Lecture 3.2: Blood Cells and Haematopoiesis

Question 1

What is Haematopoiesis?

Answer 1

It is the process of producing mature blood cells from precursor cells

Question 2

Sites of Haematopoiesis

Answer 2

Foetal blood cells form initially in the yolk sac

From 2nd trimester, haematopoiesis takes places primarily in the liver

From 3rd trimester, in the bone

In adults, blood cell formation takes places in the red marrow of the sternum, pelvis, vertebrae, ribs and skull

Question 3

Mature blood cell development

Answer 3

Hormones regulate mature blood cell development from progenitors

Question 4

Erythrocytes (RBCs)

Answer 4

Anucleate cells, densely filled with haemoglobin

Flexible, biconcave discs

Large surface area for gas exchange

Deliver O2 to tissues, and return CO2 to lungs

Lack of mitochondria necessitates glycolysis to be their main source of ATP

Question 5

Control of Erythropoiesis

Answer 5

Reduced ppO2 is detected by the interstitial peritubular cells of the kidney, stimulating them to produce erythropoietin (EPO)

EPO stimulates maturation of nucleated precursors (erythroblasts) in the bone
marrow, and release of mature RBCs into the circulation

A rise in RBCs is accompanied by a rise in pO2, and EPO production falls

Question 6

Haemoglobin Deficiencies: Anaemia

Answer 6

Blood loss

Decreased RBC production

Reduced haemoglobin/increased RBC destruction: Thalassemia: inherited
mutations in α- and βhaemoglobin chains, Sickle-cell anaemia

Question 7

Removal of damaged RBCs: where? what is system made of? what is removed/resorbed?

Answer 7

Removed by the reticuloendothelial system (RES)

The RES (mononuclear phagocyte system) is comprised of the monocytes and macrophages of the lymph nodes, spleen and liver (Kupffer cells)

Macromolecules and iron are recovered from haemoglobin, and waste is excreted

The spleen is the only lymphoid organ that surveills the blood, is a site of Ab production & lymphocyte activation, also provides a reservoir for platelets.

Question 8

Haemoglobin Catabolism (Step 1-5)

Answer 8

1) Haemoglobin is separated into heme and globin in the RES

2) Iron is recovered from heme and transferred to the bone marrow, leaving biliverdin

3) Biliverdin is reduced to bilirubin, transferred to the liver, it forms a component of bile

4) Bilirubin is converted to urobilinogen in the colon by the action of gut commensal bacteria

5) Is excreted in faeces as stercobilin (brown compound), or from the urine as urobilin (straw coloured)

Question 9

Platelets

Answer 9

Anucleate 2-3 µm cell fragments

Derived from bone marrow megakaryocyte

They contain a range of factors critical for blood clotting and vessel wall repair.

Question 10

Control of Platelet Numbers

Answer 10

Thrombopoiesis is controlled by hormone thrombopoietin (TPO), which is
produced by the liver and kidneys

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, whereupon it is destroyed, reducing the bioavailability of the hormone as platelet numbers rise

Question 11

Innate Immunity

Answer 11

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

Question 12

Innate Immunity: Neutrophils

Answer 12

Neutrophils are the most common circulating leukocyte (40-75% WBC), lifespan of 1-4 days

Lobed nuclei (polymorphonuclear cells)

Recruited to sites of infection to phagocytose invaders

Granules contain proteases, antibacterial peptides and oxidising agents

Question 13

Adaptive Immunity

Answer 13

The adaptive immune response is specific to the pathogen presented

So it is fairly slow

Question 14

Humoral Immunity

Answer 14

Involve the secretion of immunoglobulins (antibodies) by B cells

Question 15

Cell-Mediated Immunity

Answer 15

Involving the killing of infected (self) cells by T cells

Question 16

Eosinophils

Answer 16

Account for 1-6% of circulating leukocytes, lifespan of 6-9 days

Characteristic red granules are revealed by Wright’s stain

Abundant in connective tissue of intestinal lining, and in lungs of asthma patients

Functions include combating helminth infections, mediating hypersensitivity reactions and phagocytosing antigen-antibody complexes

Question 17

Basophils

Answer 17

Half-life 2.5 days, least-common WBC, 0.2-1% of circulating leukocytes

The purple-staining (basophilic) granules within their cytoplasm contain histamine, heparin and pro-inflammatory factors

Important in type 1 hypersensitivity reactions

Question 18

Monocytes

Answer 18

Account for 2-10% of total WBC count, varied lifespan (days)

Are ‘agranulocytes’ that leave the circulatory system by diapedesis, and mature into macrophages in tissues

Large kidney-shaped nucleus

Respond to inflammation, and act as antigen-presenting cells

Fine cytoplasmic granules contain lysosomes.

Phagocytic and pinocytic

Question 19

Macrophages

Answer 19

Can have a lifespan of several years

Derived from circulating monocytes

Phagocytic, degrading foreign organisms and cell debris

‘Professional antigen presenting cells’: able to present foreign material to T-lymphocytes

Question 20

Natural Killer (NK) Cells

Answer 20

NK cells are a class of lymphocytes that produce a rapid response to viral infection, and are an important component of innate immunity

NK cells also recognise “stressed” cells such as tumour cells

Mechanism of killing similar to cytotoxic T cells, albeit with less specificity

Question 21

Lymphocytes

Answer 21

Lymphocytes constitute 20-50% of circulating leukocytes

Memory B cells can live for many years

Appear spherical in histological preparations, with a thin strip of cytoplasm surrounding a large, but regularly-shaped nucleus

In both B and T lymphocytes, genomic DNA undergoes somatic rearrangements to create a vast repertoire of immunuoglobulins and T cell receptors

Question 22

B Lymphocytes

Answer 22

B lymphocytes “shuffle” the DNA encoding their immunoglobulins, to create a repertoire of antibodies able to recognise a variety of antigens

If a B cell is presented to a foreign antigen that it recognises, it will proliferate (under the control of T helper cells)

They form a population of plasma cells that will produce antibodies specific for that antigen

Long-lived memory B lymphocytes are able to expand again following re-exposure to an antigen

Question 23

T Lymphocytes

Answer 23

Originate in the bone marrow, but mature in the thymus (or spleen in adults) and undergo rearrangement of their T cell receptor genes

CD4+ (T helper) cells induce proliferation and differentiation of T and B cells, and activate macrophages

CD8+ (T cytotoxic) cells induce apoptosis in virally-infected cells by punching holes in the plasma membrane with perforin and injecting granzymes

Question 24

Mast Cells

Answer 24

Resident in connective tissue

Are components of the innate immune system, but also play a role in allergy

Their granules contain: heparin (an anticoagulant), histamine (increases blood vessel wall permeability), cytokines to attract eosinophils and neutrophils

Question 25

Mast Cells and Hypersensitivity

Answer 25

Type I hypersensitivity is pathological response resulting from mast cell hypersensitivity to stimulation by allergens

Responses can be localised (as in allergy) or systemic (as in anaphylaxis)

Following an 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 26

Anaemia resulting from loss of globin chains through mutation

Answer 26

Thalassemia

Question 27

Any type of anaemia in which RBCs are smaller than normal
Often caused by iron deficiency

Answer 27

Microcytic Anaemia

Question 28

A type of anaemia in which RBCs are of normal size

Answer 28

Normocytic Anaemia

Question 29

Defects in spectrin leads to the formation of elliptical cells

Answer 29

Hereditary Elliptocytosis

Question 30

RBCs round up due to loss of cytoskeletal-associated proteins such as spectrin

Answer 30

Hereditary Spherocytosis

Question 31

Any type of anaemia in which RBCs are larger than normal
Can be caused by vitamin B12 and folate deficiency

Answer 31

Macrocytic Anaemia

Question 32

RBC membranes become fragile due to cycles of polymerisation of haemoglobin

Answer 32

Sickle Cell Anaemia