5.1. Hematopoiesis. The composition of the blood. The human blood group systems. Flashcards

Question

4. HEMATOPOIESIS A f/ 2 examples of Stress-induced hematopoiesis

Answer 1

1/ Hypoxia will lead to increased production of RBCs 2/ Infection will lead to increased production of granulocytes (WBC)

Answer 2

The bone marrow contains yellow and red bone marrow

Answer 3

Yellow bone marrow contain inactive, mainly fat cells

Answer 4

Red bone marrow contains actively producing RBCs - Also contains hematopoietic cells, stromal cells and hematopoietic stem cells (HSC) - Stromal cells serve as structural support, signaling and control of hematopoietic cell maturation

Answer 5

HSCs cells are cells in which all the cells of the circulating blood are derived from

Answer 6

1/ Uncommitted 2/ Asymmetric division 3/ Self-renewal capacity 4/ Pluri/multipotency (able to differentiate other cells) 5/ Don’t have specific morphology (cell surface markers)

Answer 7

the determination of mature cells or stem cells which can be used to measure or count different types of cells

Answer 8

1/ CD34+ = (CD = cluster of differentiation) - A cell migration/adhesion regulator that may help stem cells bind to marrow matrix 2/ C-kit is a receptor tyrosine kinase which binds “stem cell factor”

Answer 9

You can find evidence of hematopoietic stem cells in bone marrow

Answer 10

1/ LT – HSC (long term) - Pluripotent 2/ ST – HSC (short term) - Multipotent 3/ MPP (Multipotent progenitor)

Answer 11

1/ Mainly in red bone marrow 2/ Peripheral blood (chord blood)

Answer 12

It is a stem cell that can develop into many different types of cells or tissues in the body - Embryonic stem cells are considered as pluripotent

Answer 13

- Multipotent cell is a stem cell that can differentiate into particular cells types associated with multiple cell lineages (more limited than pluripotent) -> Adult stem cells are considered as multipotent

Answer 14

1/ Hematopoiesis begins with HSCs and then steadily differentiate 2/ HSCs (LT-HSCs and ST-HSCs) first become MPP (multipotent progenitor cells 3/ MPP cannot self-renew, but their daughter cells will differentiate into 2 types of oligopotent progenitors which are CMP (common myeloid progenitor) and CLP (common lymphoid progenitor) - CMP can differentiate into MEP (megakaryocytic erythroid progenitors) and GMP (granulocyte monocyte progenitor) 4/ Oligopotent progenitors will then differentiate into unipotent progenitors 5/ Unipotent progenitors will differentiate into differentiated cells

Answer 15

1/ T-cell progenitor will differentiate and complete their development into T-cells in thymus 2/ Note for the diagram Green: pluri/multipotent cells Blue: oligopotent Red: unipotent Black: differentiated/ specific cells

Answer 16

1/ Local humoral factors - From developing blood cells, stromal cells - E.g, cytokines, Hematopoietic growth factors (GFs) 2/ Local cell-cell interactions - Bone marrow “niche” 3/ General humoral factors - From blood steam - E.g, hormone, cytokines, Hematopoietic growth factors (GFs)

Answer 17

1/ There are many regulatory factors with overlapping effects 2/ Regulatory factors involved: - IL-3 (solute) (Interleukin 3) - GMCSF (solute) (Granulocyte-macrophage colony-stimulating factor) - CSF +) Solute + cell surface +) Receptor: C-kit

Answer 18

1/ There is few or 1 regulatory factors with no overlapping effects 2/ Examples of regulatory factors - EPO (Erythropoietin) - G– CSF (Granulocyte colony-stimulating factor (G-CSF)) - M – CSF - Thrombopoietin (TPO) - IL – 7 (lymphoid)

Answer 19

1/ The environment of the cell (cell-to-cell connections) is important in the differentiation of blood cells in the bone marrow 2/ Cells will take on certain differentiation routes (an area dedicated to a certain function like this = niche), therefore chemokines exist in the bone marrow to induce cell movement to different parts in the bone marrow (via chemotaxis) 3/ Niche = area in which stem cells are present in (1) an undifferentiated state and (2) a self-renewable state - Divisional asymmetry: only a certain type divide, hence limited number of production - Environmental asymmetry: some niches produce a certain type of cells more than the others

Answer 20

1/ Definition: Glycoproteins (EC signal protein) which affects cells 2/ Their function is usually overlapping and can work for several cells (mast cells, B-cells, stem cells, etc.) 3/ Acts as local mediator in cell-cell communication (induce movement, vision)

Answer 21

1/ Erythropoietin (EPO) - Secreted by kidney in response to cellular hypoxia 2/ Granulocyte-colony stimulating factor (G-CSF) which stimulate WBCs production

Answer 22

Stimulating committed progenitor to proliferate in vitro

Answer 23

E.g, M-CSF, G-CSF -> Form colony of specific lineages -> Form CFU (colony-forming unit) -> E.g, CFU – GEMM, CFU – E

Answer 24

Definition: erythropoiesis the the development from erythropoietic stem cell to mature RBCs

Answer 25

Definition: erythropoiesis the the development from erythropoietic stem cell to mature RBCs

Answer 26

1/ 7 to 10 days RBC production process occurs in erythropoietic islands 2/ Form from the myeloid lineage -> proerythroblasts-> erythroblasts 3/ Slowly gain more hemoglobin and their nuclei shrink -> orthochromatic erythroblasts 4/ A macrophage absorbs the nucleus of the erythroblast and then becomes reticulocyte, which is anuclear and also without mitochondria

Answer 27

BM erythroblastic islands (IBM) which are embedded in EBI macrophages *Note: - Erythroblastic islands (EBIs)

Answer 28

1/ Control of erythropoiesis – the erythropoietin 2/ ON-OFF regulation of EPO synthesis in renal EPO producing (REP) cells 3/ O2 sensing mechanism

Answer 29

1/ Erythrocyte production is regulated by erythropoietin (EPO), which is mainly produced in the kidney by interstitial fibroblasts (90%). 2/ Erythropoietin (EPO) can also be produced by hepatocytes in liver (10%)

Answer 30

Definition: Production of EPO is a negative feedback mechanism that is regulated by O2- concentration in the kidney

Answer 31

- Hypoxia: Low O2 content in kidneys causes hypoxia-inducible factor (HIF) to activate, causing production of EPO which leads to increased erythrocytes and then increased O2-content of kidney - This will lead to normoxia which in turn inhibit the synthesis of EPO

Answer 32

1/ HIF-⍺ is a transcription factor that regulates the expression of EPO 2/ At the normal level, HIF-⍺ levels are low, where as HIF-⍺ levels increases in hypoxia

Answer 33

1/ O2 activates proxyl hydrolyase which will then hydroxylate HIF-⍺ 2/ This hydroxylation stimulates the interaction of HIF-⍺ with VHL (Von Hippel-Lindau disease tumor surpressor protein), leading to ubiquination by Ubiquitin ligase 3/ Leads to degradation of HIF-⍺ (by proteasomal degradation)

Answer 34

1/ proxyl hydrolyase are inactivated 2/ HIF-⍺ accumulates in nucleus and then interacts with hypoxia response element and form a complex with HIF-β 3/ EPO gene expression increases abnormally

Answer 35

1/ Amino acids 2/ Vitamin B6 3/ Iron 4/ Vitamin B12 5/ Folic acid

Answer 36

Deficiency in dietary requirements for normal erythropoiesis

Answer 37

1/ Normocytic 2/ Microcytic 3/ Macrocytic

Answer 38

4.5 – 5 million/µl

Answer 39

0.42 – 0.46

Answer 40

2.2 – 2.5 mM (tetramer)

Answer 41

0.5 fmol/ cell (Note: fmol mean femtomole (1fmol = 10-15 moles))

Answer 42

Thrombopoiesis is the formation of platelets in blood

Answer 43

Formed from the myeloid erythrocyte progenitor -> promegakaryoblast -> Promegakaryocyte -> megakaryocyte -> immigration towards the BM sinusoids -> shedding of platelets

Answer 44

1/ Undergo endoreduplication (replication of genome in absence of mitosis) (32n) 2/ Extremely large diameter (60μm), hold lots of duplicated DNA 3/ Lobulated nucleus 4/ Their processes extend into blood vessels and disintegrate to become ~104 platelets

Answer 45

- By using TPO (thrombopoietin) which is produced mainly in the liver (+ kidney) - Thrombopoietin receptor is c-mpl on megakaryocytes and platelets 1/ If the number of platelets increases, TPO level will decreases 2/ If the number of platelets decreases, TPO level will increases -> It will then bind to receptors and cause platelet production (only with megakaryocytes) along with TPO degradation (for balance)

Answer 46

1/ They all develop from GMP (granulocyte-monocyte progenitors) 2/ Monoblasts can form either osteoclasts, macrophages or dendritic cells (6 days) 3/ Granulocytes take 9 to 12 days to mature, but can be sped up to 2 days in cases of infection (thanks to cytokines) 4/ Mature granulocytes exit the bone marrow and either freely circulate or they attach to the endothelial cells of blood vessels

Answer 47

1/ They have genetically determined antigens (Ag) on the surface 2/ Glycoproteins, glycolipids and integral membrane proteins 3/ There are about 30 blood group system 4/ There are about 300 antigens

Answer 48

1/ Antigen is composed of glycosphingolipids 2/ Codominant inheritance 3/ Ag gene codes for monosaccharide transferase enzymes

Answer 49

1/ H-gene -> fucosyltransferase => H-antigen => Core structure 2/ O – gene -> inactive enzyme => H-antigen 3/ A-gene -> GalNac transferase => A-antigen 4/ B-gene -> Gal transferase => B-antigen

Answer 50

1/ Type O: neither A nor B antigens are present. - O is recessive 2/ Type A: only type A antigen is present 3/ Type B: only type B antigen is present 4/ Type AB: both A and B antigens are present - Co-dominance

Answer 51

1/ Characteristics: IgM type immunoglobulins (5 x 2 binding sites for antigens) 2/ Role: - They are present in the blood - Naturally against non-self ABO antigens

Answer 52

- If an antigen is present on RBCs of an individual, the corresponding antibody must be absent in the plasma. (Self-tolerance) - If an antigen is absent on RBCs of an individual, the corresponding antibody must be present in the plasma.

Answer 53

1/ If an antigen is present on RBCs of an individual, the corresponding antibody present => There will be agglutination 2/ If an antigen is absent on RBCs of an individual, the corresponding antibody is absent => There will be no reaction

Answer 54

1/ There are 6 common types of Rh antigens, but the type D antigen is widely prevalent and more antigenic than other Rh antigens. 2/ Anyone who has the type D antigen is said to be Rh positive, and a person without it is Rh negative.

Answer 55

1/ When the mother is Rh – and the father is Rh +, the baby inherits Rh+. 2/ The mother develops anti-Rh antibodies from exposure to the fetus’s Rh antigen. 3/ Then, the mother’s antibodies diffuse through the placenta into the fetus and cause RBC agglutination. 4/ The incidence rises progressively with subsequent pregnancies.

Answer 56

1/ Acute (IgM-mediated) 2/ Delayed (IgG-mediated)

Answer 57

Complement activation - Hemolysis - Proinflammatory mediator release - Disseminated intravascular coagulation

Answer 58

Incomplete complement activation - Splenic & hepatic erythrophagocytosis - Anemia - Jaundice