the promyelocyte stage - Myeloperoxidase, bacterial permeability inducing factor, lysosome, elastase and acid hydrolases.

27
Q

In acute leukemias where there is mutations in the stem and progenitor cells what is there an increase of?

A

In blast cells; myeloblastic leukemia - high levels of myeloblasts.

28
Q

What is the colour of the cytoplasm in myeloblasts?

A

Basophilic - dark purple.

29
Q

What happens to the neutrophil the further it matures?

A

The nucleus becomes lobed resulting in a segmented neutrophil - held together by strands of chromatin.

30
Q

How is it possible to differentiate between band neutrophils and monocytes?

A

The band neutrophil is very granular.

Monocyte does not have granules and has many vacuoles.

31
Q

What are CD markers?

A

These are antigenic markers which are found on all cells in the body but in particular prominent on wbc and wbc precursors.

32
Q

How are CD markers detects?

A

Via monoclonal antibodies labelled with fluorochromes/fluorescent dyes using flow cytometers.

33
Q

What do CD markers allow us to distinguish?

A

If an increase in CD markers in the number of blast cells in the marrow - using flow cytometers and fluorescence dye it can be distinguished between myeloblastic leukemia and acute lymphoblastic leukemia.

34
Q

What is the role of the primary granule : myeloperocidase enzyme?

A

In the non-specific elimination of bacteria, viruses and fungi.
Involved in the conversion of hydrogen peroxide to form hypochlorous acid which has antimicrobial properties.

35
Q

What does the primary granule : bacterial permeability inducing factor bind to?

A

Binds specifically to lipopolysaccharides and therefore exhibits specificity for GN bacteria increasing bacteria membrane permeability and cell death.

36
Q

What is the role of elastase in the primary granules of neutrophils?

A

This is effective against GN, fungi and enterotoxins.

37
Q

What is the composition of acid hydrolases in the primary granules of neutrophils?

A
  • acid phosphatase
  • B-galactosidase
  • B-glucuronidase
  • esterases.
38
Q

What ceases prior to the formation of secondary and tertiary granules?

A

Primary granules

39
Q

what do secondary granules provide?

A

Distinctive staining patterns used in the identification of granulocytes and their precursors.

40
Q

What do secondary granules contain?

A

Lactoferrin and lysozyme(found in both primary and secondary).

41
Q

What is the role of lactoferrin in the secondary granules of the neutrophils?

A

It is bacteriostatic and bactericidal.

42
Q

What are the tertiary granules of the neutrophils composed of?

A

Gelatinase

43
Q

What is gelatines (in tertiary granules) capable of?

A

Digesting denatured collagen and intact collagen.

This allows neutrophils to migrate through the blood vessel basement membrane and enter the tissue fluid.