Haematopoiesis Flashcards
What is haematopoiesis?
Formation of mature blood cells from precursor cells.
Basic Constituents of blood:
50-60% plasma - contains soluble proteins and mediators.
The rest is the packed cell volume ~45%. This contains the haematocrit (RBC volume) - 42% and the WBC and platelets.
Number of RBCs, WBCs, and Platelets:
RBCs: 4-6 x 10^12 per litre
WBCs: 4-11 x 10^9 per litre
Platelets: 150-400 x 10^9 per litre
Start of Haematopoiesis:
i.e. what are blood islands:
Initially, blood islands are formed. These contain haematopoietic cells surrounded by ECs. These blood islands will form vasculature where the haematopoietic cells forms the circulating blood cells.
Sites of Haematopoiesis (prenatal and postnatal):
Prenatal:
- Liver and Spleen (extra medullary haematopoiesis)
Postnatal:
- Mainly the bone marrow (vertebrae, pelvis and sternum) - medullary haematopoiesis.
- Also occurs in lymph nodes at lower conc (esp in response to infection)
- in infection and pathological conditions, liver and spleen can also do haematopoiesis
Stem Cell Classification:
TOTIPOTENT - can differentiate into all cell types of an organism
PLURIPOTENT - can differentiate into endoderm, mesoderm and ectoderm. All blood cells have a common pluripotent stem cell precursor.
MULTIPOTENT - can differentiate into multiple cell types but is restricted.
UNIPOTENT - can differentiate to only one cell type (can’t self-renew)
Haematopoietic stem cells are multipotent and all circulating blood cells are derived from this.
Stages of Haematopoiesis:
This is a very organised process and is not random. Self-renewal, committed cells and developmental pathway occurs in bone marrow. Differentiation pathway occurs in tissues/plasma.
Haematopoietic stem cells can differentiate to either form the common myeloid progenitor cell lineage or the common lymphoid progenitor cell lineage.
Lymphoid progenitors can either form lymphoblast or immature dendritic cells.
1) Lymphoblast differentiate to form B- and T- lymphocytes and NK cells in plasma.
2) Immature dendritic cells enter tissues to form lymphoid dendritic cells (APC - links innate and adaptive immunity).
Myeloid progenitors can either differentiate to erythroblast, megakaryocytes, myeloblast, or monoblast.
1) Erythroblast when stimulated with erythropoietin can form RBCs in plasma.
2) Megakaryocytes when stimulated with thrombopoietin can form platelets in plasma.
3) Myeloblast - form neutrophils, eosinophils, and basophils in plasma.
4) Monoblast forms monocytes which become macrophages in tissue and can also form myeloid dendritic cells.
Role of neutrophils, basophils and eosinophils:
Neutrophils - needed in acute response to infection and inflammation.
Basophils - needed for allergy and parasitic infections.
Eosinophils - needed for allergy and sensitivity.
Organisation and macrostructure of bone marrow:
Arterial Supply:
Venous Drainage:
Where does haematopoiesis occur:
Arterial Supply:
Nutrient artery is the main blood supply of bone marrow. This enters into the medullary cavity through the nutrient canal. This then divides to form the ascending and descending branches. The radial artery which branches off from this, perforates the endosteum lining the medullary cavity and supplies the cortex as corical capillaries.
Venous Drainage:
This joins with periosteal and endosteal capillaries where they drain into the medullary vascular sinus (dense network through medullary cavity). This then drains into the central sinus which is removed from the bone marrow.
Haematopoiesis occurs in the extravascular space between sinuses.
Basic Characteristics of Blood Cell Types:
RBC, normoblast, reticulocytes Platelets, megakaryocytes Neutrophils Eosinophils Monocytes, Macrophages Lymphocytes - B and T Lymphocytes
RBCs:
- Diameter
- Lifetime
- Shape
- What does it consist of: does it have organelles and why is this useful?
- What happens to old RBCs?
- Diameter: 7μm
- Lifetime: 120 days
- Biconcave Shape
- No organelles - increases SA and allows deformation.
- Have Hb and enzymes (for anaerobic metabolism of glucose)
- old RBCs are removed by spleen and liver
Normoblast and Reticulocytes:
Characteristics of Normoblast:
Prior to formation of Normoblast:
Normoblast → Reticulocytes:
Characteristics of Reticulocytes:
Characteristics of Normoblast:
Normoblasts are formed in bone marrow which are 8-10μm in diameter and has a highly condensed nucleus. This still contains organelles and RNA which have to be removed.
Prior to formation of normoblasts, there are 4 key steps for erythroblast to undertake:
1) Transport iron via transferrin into cell into mito for heme synthesis
2) Form α and β-globulin chains which can then combine with heme to produce Hb.
3) Synthesise red cell proteins - enzymes
4) Undergoes mitosis until nucleus is highly condensed and inactive.
Normoblast → Reticulocytes:
Normoblast are released from BM where perforated sinus wall of vessels causes separation of RBCs from nucleus. This forms a reticulocytes.
Characteristics of Reticulocytes:
- have organelles and RNA which has to be removed in spleen - allows maturation of RBCs
~1% reticulocytes
Platelets:
- Diameter
- Lifetime
- Shape
- Function
Role of Platelets in Haemostasis:
Implications of Anuclear:
How are they produced:
How do their shape change in resting and activated state:
- Diameter: 2-4μm
- Lifetime: 8-12 days
- Shape: Discoid, anuclear
- Function: Haemostasis and Innate immunity
Haemostasis:
Platelets adhere to fibrin filaments and damaged ECs to prevent haemorrhaging - forms platelet clot.
Implications of Anuclear:
- limited de novo protein synthesis
- have granules which can release mediators
How are they produced:
Made from megakaryocytes in BM following stimulation by thrombopoeitin.
How do their shape change in resting and activated state:
At rest, platelets have a discoid shape and don’t aggregate.
When activated, platelets increase SA and become more flatter.
They then retract to form pseudoponia which allows them to aggregate with other platelets and form a platelet clot.
Megakaryocytes:
- Giant cells (50-75μm in diamater)
- single large irregular nucleus
- have platelet demarcation channels which partitions the cytoplasm - forms platelets
Neutrophils:
- what % of LKs are NTs?
- how many NTs are produced per day in BM?
- lifetime?
- nucleus: single or multiple
- differentiation and protein synthesis capability?
- motility?
- chemokine gradient
- is it the first cell recruited in inflammation?
- NTs in chronic inflammatory diseases (MS, RA)
- Granules?
Neutrophil Motility:
Neutrophil Phagocytosis:
- 60% of WBCs are NTs
- 10^11 cells are produced per day in BM
- Lifetime: 12hrs (Half life 6.7hrs)
- PMN - multilobular
- fully differentiated
- limited protein synthesis
- very motile
- follow chemotactic substance and engulf pathogens
- first cell recruited to site of inflammation
- these cells can damage healthy tissues if prematurely activated in chronic diseases such as rheumatoid arthritis and MS.
- have granules which contain anti-pathogenic substances to kill pathogens - proteases, microbicidial enzymes, acid hydrolases.
Neutrophil Motility:
Have uropods and pseudopods which retract to allow motility and have receptors allowing detection of chemokine gradient (released from pathogens), respectively.
Neutrophil Phagocytosis:
Can engulf pathogens and enclose in phagosome. This fuses with primary and secondary granules in NTs - pathogen is killed by hydrolytic enzymes.
Eosinophils:
- what % of LKs are eosinophils:
- nucleus: single or multiple
- motile?
- function
- diseases its associated with:
Morphology:
- what do they release?
- how long are they in circulation?
- cells prefer to enter?
- lifetime:
- when do their numbers increase?
- 1% of LKs are eosinophils - not seen in basal conditions
- PMN - bilobar
- motility to various chemoattractants
- function: kill parasitic infection
- associated with: hypereosinophilic syndromes, asthma and allergies and rhinitis.
Morphology:
- release cytotoxic substances to kill infection
- leave circulation 8-12hr following release from BM
- prefer to enter GI tract and sites of inflammation
- Lifetime: several days
- numbers increase in parasitic infections and allergic states such as asthma
Monocytes:
- diameter
- nucleus
- phagocytic and motile
- how long are they in circulation?
- what happens when they enter tissue?
- lifespan of macrophages
- Largest LK (20μm)
- single nucleus - kidney shaped
- highly phagocytic and motile
- leave blood within 2 days of release from BM
- enter tissues to become macrophages
- lifespan of macrophages: months/years
Functions of macrophages:
1) defend against microorganisms
2) remove tissue debris and old RBCs
3) antigen presentation during immune response (fragments of ingested antigen can be displayed on cell surface and presented to T lymphocytes to trigger an immune response)
4) Cytokine secretion - part of immune response and regulates haemopoiesis
Lymphocytes:
Small Lymphocytes:
- how many are small?
- diameter
- nucleus
- function
- types
Large Lymphocytes:
- diameter
- types and their function
Small Lymphocytes:
- most lymphocytes are small
- 6-9μm
- condensed nucleus (takes up 90% of cell - small cytoplasm)
- function: adaptive immunity
- types: B and T cells
Large Lymphocytes:
- 9-15μm
- types: activated B cells which are in transit to becoming plasma cells and NK cells (kill virus-infected or tumour cells by a mechanism not involving specific antigens)
B and T Lymphocytes:
B Lymphocytes:
- on surface?
- function?
T Lymphocytes:
- on surface?
- two types:
Helper T cells:
- marker?
- function
Cytotoxic T cells:
- marker?
- function
B Lymphocytes:
- have surface Ig (Ab - receptors for antigen)
- respond to antigen by proliferating and maturing into plasma cells which secrete the same Ab
T Lymphocytes:
- have receptor for antigen (TCR)
- two types: helper and cytotoxic
Helper T cells:
- CD4 marker
- respond to antigen by secreting cytokines that help other lymphocytes
Cytotoxic T cells:
- CD8 marker
- kill virally infected cells
