Intro to haematopoietic system_ part 1.pdf

19/10/23 Intro to the haematopoietic system: part 1 Embryonic stem cell differentiation: Blood and the vessels that carry/ process blood all derive from haemangioblast cells. Blood formation in the developing embryo: initial blood source Blood formation occurs in the yolk sac originally but this is...

19/10/23 Intro to the haematopoietic system: part 1 Embryonic stem cell differentiation: Blood and the vessels that carry/ process blood all derive from haemangioblast cells. Blood formation in the developing embryo: initial blood source Blood formation occurs in the yolk sac originally but this is then supplanted by the liver. During the last 2 to 3 months of development, the bone marrow takes over as the most important source of blood. Haematopoiesis in an adult: Haematopoiesis is blood production. Baus progenitor d Pryogeaning ti our lymphoid Natura killer I h megakaryoblasts myeloid herythroblasts The haematopoietic stem cells are very rare and slow growing. They maintain a state of dormancy and divide once every 20 weeks. These cells are pluripotent which means they can give rise to all the different types of blood cells. They also have the ability to self renew but this is limited by the number of times they can divide ( hay ick limit ). Haematopoietic stem cells can differentiate into haematopoietic progenitor cells and these progenitor cells are much more numerous and proliferative. From these progenitor cells, we get t wo main streams of blood cell development. They will either follow a myeloid or lymphoid lineage. So myeloid cells will come from the common myeloid progenitor cell and the same for lymphoid. These cells can’t self renew. Bone marrow in uences differentiation: I Hypoxic Bet ween the t wo niches there are cells whose responsibility it is to provide matrix and growth factors to facilitate survival, proliferation and differentiation of cells involved in Haematopoiesis. Some examples of these major niche components include collagen and glycoproteins ( bronectin and thrombospondin ) and glycosaminoglycans such as hyaluronic acid and chondroitin derivatives. These provide a support matrix for the cells to grow on and growth factors and cell-cell interactions from support cells such as osteoblasts, mesenchymal stem cells and broblasts then provide these cells with cytokines and growth factors to allow them to either be maintained in a particular state of differentiation or promote differentiation into the various blood cell types. There are stromal cells in the bone marrow which are a major source of growth factors. Oxygen also plays an important part within the osteoblastic niche, oxygen struggles to enter into the osteoblastic niche causing a hypoxic environment. This keeps haematopoietic stem cells more or less quiescent ( inactive ), whereas oxygen levels are increasing as cells enter the vascular niche and eventually into circulation which prompts rapid growth of differentiated cells. Role of growth factors and cytokines: Epigenetic control of gene transcription: Gene transcription can only occur if the chromatin structure is relaxed from a condensed state ( heterochromatin ) to a more open stage ( euchromatin ). Different types of blood cells: d blood whitecus granulocytes s agranuloastes Red blood cells ( erythrocytes ): Anucleate cell whose function is to carry oxygen from the lungs and return carbon dioxide. Blood groups: The blood types are de ned by the expression of an ABO gene. This gene codes for an enzyme that modi es the addition of different carbohydrate residues to glycoproteins and glycolipids on the surface of the red blood cell. People who express antigen A have red blood cells that bear the n-acetyl galactosamine residues on the surface. People who have the B antigen express galactose residues and people with antigen O don’t express a functional enzyme and therefore these glycoproteins and glycolipids bear the H antigen which only contains a fucosyl group. An individual will create antibodies to whichever antigens they don’t express. This is shown in the diagram. Rhesus positive or negative depending if the rhesus gene is expressed. Platelets/ thrombocytes Main function is to clot the blood following injury. Initiates wound healing. Neutrophils: These are short lived, motile cells designed to phagocytose bacteria and combat tissue infection. They squeeze between endothelial cells have a multi-lobed nucleus which allows extreme deformability. Neutrophils engulf bacteria to form a phagocytic vacuole. The cytoplasmic granules fuse with the vacuole to deliver bactericidal products. Eosinophils: Host defence against parasitic infections. Secretes lysozymes, ROS and toxic proteins to kill parasite, and leukotrienes and prostaglandins to mediate in ammation. Basophils: Are the only circulating leukocytes that contain histamine. Tissue resident counterpart - mast cell. Activated by PAMPS and antigen cross linking of FeeRI receptor-bound IgE to undergo rapid degranulation and release their cellular contents. Monocytes/ macrophages: Monocytes are maturing cells on their way from bone marrow to tissues where they form macrophages. Macrophages function as long-lived tissue phagocytes associated with chronic in ammation and infection. T-cells: These are much more long lived than eosinophils and neutrophils. T cells start as naive T cells and then will differentiate either into what we call helper T cells or a cytotoxic T cell. Pro-T cells migrate from bone marrow to thymus where they further differentiate into CD4+ and CD8+ cells. T lymphocytes that cannot bind MHCs or that bind self-MHC/self- peptide too tightly undergo apoptosis. Basically as they pass through the thymus, the are educated on what antigens are normally in your tissues, any cells that try to imitate a response to your normal antigens are killed so they when the T cells leave the thymus they only imitate a response to non self antigens. B-cells: Naive B cells enter the blood and transit through the spleen and lymph nodes tissue to encounter antigen. Differentiate into Memory B cells Plasma cells ( produce antibodies ) Natural killer cells: Initiate lymphoid cells Kill virally-infected cells through direct induction of lysis