Recap of Core Haematology Concepts

Question 1

How is granulopoiesis regulated?

Answer 1

By the action of various growth factors on promyelocytes that determine the lineage it will go down.

Question 2

What growth factor will stimulate a myeloblast to become a neutrophil?

Answer 2

G-CSF (colony stimulating factor)

Question 3

What growth factor will stimulate a myeloblast to become an eosinophil?

Answer 3

IL-5 (interleukin-5)

Question 4

What growth factor will stimulate a myeloblast to become a basophil?

Answer 4

IL-3 (interleukin-3)

Question 5

What growth factor will stimulate a GMP (granulocyte-macrophage progenitor to become a monocyte? (from a common myeloid progenitor but is an agranulocyte).

What is noted about this lineage in monocytes?

Answer 5

M-CSF (colony stimulating factor).

The cells derived from this lineage are macrophage-like monocytes, distinct from typical monocytes that differentiate after migrating to tissues.

Question 6

What progenitor leads to a typical monocyte?
What cytokine will stimulate this?

Answer 6

CMPs (common myeloid progenitors) and CLPs (common lymphoid progenitors), can be acted on by M-CSF to produce Monocyte-dendritic cell progenitors (MDPs), which lead to either dendritic cells or monocytes.

Question 7

What is the most numerous white blood cell? How many cells/L are typically expected?

Answer 7

Neutrophil, with 6x10^9 cells/L

Question 8

How many main types of granules are there in neutrophils? What is contained in them?

Answer 8

There are 2 types of granules, primary and secondary granules.

The primary granules, contain lysozymes and digestive enzymes.

Secondary granules contain lysozymes and collagenase.

Question 9

Why might collagenase be useful in a neutrophils protective role? 2 Points

Answer 9

It allows them to destroy collagen and potentially allow functional tissue to regrow after injury.

Helps in the movement of neutrophils to site of infection, meaning they cant be blocked by collagen.

Question 10

What is the type of reaction produced by neutrophils?

Answer 10

A general, non-specific reaction

Question 11

What is the lifecycle of a neutrophil? 6 Points
Describe the general appearance of each stage.

Answer 11

1. Myeloblast (looks similar to lymphocytes, but granular, nucleoli visible, blue cytoplasm so high RNA content)
2. Promyelocyte (less blue cytoplasm, bigger than myeloblasts, less clear boundary around nucleus, more/darker granules than myeloblast, nucleoli)
3. Myelocyte (less blue cytoplasm, clearer border of nucleus, smaller granules)
4. Metamyelocyte (band beginning to form in nucleus, kidney shaped, still many small granules)
5. Band (Very clear band shape of nucleus. granular)
6. Segment (segmented nucleus, granular)

Question 12

Where do the lineages for

Question 13

How long do neutrophils spend in the peripheral blood? What happens to them after this time?

Answer 13

8-10 hours. After this they pass into peripheral tissues via diapedesis, and within 48 hours will undergo apoptosis.

Question 14

What problems can occur with neutrophils undergoing apoptosis?

Answer 14

Leads to build up of dead neutrophil matter at areas of infection, this can lead to the formation of abscesses which can cause further tissue damage or necrosis.`

Question 15

What receptors are present in neutrophil mediated immunity? (5 Points)

Answer 15

Mannose receptors, which recognise various carbohydrates present on bacteria.

Dectin-1 receptors, detecting fungal beta-glucans which are present in only fungal cell walls.

Toll-like receptor, binds to PAMPs

Complement receptors, which respond to complement a, an anaphylatoxin released in the complement cascade.

Fc receptors, which bind to antibodies on microorganisms to stimulate phagocytosis.

Question 16

What process is first used to kill phagocytosed cells? 1 Point
How does it work, simply? 3 Points.

Answer 16

The respiratory burst, once engulfed, bacteria is held in a vacuole where a cascade of reactive oxygen species are produced.

1. NADPH oxidase donates an electron to oxygen making superoxide, this can decay to hydroxyl radicals.
2. Superoxide dismutase converts O2- to H2O2, another ROS.
3. O2- is converted to O2 in the Haber-Weiss reaction, donating the electron to Fe3+ to make Fe2+, this Fe2+ is used to in the Fenton reaction to convert H2O2 into OH- and a hydroxyl radical.
4. H2O2 is also converted to HOCL (hypochlorous acid, a powerful oxidising agent, by myeloperoxidase.

Question 17

How can some bacteria resist the respiratory burst?

Answer 17

They can produce superoxide dismutase, which converts superoxide (O2.-) into H2O2.
The H2O2 will usually then be dealt with by catalases and peroxidases.

Question 18

Which granules are first to fuse to the bacteria containing vacuole in a neutrophil? What primary role do both the granule types do once fused?

Answer 18

Secondary granules are the first to fuse to the vacuole. These will break down polysaccharides in the cell wall of both gram-positive (peptidoglycan) and gram-negative (peptidoglycan, lipopolysaccharide)

Question 19

How is the neutrophil protected from the respiratory burst?

Answer 19

It is protected by high levels of catalase in its cytosol.

Question 20

What are eosinophils?

Answer 20

Anti-parasitic leukocytes that protect the body by spewing out granule contents at parasites.

Question 21

Roughly, what % of the blood is made up of each of the immune cells? (Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils

Answer 21

Neutrophils: 40-60%
Lymphocytes: 20-40%
Monocytes: 2-8%
Eosinophils: Around 1%
Basophils: >1%

Question 22

How long do eosinophils circulate in the blood?

Answer 22

Around 5 hours, before migrating into peripheral tissues.

Question 23

How long do eosinophils remain in tissues after migrating there? What does this mean for eosinophil presence in tissues? (one tissue in particular)

Answer 23

They will linger for around 14 days, and thus means that eosinophils are highly present under epithelial tissue.

Question 24

Are eosinophils phagocytic?

Answer 24

Yes, but only weakly.

Question 25

What are the 4 main granule contents of an eosinophil?

Answer 25

• Major basic protein (MBP)
• Eosinophil cationic protein (ECP)
• Eosinophil peroxidase (EPO)
• Eosinophil derived neurotoxin (EDN)

Question 26

What eosinophilic growth factors are secreted by T-cells?

Answer 26

IL-4
IL-5
IL-13

Question 27

What other role do eosinophils display in the immune response? (besides anti-parasitic properties). 2 Points.

Answer 27

Eosinophils can help regulate the immune-response. By secreting histaminase, and arylsulfatase (destroys leukotrienes, chemicals only released by the body upon exposure to allergens).

Another function is the weak phagocytic properties, allowing it to recognise and engulf antigen-antibody complexes.

Question 28

What are basophils?
What important receptors do they have on their surface?
What important substance do they secrete?

Answer 28

Leukocytes that are mainly associated with inflammation and anaphylactic responses. Meaning it is responsible in hypersensitivity responses.

They have receptors for both IgE and IgG.

They secrete heparin.

Question 29

What is the role of IgG?
How prevalent in the body is it?
Where is it found?

Answer 29

IgG is the most common immunoglobulin with 75% Ig serum conc.

Mostly associated with secondary response as rapidly produced by memory B cells. Targets pathogens for phagocytosis, helps activate complement system.

Found in blood, lymph and peripheral tissue.

Question 30

What is the role of IgM?
How prevalent in the body is it?
Where is it found?

Answer 30

IgM is the third most common immunoglobulin with around 10% Ig serum conc.

Mostly associated with primary response, as it is presented first without isotype switching of B-cell. Mediates agglutination of pathogens, helps activated complement system.

Mostly found in the blood as in its pentameric form cannot diffuse easily.

Question 31

What is the role of IgA?
How prevalent in the body is it?
Where is it found?
Where is it produced?

Answer 31

IgA is the second most common immunoglobulin, with 15% Ig serum conc.

Main role is to protect mucous membranes by binding to pathogens, preventing attachment and movement through membranes.

Found in mucosal secretions, produced in MALT and other mucosal surfaces.

Question 32

Where are all immunoglobulins produced?

Answer 32

All secreted by plasma cells (or plasmablasts)

Question 33

What is the role of IgD?
How prevalent is it?
Where is it found?

Answer 33

The function of IgD is currently not well understood, but thought to play a role in activating B-cells, as it acts as B-cell surface receptor.

Fourth most common immunoglobulin, with around 0.2% Ig serum conc.

Found on B-cells.

Question 34

What is the role of IgE?
How prevalent is it?
Where is it found?

Answer 34

IgE is the least common immunoglobulin, with 0.002% of Ig serum conc.

IgE is involved in the allergic response and in the defence against parasites. Stimulating the release of histamine and other chemicals from basophils and mast cells.

It is found in low levels in bloodstream, typically more common in tissues around basophils and mast cells.

Question 35

What are monocytes? (Morphology, Lineage, Function)
How long do monocytes circulate in the blood?

Answer 35

The largest leukocytes seen in blood films, with kidney bean shaped nucleus, agranular.

They are agranulocytes despite being derived from myeloid lineage (promonocyte splits from promyelocytes after myeloblast).

Can have different functions depending on the monocyte subset. (classical, intermediate, and non-classical). These range from antigen presentation, to PAMP and DAMP associated phagocytosis, and complement associated phagocytosis. 80-90% of circulating monocytes

After circulating, monocytes migrate to tissues and differentiate into macrophages (majority) or monocyte derived dendritic cells (moDCs).

Typically, monocytes will circulate for around 10 hours before migrating

Question 36

Give some brief details about how different monocyte subsets differ, and their lifecycle. (remember CD presence)

Answer 36

Classical monocytes (CD14++, CD16-), are most present in blood (80-90%), and are most strongly phagocytic, and drawn to immune response stimulation, such as cytokines.

Intermediate monocytes (CD14++, CD16+), are the least common circulating monocyte. Specialise in antigen presentation and cytokine and chemokine secretion. Most likely to migrate into tissues.

Non-classical monocytes (CD14-, CD16++), perform more of a surveillance/protective role, more suited to staying in circulation. Can perform complement mediated phagocytosis.

Question 38

What do B-cells become after they are activated?

Answer 38

They can become plasmablasts, relatively short lived cells that secrete huge amounts of antibodies, and can circulate or reside in secondary lymphoid tissues.

They can also become memory B cells, which circulate, or migrate to tissues where they can live for extended periods of time.

Question 39

What happens to plasmablasts after an infection is over?

Answer 39

A small population of plasmablasts will migrate to bone marrow and transition into Long-Lived Plasma Cells. These cells, accommodated in bone marrow niches survive for a long time. They secrete antibodies into the bloodstream.