Session 3: Blood cells and haematopoiesis

Question 1

What is haematopoiesis?

Answer 1

The process of producing mature blood cells from precursor cells

Question 2

Where does haematopoiesis occur in the second trimester?

Answer 2

From the second trimester, haematopoiesis primarily occurs in the liver.

Question 3

Where does haematopoiesis occur in the third trimester?

Answer 3

From the third trimester, haematopoiesis primarily occurs in the bone marrow.

Question 4

Where does haematopoiesis occur in adults?

Answer 4

Bone marrow of the sternum, pelvis, vertebrae, ribs and skull.

Question 5

Where does haematopoiesis occur in the foetus?

Answer 5

The liver and spleen

Question 6

Describe the features of erythrocytes (RBCs)

Answer 6

Anucleate cells densely filled with haemoglobin - have no organelles. Flexible, biconcave discs with a diameter of ~7.2uM (x2 diameter of narrowest capillaries). Large surface area for gaseous exchange for delivering oxygen to tissues and returning carbon dioxide to lungs.

Question 7

What is the progenitor of erythrocytes?

Answer 7

Myeloid stem cell

Question 8

What is the process of production of erythrocytes?

Answer 8

Erythropoiesis

Question 9

What controls erythropoiesis?

Answer 9

• An imbalance in homeostasis of blood oxygen levels and** acidity of the blood acts as a stimulus** = hypoxia due to decreased RBC count, decreased amount of haemoglobin, or decreased availability of oxygen.
• This leads to reduced oxygen in the blood.
• The kidney (and liver) then releases erythropoietin in response.
• The erythropoietin stimulates red bone marrow to enhance erythropoiesis and increase the RBC count as a result.
• The increased RBC count leads to increase of oxygen carrying capacity of the blood.

Question 10

Describe the features of platelets?

Answer 10

• Platelets are anucleate 2-3uM cell fragments derived from bone marrow megakaryocytes. - They contain a range of factors which are important for blood clotting and vessel wall repair.

Question 11

What is thrombopoiesis?

Answer 11

Thrombopoiesis is the formation of thrombocytes in the bone marrow.

Question 12

What is the main regulator of thrombopoiesis?

Answer 12

Thrombopoietin hormone (TPO)

Question 13

Where is thrombopoietin produced?

Answer 13

By the liver and kidneys

Question 14

How does thrombopoietin (TPO) work?

Answer 14

TPO acts in the bone marrow to stimulate megakaryocytes to increase in size = by undergoing DNA replication without dividing
- Platelets ‘bud off’ or ligate from enlarged cells
- TPO can bind to platelets, where it is destroyed = this reduces the bioavailability of the hormone as the platelet numbers rise.

Question 15

What is innate immunity?

Answer 15

An immediate, yet non-specific and transient response to infection.

Question 16

What is adaptive immunity?

Answer 16

• Humoral responses involve secretion of immunoglobulins (antibodies) by B cells.
• Cell-mediated responses involve the killing of infected cells by T cells.

Question 17

What are neutrophils?

Answer 17

Question 18

Where do neutrophils develop?

Answer 18

Neutrophils develop in the bone marrow.

Question 19

What are eosinophils?

Answer 19

Question 20

In what tissue are abundant eosinophils found?

Answer 20

Eosinophils are abundant in the connective tissue of the intestinal lining and in the lungs of asthma patients.

Question 21

What are basophils?

Answer 21

Question 22

What are monocytes?

Answer 22

Account for 2-10% of total WBC. Lifespan varies (days). Phagocytic and pinocytic. Monocytes are ‘agranulocytes’ that leave circulatory system by diapedesis and mature into macrophages in tissues. 15-20uM diameter. Large, kidney-shaped nucleus. Fine cytoplasmic granules contain lysosomes. Function: respond to inflammation and act as antigen-presenting cells (APCs).

Question 23

What are macrophages?

Answer 23

Lifespan of several years. Derived from circulating monocytes which migrate to loose connective tissue.

Function: respond to local inflammation and phagocytic (degrade foreign organisms/cell debris). Professional antigen presenting cells (APCs) which present foreign materials to T-lymphocytes.

Question 24

What is adaptive (or acquired) immunity divided into?

Answer 24

1. Humoral immunity: secretion of immunoglobulins by B lymphocytes into extracellular fluids (humours).
2. Cell-mediated immunity: T lymphocyte-mediated destruction of infected cells (via cytotoxic lysozymes).

Question 25

What are lymphocytes?

Answer 25

White blood cells which constitute 20-50% of circulating leukocytes. 5-20uM in diameter. Appear spherical in histological preparations with thin strip of cytoplasm surrounding large but regularly shaped nucleus. B and T lymphocytes.

Question 26

How do erythrocytes survive if they have no organelles?

Answer 26

They get their **energy from glycolysis** in the cytoplasm (make ATP using glucose - does not involve mitochondria).

Question 27

What is the function of B lymphocytes?

Answer 27

B lymphocytes shuffle DNA encoding their immunoglobulins to create a range of antibodies able to recognise a range of antigens.

Question 28

What does a B cell do if presented to a foreign antigen it recognises?

Answer 28

The B cell will **proliferate** under the control of T-helper cells - to form a population of **plasma cells that will produce antibodies specific for that antigen**.

Question 29

What is the name given to B lymphocytes which are able to expand again following re-exposure to the same antigen?

Answer 29

Long-lived memory B lymphocytes.

Question 30

What are T lymphocytes?

Answer 30

Lymphocytes that originate in the bone marrow but mature in the thymus (or spleen in adults). They undergo rearrangement of their T cell receptor genes. T lymphocytes are made up of CD4+ (T helper) cells and CD8+ (T cytotoxic) cells.

Question 31

What is the function of CD4+ (T helper) cells?

Answer 31

CD4+ T-helper cells induce proliferation and differentiation of T and B cells and activate macrophages.

Question 32

What are mast cells?

Answer 32

They appear like basophils but are derived from a DIFFERENT precursor. Components of the innate immune system but also play role in allergy. Granules contain: heparin (anticoagulant), histamine (increase blood vessel wall permeability) and cytokines (to attract eosinophils and neutrophils).

Question 33

Where can mast cells be found?

Answer 33

Connective tissue.

Question 34

What is the function of CD8+ (T cytotoxic) cells?

Answer 34

CD8+ T-cytotoxic cells induce apoptosis in virally-infected cells by creating holes in the plasma membrane with perforin and injecting granzymes which degrade the cell.

Question 35

What is the name given to the pathological response resulting from mast cell hypersensitivity?

Answer 35

Type 1 hypersensitivity. This is stimulated by allergens. Responses can be localised (allergy) or systemic (anaphylaxis).

Question 36

Describe the process of type 1 hypersensitivity resulting from mast cell hypersensitivity?

Answer 36

Following initial exposure, mast cells become coated with immunoglobulin E (IgE) molecules that specifically bind allergens. When an allergen cross-links these surface-bound IgE molecules, the contents of the granules are rapidly released from the cell.

Question 37

Describe structure/function of RBC (erythrocytes)

Answer 37

Structure: anucleate cells, specialised for mechanical flexibility, 120-day lifespan, contain concentrated haemoglobin. Function: oxygen and carbon dioxide carriage.

Question 38

Describe structure/function of neutrophils

Answer 38

Structure: end cells; cannot re-enter blood. Numerous granules with proinflammatory and antibacterial products. Phagocytose and kill bacteria. Function: **inflammation and defence against bacteria**.

Question 39

Describe structure/function of eosinophils

Answer 39

Structure: **end cells; cannot re-enter blood**. Numerous granules with proinflammatory and anti-parasite products. Function: **Inflammation, allergy defence and defence against parasites**.

Question 40

Describe structure/function of basophils

Answer 40

Structure: end cells; cannot re-enter the blood. Numerous granules with proinflammatory products. Function: Inflammation, allergy and defence against parasites.

Question 41

Describe structure/function of monocytes

Answer 41

Structure: can mature into macrophages - including becoming long-term tissue macrophages. Ingest organisms (phagocytosis) and debris. Major cytokine producers. Function: Inflammation and defence against infections.

Question 42

Describe structure/function of lymphocytes

Answer 42

Structure: after formation can proliferate in tissues and lymph nodes and recirculate through the blood. Function: adaptive immune system.

Question 43

Describe structure/function of platelets (thrombocytes)

Answer 43

Structure: cell fragments produced by fragmentation of megakaryocyte cytoplasm - major source of growth factors at sites of injury. Function: blood clotting (haemostasis).

Question 44

Which one of the following most accurately describes the functions of mast cells? A) Phagocytosis B) Immunoglobulin production C) Killing of virally-infected cells D) Local inflammation, innate immunity, tissue repair E) Antigen presentation

Answer 44

D) Local inflammation, innate immunity, tissue repair.

Question 45

What is the function of 'chemotactic factors' produced by mast cells?

Answer 45

Recruiting immune cells, particularly eosinophils and neutrophils.

Question 46

What is the function of 'histamine' produced by mast cells?

Answer 46

Increase vascular permeability.

Question 47

What is the function of 'cytokines' produced by mast cells?

Answer 47

Modulators of immune cell activity.

Question 48

What is the function of 'heparin' produced by mast cells?

Answer 48

Anti-coagulant.

Question 49

From which immune cell type do macrophages develop?

Answer 49

Monocytes.

Question 50

Where do macrophages mature?

Answer 50

In organs such as the skin and liver.

Question 51

Arrange these blood components according to life span length with 1 being the shortest and 4 being the longest: RBCs, Neutrophils, Platelets, Memory B cells.

Answer 51

1: Neutrophils (shortest life-span). 2: Platelets. 3: RBCs. 4: Memory B cells (longest life-span).

Question 52

What are the names of the cells which detect reduced pO2?

Answer 52

Peritubular cells of the kidney.

Question 53

What is the name of the hormone which is released by peritubular cells of the kidney to promote maturation of erythrocyte precursors?

Answer 53

Erythropoietin (EPO).

Question 54

Where are erythrocyte precursors found?

Answer 54

Bone marrow.

Question 55

What is the name of the hormone which regulates platelet homeostasis?

Answer 55

Thrombopoietin.

Question 56

The hormone _______ stimulates ______ cells in the bone marrow to enlarge.

Answer 56

The hormone thrombopoietin stimulates megakaryocyte cells in the bone marrow to enlarge.

Question 57

Thrombopoietin is produced constitutively by the ______ and ______.

Answer 57

Thrombopoietin is produced constitutively by the kidney and liver.

Question 58

Match the circulating leukocyte to the differential count: Monocytes, Neutrophils, Lymphocytes, Basophils, Eosinophils.

Answer 58

Basophils: 0-0.75% of WBCs. Eosinophils: 1-3% of WBCs. Monocytes: 3-7% of WBCs. Lymphocytes: 25-33% of circulating WBCs. Neutrophils: 57-67% of WBCs.

Question 59

Which cell provides defence against HELMINTH infection?

Answer 59

Eosinophils.

Question 60

Which cell provides phagocytosis against bacteria in particular?

Answer 60

Neutrophils.

Question 61

Which cells provide adaptive immunity?

Answer 61

T and B lymphocytes.

Question 62

What component of blood is important for clotting?

Answer 62

Platelets.

Question 63

What cells are important for oxygen transport?

Answer 63

Red blood cells.

Question 64

Which cells are mildly phagocytosis APCs that differentiate into macrophages in tissues?

Answer 64

Monocytes.

Question 65

Which cells are important for allergic reactions?

Answer 65

Basophils.

Question 66

Order the following stages of neutrophil maturation, with the earliest being 1 and the latest being 6: Band cell, Myelocyte, Neutrophil, Myeloblast, Promyelocyte, Metamyelocyte.

Answer 66

Myeloblast (earliest). Promyelocyte. Myelocyte. Metamyelocyte. Band cell. Neutrophil (latest).

Question 67

Where are Langerhans cells found?

Answer 67

Epidermis.

Question 68

Where are sinusoidal macrophages found?

Answer 68

Spleen.

Question 69

Which lymphocyte kills 'stressed cells' in an MHC-independent fashion?

Answer 69

Natural killer (NK) cells.

Question 70

Which lymphocyte are 'lymphoid progenitor cells'?

Answer 70

Lymphoblasts

Question 71

Which lymphocyte produces immunoglobulins?

Answer 71

Plasma cells.

Question 72

Which lymphocyte suppresses immune functions?

Answer 72

CD4+ CD25+ (regulatory) T-cells.

Question 73

Which lymphocyte regulates immune functions e.g., in activating B cells?

Answer 73

CD4+ (helper) T-cells.

Question 74

Which lymphocyte kills virally-infected cells in an MHC-dependent fashion?

Answer 74

CD8+ cytotoxic T-cells.

Question 75

Identify the blood cells/components in the following high-power photomicrograph of a Giemsa-stained blood smear: A, B, C, D, E, F.

Answer 75

A: Eosinophil. B: Basophil. C: Neutrophil. D: Monocyte. E: Platelet. F: Lymphocyte.

Question 76

What stain is typically used when investigating WBC count in a bone marrow biopsy to assist in the diagnosis of a condition like chronic myeloid leukaemia (CML)?

Answer 76

Wright's stain.

Question 77

Which cell type would you NOT expect to see in a normal peripheral blood film? A) Band cells B) Lymphoblasts C) Reticulocytes D) Megakaryocytes E) Macrophages

Answer 77

A) Band cells.

Question 78

Where would the band cells visible in this blood film below normally be found?

Answer 78

In the bone marrow.

Question 79

From which site would bone marrow samples most likely be collected?

Answer 79

D) Superior iliac crest.

Question 80

By which method would a bone marrow sample most likely be collected?

Answer 80

Trephine biopsy.

Question 81

What class of drugs is used to treat Chronic Myeloid Leukaemia (CML)?

Answer 81

Tyrosine kinase inhibitors.

Question 82

Jaundice results from the deposition in the skin of which product of haemoglobin catabolism?

Answer 82

Bilirubin.

Question 83

What cells in the reticuloendothelial system is responsible for destroying damaged RBCs?

Answer 83

Macrophages.

Question 84

In which organ are platelets stored?

Answer 84

Spleen.

Question 85

Which tissue-resident immune cell shares many features with basophils?

Answer 85

Mast cells.

Question 86

Which T-cell population is depleted in HIV infection?

Answer 86

Helper-T cells (CD4+).

Question 87

Which immune structure monitors blood, as opposed to lymph, for infectious agents?

Answer 87

Spleen.

Question 88

Which tissue-resident immune cell shares many features with basophils?

Answer 88

Mast cells

Question 89

Which T-cell population is depleted in HIV infection?

Answer 89

Helper-T cells (CD4+)

Question 90

Which immune structure monitors blood for infectious agents?

Answer 90

Spleen

Question 91

In which bone does relatively LITTLE haematopoiesis take place in adults?

Answer 91

Femur

Question 92

Which interleukin is primarily involved in the development of myeloid lineages?

Answer 92

IL-3

Question 93

Which metabolic process does NOT occur in RBCs?

Answer 93

TCA cycle