Introduction to Haematopoiesis I Flashcards
Components of blood
Plasma (55%) - >95% of water, 6-8% dissolved proteins, glucose, electrolytes, hormones and CO2
White blood cells and platelets (< 1%)
Red blood cells (45%) - 93-96% erythrocytes, 4-7% platelets, 0.1-0.2% leukocytes.
Functions of blood
Functions to transport glucose, electrolytes and gases
Involved in regulation of homeostasis
Involved in immune response
Other name of red blood cells
Red blood cells are called erythrocytes.
Haematocrit
The proportion of the total blood volume occupied by red blood cells is called the haematocrit.
The proportion of the total blood volume occupied by red blood cells is called?
Haematocrit
What do erythrocytes lack?
Important to note that mature mammalian erythrocytes lack a nucleus as the nucleus is ejected as red blood cells are formed from the bone marrow.
What is haemoglobin?
Red blood cells of vertebrae contain haemoglobin which is a protein that transports oxygen around the body.
Other name of white blood cells
Leukocytes
Structure of white blood cells
Larger than erythrocytes and do have a nucleus
What are the two types of white blood cells?
Granular and Agranular
Granular leukocytes
The granular leukocytes comprise the neutrophils, eosinophils and basophils. These are cells of the innate immune system that are involved in hunting down the pathogen.
Agranular leukocytes
Agranular leukocytes are the monocytes and the lymphocytes and these cells are involved in the immune response and the control of infection.
What do all blood and vessels that carry/process blood derive from?
Haemangioblast cells
How are haemangioblasts formed
Starts during embryogenesis.
Starts with development of blastocysts (pluripotent stem cells) that undergo self-renewal and divide into various tissue layers: ectoderm, mesoderm and endoderm.
Within mesoderm, you get the formation of precursor cells called haemangioblasts and these are then able to form vascular tissue or the blood cells themselves.
How does blood cell formation occur?
Blood cell formation begins on the yolk sac where a form of primitive haemopoiesis leads to erythrocyte precursor cells and formation of blood islands that are necessary to supply erythrocytes to the developing foetus. This type of haematopoiesis is transient. With the formation of the aorta-gonad-mesonephros comes the appearance of haemangioblast cells which are the precursor for endothelial and haematopoietic cells and haemangioblast cells are then believed to seed the liver and bone marrow for haemopoiesis to take place.
Active Sites of Blood Formation (Haematopoiesis)
Blood production practically takes place in all marrow of the bone during infancy but this is gradually reduced, being replaced by fatty tissue as the infant grows. And eventually, blood production only takes place in the bones of the central skeleton and the proximal ends of the femurs and humeri.
How does haematopoiesis start?
Haematopoiesis starts with haematopoietic stem cells and these are rare. Perhaps only one in every 20 million nucleated cells in the bone marrow. They are very slow growing and maintain a state of dormancy dividing perhaps once every 20 weeks. These cells are pluripotent so can give rise to all types of blood cells that we need in the body through a series of divisions and differentiations which are directed within the bone marrow by signalling factors.
How many cell divisions can haematopoietic stem cells undergo?
These haematopoietic stem cells have the ability to renew but this is limited to 50 cell divisions - this is known as the Hayflick Limit. This is defined by the progressive shortening of telomeres and when these get too short they can no longer divide. Each haematopoietic stem cell has the potential of producing about a million blood cells after 20 divisions.
What happens to the haematopoietic stem cells (what is the next step after the start of haematopoiesis?)
Haematopoietic stem cells can differentiate into haematopoietic progenitor cells and these progenitor cells are much more numerous and proliferative. From the haematopoietic progenitor cells, we get two main streams of blood cell development via a myeloid or lymphoid development. Myeloid cells will come from the common myeloid progenitor cells (CMP) and lymphoid cells will differentiate from the common lymphoid progenitor cells (CLP). These cells do not have the ability to renew.
Common myeloid progenitor cells
Common myeloid progenitor cells can differentiate into either erythroblasts to give rise to red blood cells or megakaryoblasts to give rise to megakaryocytes and platelets and myeloblasts which give rise to granulocytic cells such as neutrophils, basophils and eosinophils.
Common lymphoid progenitor cells
Common lymphoid progenitor cells can differentiate either into B cells, T cells and natural killer precursor cells.
Bone Marrow Stroma
Mesenchymal stem cells:
Adipocytes
Fibroblasts
Endothelial cells
Osteoblasts
Osteoclasts
What are the two different niches?
Two different niches: Osteoblastic niche and vascular niche.
What’s between these two niches?
Between these two niches are cells whose function is to provide matrix and growth factors to facilitate survival and proliferation and differentiation of cells in Haematopoiesis. E.g. collagen and glycoproteins such as fibronectin and thrombospondin, and glycosaminoglycans such as hyaluronic acid and chondroitin derivatives.
What is the name of an environment with no oxygen?
Hypoxic
Hypoxic
Environment with no/low oxygen concentration
Interleukins
Interleukins used for cell differentiation/activation
Chemokines
Chemokines used for cell migration
Interferons
Interferons used for cell activation
Colony-stimulating factors
Colony-stimulating factors used for cell production in bone marrow and cell activation
Tumour necrosis superfamily
Tumour necrosis superfamily used for cell activation and cell survival/death.
Actions of cytokines
Autocrine action: where the cytokine is secreted by a cell that binds to a receptor on the secreting cell
Paracrine action: cytokine is secreted from a cell that binds to a receptor on a neighbouring cell/ a cell that is close by.
Endocrine action: cytokine is secreted by a cell that is passed in the blood stream and activates a distant cell.
What do growth factors interact with?
Growth factors interact with growth factor receptors.
What is the most abundant cell in the body?
Red blood cells are the most abundant cell in the blood.
Platelets
Main function is to form the “platelet bug” in order to stop bleeding following injury (not cells but fragments of megakaryocytes)
Initiates wound healing/innate immune function.
Neutrophils
Short-lived, motile cell designed to phagocytose bacteria and combat tissue infection.
Multi-lobed nucleus allows extreme deformability (extravasation between endothelial cells - margination)
Neutrophils engulf bacteria to form a phagocytic vacuole. The cytoplasm granules fuse with the phagocytic vacuole (phagosome) to deliver bactericidal products.
Eosinophils
Host defence against nematodes and other parasitic infections
Secretes lysozyme, ROS and toxic proteins to kill parasite, and leukotrienes and prostaglandins to mediate inflammation.
Basophils
Are the only circulating leukocytes that contain histamine.
Tissue resident counterpart - mast cells
Activated by PAMPS and antigen crosslinking of FcꜪRI receptor-bound lgE to undergo rapid degranulation and release their cellular contents.
Monocytes
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 inflammation and chronic infections.
Types of T cells
T-helper and T-Cytotoxic
T helper cells
T-helper:
CD4+
Naïve
Effector (cytokines)
Memory
T-Cytotoxic cells
T-Cytotoxic:
CD8+
Naïve
Effector (Killer)
Memory
Exhaustion
T Cell Development
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.
B cells
Naïve B cells enter the blood and transit through spleen and lymph nodes tissue to encounter antigen.
Differentiate into: Memory B cells
Plasma cells (produce antibodies).
Natural Killer Cells
Innate lymphoid cells
Kill virally-infected cells through direct induction of lysis.
