Lecture 3.2: Blood Cells and Haematopoiesis Flashcards
What is Haematopoiesis?
It is the process of producing mature blood cells from precursor cells
Sites of Haematopoiesis
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
Mature blood cell development
Hormones regulate mature blood cell development from progenitors
Erythrocytes (RBCs)
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
Control of Erythropoiesis
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
Haemoglobin Deficiencies: Anaemia
Blood loss
Decreased RBC production
Reduced haemoglobin/increased RBC destruction: Thalassemia: inherited
mutations in α- and βhaemoglobin chains, Sickle-cell anaemia
Removal of damaged RBCs: where? what is system made of? what is removed/resorbed?
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.
Haemoglobin Catabolism (Step 1-5)
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)
Platelets
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.
Control of Platelet Numbers
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
Innate Immunity
An immediate, yet relatively non-specific and transient response to infection
Innate Immunity: Neutrophils
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
Adaptive Immunity
The adaptive immune response is specific to the pathogen presented
So it is fairly slow
Humoral Immunity
Involve the secretion of immunoglobulins (antibodies) by B cells
Cell-Mediated Immunity
Involving the killing of infected (self) cells by T cells
Eosinophils
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
Basophils
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
Monocytes
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
Macrophages
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
Natural Killer (NK) Cells
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
Lymphocytes
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
B Lymphocytes
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
T Lymphocytes
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
Mast Cells
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
Mast Cells and Hypersensitivity
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
Anaemia resulting from loss of globin chains through mutation
Thalassemia
Any type of anaemia in which RBCs are smaller than normal
Often caused by iron deficiency
Microcytic Anaemia
A type of anaemia in which RBCs are of normal size
Normocytic Anaemia
Defects in spectrin leads to the formation of elliptical cells
Hereditary Elliptocytosis
RBCs round up due to loss of cytoskeletal-associated proteins such as spectrin
Hereditary Spherocytosis
Any type of anaemia in which RBCs are larger than normal
Can be caused by vitamin B12 and folate deficiency
Macrocytic Anaemia
RBC membranes become fragile due to cycles of polymerisation of haemoglobin
Sickle Cell Anaemia
