Leucopoiesis Flashcards

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
What are stages from stem cell to peripheral blood cell of the neutrophil?
Myeloid Stem Cell, CFU-GEMM, CFU-GM, CFU-G, Myeloblast, Promyelocyte, Myelocyte, Metamyelocyte, Band neutrophil = polynuclear neutrophil.
26
When are primary granules synthesised and what do they compose of?
In the promyelocyte stage - Myeloperoxidase, bacterial permeability inducing factor, lysosome, elastase and acid hydrolases.
27
In acute leukemias where there is mutations in the stem and progenitor cells what is there an increase of?
In blast cells; myeloblastic leukemia - high levels of myeloblasts.
28
What is the colour of the cytoplasm in myeloblasts?
Basophilic - dark purple.
29
What happens to the neutrophil the further it matures?
The nucleus becomes lobed resulting in a segmented neutrophil - held together by strands of chromatin.
30
How is it possible to differentiate between band neutrophils and monocytes?
The band neutrophil is very granular. | Monocyte does not have granules and has many vacuoles.
31
What are CD markers?
These are antigenic markers which are found on all cells in the body but in particular prominent on wbc and wbc precursors.
32
How are CD markers detects?
Via monoclonal antibodies labelled with fluorochromes/fluorescent dyes using flow cytometers.
33
What do CD markers allow us to distinguish?
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
What is the role of the primary granule : myeloperocidase enzyme?
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
What does the primary granule : bacterial permeability inducing factor bind to?
Binds specifically to lipopolysaccharides and therefore exhibits specificity for GN bacteria increasing bacteria membrane permeability and cell death.
36
What is the role of elastase in the primary granules of neutrophils?
This is effective against GN, fungi and enterotoxins.
37
What is the composition of acid hydrolases in the primary granules of neutrophils?
- acid phosphatase - B-galactosidase - B-glucuronidase - esterases.
38
What ceases prior to the formation of secondary and tertiary granules?
Primary granules
39
what do secondary granules provide?
Distinctive staining patterns used in the identification of granulocytes and their precursors.
40
What do secondary granules contain?
Lactoferrin and lysozyme(found in both primary and secondary).
41
What is the role of lactoferrin in the secondary granules of the neutrophils?
It is bacteriostatic and bactericidal.
42
What are the tertiary granules of the neutrophils composed of?
Gelatinase
43
What is gelatines (in tertiary granules) capable of?
Digesting denatured collagen and intact collagen. | This allows neutrophils to migrate through the blood vessel basement membrane and enter the tissue fluid.