7. Stem Cells and Blood Flashcards
Name the 8 cells produced from Haematopoietic stem cells.
Eosinophils, RBCs, Megakaryocytes, Basophils, Neutrophils, Macrophages, Thymocytes and B Cells
Name the two components of the immune system.
Humoral Immunity and Cellular Immunity.
Name the two types of immune response.
Innate (natural) and Adaptive (acquired)
What is the role of Cytokines?
Low molecular weight, secreted protein that stimulates or inhibits cell differentiation and proliferation
What are antibodies?
Multi-chain glycoproteins that are produced by B-lymphocytes and which contain a very variable antigen-binding site and a functional (or constant) region.
Name the 3 types of Lymphocytes
T cells, B Cells and NK Cells (latter dont need to learn)
Name the 3 types of phagocyte
Monocytes, Macrophages and Neutrophils
Name the 3 types of Granulocytes
Eosinophils, Basophils and Mast Cells
Which cells produced by haematopoietic stem cells, are not considered to be part of the immune system?
RBCs and Platelets
Which cells are produced from myeloid stem cells?
Eosinphils, RBCs,Megakaryocytes, Basophils, Neutrophils and Macrophages
Which cells are produced from lymphoid stem cells?
Thymocytes and B Cells
What creates the specificity of the immune responses?
Lymphocytes, Small nucleated leukocytes
Where do T cells mature?
Thymus
List the four reasons why T cells are important.
Enhancing B cell responses, Enhancing phagocyte killing of intracellular bacteria, Killing virally infected cells and Regulating adaptive immunity.
Name a disease that can be caused due to lack of T cells.
DiGeorge Syndrome - Thymus doesn’t develop, immunoglobulin levels disturbed Leads to Candidaiasis, Pneumonia and diarrhea
Which cells produce antibodies (immunoglobulin)?
Plasma B cells
Where are B cells produced and mature?
Bone Marrow
What is the function of B cells?
They and their products are central to attacking extracellular pathogens (bacteria)
Name a disease that can be caused due to lack of B cells.
X-linked infantile hypogammaglobulinaemia - inability to produce any immunoglobulin - recurrent bacteria infection.
What is the difference between innate and adaptive immunity?
Adaptive Immunity: Shows learning, memory, specific antigen receptors (property of T and B Cells)
Innate Immunity: No learning or memory, Pattern Recognition receptors (Property of NK cells, Macrophages, Neutrophils and Complement)
What is the function of the protein complement?
Soluble proteins that complement the action of the antibodies, can also kill pathogen directly and mainly produced by liver
Describe the structure of Neutrophils.
Have a single, multi-lobed nucleus. Fine blue granules contain proteases and anti-microbial effector molecules such as defensins
Which molecule shows chemotaxis and what does it mean?
Neutrophils show chemotaxis and they are attracted to bacterial chemical products like the peptide fMLP
What is the function of eosinophils?
Mainly responsible for killing parasites that cannot be digested and they bind to antibody coated parasites, degranulate and dissolve the cell surface.
What is the function of basophils and mast cells?
They are involved in the acute inflammatory response and important in allergy and hypersensitivity.
What is the main difference between basophils and mast cells?
Basophils are circulatory and mast cells inhabit the mucosa and connective tissue.
Name the 5 Haematopoietic progenitors that you need to learn.
Haematopoietic stem cells (HSC), Multi-potent Progentor (MPP), Common Lymphoid progenitor (CLP), Granulocyte/monocyte progenitor (GMP) and Megakaryocyte/Erythroid Progenitor (MkEP)
Describe Early Erythropoietic Differentiation.
Pluripotential Stem Cells to Multipotential Stem Cells to BFU-E to CFU-E to Proerythroblasts which give rise to 16 erythrocytes
What does “-blast” at the end of a word indicate?
Indicates nucleus is still present.
What does “normo-“ at the start of a word equal to?
“Erythro-“ at the start
How many cell divisions do proerythroblasts normally undergo?
4
List the late erythropoietic changes
Cell volume gets smaller, nucleus gets more smaller and more dense, ejected in progression to reticulocyte and more and more haemoglobin present.
Describe the structure of Proerythroblast.
Large (12-14 micrometres), Prominent nucleus and one or more nucleoli.
Describe the structure of Basophilic Erythroblasts.
High Affinity for methylene blue, Similar in size or slightly smaller, nucleus still relatively large and no nucleoli
Describe the structure of Polychromic Erythroblast.
Size is about 10 micrometres, nucelus much reduced and cytoplasm much paler and pink hues.
Describe the structure of Orthochromic Erthroblast.
Nucleus even smaller, denser staining, and spherical. Cytoplasm even more pink.
Describe the structure of Reticulocyte.
No nucleus, methylene blue stains a network of strands in cytoplasm (RNA), Lightly larger than erythrocyte.
Name the molecules involved in control of erythropoiesis.
Cytokines, SCF, IL3, Thrombopoietin and Erythropoietin (epo)
What causes increased Epo production?
Anaemia - leads to more mRNA in kidney and liver.
When are Epo expressed?
Low levels of expression at BFU-E and high level expression at CFU-E and Epo is very sensitive to proerythroblast
What is the role of Epo in erythropoiesis?
Promotes differentiation of megakaryocytes
What happens during primary haemostasis?
Reduction of blood flow, Formation of a temporary plug in wall of damaged blood vessel. This is due to interaction of platelets and blood vessels
What happens during secondary haemostasis?
Conversion of soluble fibrinogen to insoluble fibrin, strengthens initial haemostatic plug and this is due to soluble plasma proteins
What happens during Fibrinolysis?
Degradation of fibrin plug after repair of wound.
What are platelets?
Small membrane bound packets of granular cytoplasm with no nucleus.
How are platelets produced?
They are during Thrombopoiesis in which they are formed by the pinching off and shedding of megakaryocytes
What is the importance of Thrombopoietin?
Stimulation of megakaryocyte differentiation and proliferation. they are produced by kidney and liver.
What are the 3 distinct processes occurring in thrombopoiesis?
Proliferation, Maturation and Circulation
How long is the process of Thrombopoiesis
4-15 days
What does endomitosis mean?
Nuclei undergo multiple mitotic divisions but no cytoplasmic division - formation of connected lobes.
What happens during Proliferation?
Megakaryocytic cells undergo endomitosis. Process takes about 4 days in total. Produces very large cytoplasmic volume from which platelets bud.
What happens during Maturation?
Formation of Secretory granules and demarcation membrane system which produces large surface area of membrane required for platelet shedding. Takes place between days 3-5.
What happens during circulation?
Release of proplatelet packages, large cytoplasmic fragments undergo further fragmentation to form individual platelets. End with phagocytosis of nuclei and remaining cytoplasm. Occurs over day 4-15
What is maturation and platelet release regulated by?
Thrombopoietin.
How many platelets per day are produced by a single megakaryocyte?
40-60 platelets (about 1.6 x 10^11 platelets produced per day)
How many days can platelets survive in circulation?
9-12 days
How are old damaged and effete platelets removed?
Removed by sequestration in the spleen, followed by phagocytosis.
What is the role of Canallcull in the structure of Platelets?
Channels deep into interior which radically increases surface area.
What is the role of Glycocalyx - Surface Coat?
Contains glycoproteins that have a role in adhesion and aggregation and receptors for coagulation factors which enhance coagulation.
What can you find on the plasma membrane of a platelet?
ADP receptor and platelet factor VIII
What do the platelet granules contain and what are their roles?
Calcium, magnesium, ADP/ATP (for platelet aggregation), Serotonin and Thromoxane (for vasoconstriction) and PDGF (Platelet derived growth factor)
What are the two phases of primary haemostasis?
Vascular and Platelet Phase
Why does blood vasoconstriction occurs?
Restricts blood flow to area after injury. Neurogenic Response.
What do the platelet adhere to?
Collagen exposed after injury breaks endothelial lining.
What further exposes the basement membrane and collagen?
Contraction - Further platelet recruitment
What causes release of vasoconstrictors (thromboxane and 5-HT)
Activation of Platelets
What does prostacyclin do?
Inhibits platelet aggregation and causes vasodilation when theres no injury.
What does the production of vWF cause?
Synthesis of basement membrane (damage repair)
Describe the role of Thromboxane and Prostacyclin.
Thromboxane: Supresses cAMP sythesis which elevates Ca2+ levels.
Prostacyclin: Activates cAMPsynthesis which reduces Ca2+ levels.
What does nitric oxide cause?
It inhibits platelet activation and promotes vasodilation by raising cGMP levels
What molecules act as a bridge between the platelet and membrane resulting in platelet adhesion?
vWF and Factor VIII
What effect does adhesion of platelets have on the platelets themselves.
Changes from discoid to irregular shape with pseudopod like projections which adhere to other platelets
What causes granule release from platelets?
Activation of receptors for ADp, thromboxane and thrombin.
What is the role of ADP and thromboxane?
Act as platelet chemoattractants
