BL 16 Flashcards
Define haematopoiesis
Haematopoiesis is the formation of blood cellular components
What can bone marrow stem cells differientiate into?
Only has the potential to differentiate into different cells found in the blood
What are common progenitors (what are they formed from, what happens next, how many are there?)
Learn the first box in the diagram
- Found in the bone marrow
- Large bank to fuel cells of the blood
- Haemopoietic stem cells have the ability to self replicate and differentiate further (into different types of blood cells)
- Common progenitors only have the ability to differentiate into lineage bound
- Constantly replicating and differentiating driven by multiple hormones and chemical messengers
- They can’t go back and undifferentiate
Blood cell selection (describe what is meant by this)
- Not all cells found in the bone marrow will end up in the blood
- Some will undergo programmed cell death (apoptosis)
- For example, 250 million erythrocytes (Red blood cells) formed per day
However this is only a proportion of the progenitor cells involved in the overall process i.e rates of upto 40% survival in certain stages of erythropoiesis
Why do blood cells go under programmed death?
2 reasons:
- A way of quality control
- Apoptosis can also happen randomly
Describe how erthyroctyes are formed (include the important regulation hormone)
Look at diagram (box)
- Erythropoietin is the important regulatory hormone
Process:
- Erythroblasts start of with large nucleus, prominent nucleoli and large amounts of RNA
- Nuclear material becomes more dense
- Gradually nucleus shrinks and is removed along with majority of RNA (nucleus is removed in nuclear extrusion)
What is the life span of a RBC?
120 days
How many molecules of oxygen does a RBC contains?
1 billion
How long does it take for one RBC to circulate around the body once?
20 seconds
Why do people with ethryoctye abnormalities have enlarged livers and/or spleens?
The two organs are needing to take up many more ethryocytes as more are abnormal
Describe the structure of erthrocytes (RBC)
- Biconcave shape to increase surface area for diffusion of gases
- No nucleus/minimal organelles to maximise oxygen holding capabilities
- No mitochondria to ensure oxygen is not used up by erythrocyte
- Haemoglobin to increase affinity of oxygen binding (made from iron)
Why do RBC not have mitochondria
If there were mitochondria the erythrocyte would be using up the oxygen it is transporting instead of delivering it to the tissues (respire via anaerobic respiration)
What does ‘blast’ mean?
Immature blood cell
What are reticulocytes? (where are they formed, what remains, when are reticulocyte levels high?)
- The final step before a mature erythrocyte
- Formed after nuclear extrusion (the reticulocytes are formed in the penultimate step before forming the the erythrocyte)
- Only a small amount of RNA remains in the reticulocytes to help make haemaglobin
- The remaining RNA is then removed in 1-2 days
- High amounts of Reticulocytes can present in the blood when the body is recovering from blood loss
Label the cells in this diagram
- Reticulocytes (cells that have a bit of RNA left in them)
- Erythrocyte
What happens when you lose lots of blood?
- Kidney senses tissue hypoxia (low oxygen)
- The kidney increases secretion of erthropoietin
- This hormones increases the number of erthyrocytes in the blood, very quickly (see next flashcard)
What is erythropoietin and what is it’s role?
- A glycoprotein produced by the kidney to increase levels of red blood cells
- It Is produced by the kidneys in response to tissue hypoxia (e.g. caused by blood lose)
- Role: Acts to stop programmed cell death (apoptosis) of erythrocyte progenitors. This increases the number released in the blood
- Made in the liver during fetal life and is taken over by the kidney around birth
What are granulocytes?
Sub-group of WBC, includes:
- Basophil
- Neutrophil
- Eosinophil
Describe the process of forming granulocytes and the hormone
What is another name for granulocytes
Polymorphonuclear cells/polymorphs
What is the role of granulocytes/polymorphonuclear cells
- Sub group of white blood cells- fight infections/ inflammation
- Thus named due to the presence of granules within their cytoplasm
- All act to mediate inflammatory reactions in the body (so they increase inflammation)
- All act by releasing cytokines, interleukins, leukotrienes etc. which recruit various other immune cells
Approximate sizes of the granulocytes
Consist of (size):
• Neutrophils (12-15µm)
• Basophils (11-14µm)
• Eosinophil (10-12µm)
Neutrophils (role, discription of structure)
- Often first responder and first line of defence against bacteria
- Can kill bacteria in multiple ways
- Multilobed nucleus
- 3 types of granules
- Most abundant of the granulocytes
On the picture attached:
- multi-lobulated nucleus
- specs are the granules
Function of a neutrophil
- Granules contains lysozomes, matrix metalloproteinases (MMPs) and gelatinase (lysozoymes will break down pathogens the neutrophil engulfs)
- Phagocytosis (engulfing the pathogen)
- The middle person i.e signalling and antigen presentation (signalling other immune cells to do things)
- Neutrophil Extracellular traps (NETS) - chromatin nets (these will be sent out by the neutrophils, it will capture lots of pathogens and keep them in one place to then be destroyed)
- Respiratory burst (e.g. make free radicals to then cause death)
Phagocytosis
How does Respiratory burst work?
The free radical produced causes respiratory burst
What is the role of G-CSF?
- G-CSF is secreted by multiple immune cells in the body and endothelial cells
- Usually released in response to inflammation or infection
- G-CSF acts on the bone marrow to increase the number of circulating neutrophils
- G-CSF increases the speed at which nuetrophils mature as well as the numbers (usually it take 12-14 days for neutrophils to mature, but G-CSF causes them to mature in 12 hours)
Basophils (role, structure)
- Release histamine to trigger inflammation
- Mediate hypersensitivy reactions (eg asthma)
- Bilobed nucleus
- Purple granules (stained due to basic dye)
- Granules contain histamine and heparin
What is the role of histamine?
- Vasodilation of vessels (to increase blood supply and number of cells in a certain area). (Inflammed areas will be hot and swollen due to increase blood flow)
What is the role of heparin?
Blood thinner - if increasing number of cells and blood in one area, it will become very viscose, to stop this clotting risk, heparin is also released
Eosinophils (role, structure)
(Just need to be aware that there are specific WBC with anti-parasitic properties
- Phagocytose pathogens (yup - also phagocytose)
- Fight parasitic worms and have a role in inflammation/allergy ?(anti-inflammatory - as they contain histaminase - but scientists are too sure)
- Granules contain: antihelminthic proteins such as major basic protein and eosinophilic cationic protein, Cell component destroying enzymes (eg phosphlipases and acid hydrolases)
- 2 nucleur lobes
- Spheric granules- eosinophilic (acid-loving) granules
What 2 major processes do all granulocytes go through when forming?
All 3 lineages go through the process of:
• Nuclear condensation and lobulation
• Formation/increased numbers of granules
How do monocytes/macrophages form?
Role of monocytes/macrophage (names, role)
- Monocyte in the blood- macrophage in the tissue (in the blood they are called monocytes, in the tissue they are called macrophages - location changes their names)
- First line of defence
- Phagocytose pathogens, cell debris and senescent cells (Best phagocyte)
- Present foreign antigens i.e raise the alarm, to other WBC
- Largest of all mature blood cells (12-17µm)
- Unilobular ”horseshoe” shaped nucleus
What cell is this?
Neutrophil (Neutrophils are granulocytes characterised by a multilobulated nucleus)
What cells is this?
Basophils - Basophils look very similar to mast cells in that the grabules they contain have sulphur in them and so attract haematoyxylin. The sheer number of franules often totally obscures the nucleus and so that cannot be seen).
What cell is this?
Eosinophils - Eosinophils are granular cell that are easily recognised because their granules take up the red stain that gives them their name
What cell is this?
Monocyte - Monocyte are agranular cells that have a characteristic U-shaped or horseshoe shaped nucleus. There are sometimes difficult to determine when viewed end on. They become tissue macrophages (histiocytes) when they enter tissues, i.e. Kupffer cells in the liver)
What cell is this?
Lymphocytes - Lymphocytes have a large purple nucleus with the cytoplasm as a rim around the edge of the cell
What is thrombopoiesis? What hormone is involved?
Making platelets (thrombocytes) in a process called thrombopoiesis. - Thrombopoietin will increase the number of platelets in the body
Describe the process of making thrombocytes (platelets)
Platelets (other name, function, size, shape, structure and contents)
- Thrombocytes
- Function to stop bleeding and mediate haemostasis
- 2-3 µm in size (very small)
- Biconvex shape
- No nucleus- just cytoplasm
- However, not so simple, contains vast amount of proteins and clotting factors (e.g. lots of ribosomes and very metabolically active)
- Have special receptors on surface which causes platelet aggregation (make platelets stick together and form a plug) (gpIIb/gpIIIa)
Label the diagram
- RBC (circles)
- Platelets (small dots)
What is the hormone involved in making platelets?
Thrombopoietin
How is thrombopoiesis increased?
- Upregulated by thrombopoietin from the liver
- Formed from a megakaryocyte breaking down which eventually forms 2000-3000 platelets
What is lymphopoiesis?
The formation of the following WBC:
3 types:
• B Lymphocyte
• T Lymphocyte
• (Natural killer cell)
Describe the process of lymphopoiesis
B lymphocytes (other name, function, type of immunity, maturation occurs?)
- Main function revolves around production of antibodies
- Each B cell is specific to a specific antigen
- Can activate T cells
- Play a part in humoral adaptive immunity (leads to making of antibodies
- Maturation occurs in the bone marrow and then in: Intestines (peyers patches), Spleen, Lymph nodes
T lymphocytes (other name, function, type of immunity)
- Kill virus-infected cells, neoplastic cells and transplanted tissue
- Carry out cell-mediated immunity
- Activate B cells to make antibodies using IL 4
- Large nucleus with small rim of cytoplasm (can see this in the attached diagram)
- Proliferation and activation caused by IL 2
- Microscopically indistinguishable from B cells (6-9µm)
Where do the T lymphocytes mature?
- T cells start off in the bone marrow or fetal liver and then will migrate to the thymus to mature
- After this they will migrate to secondary lymhoid organs (e.g. tonsils, spleen, lymph nodes, appendix) where they will wait until activation
Site of haemopoiesis (where did it mostly occur before birth? where does it mostly occur after birth?)
- Before birth: Yolk sac and then liver
- After birth: Bone marrow
Plasma (where is this found, composition, what proteins are in it?)
• Makes up the majority of circulating volume
• The supporting medium for all circulating blood cells
• Constituted of approximately:
92% Water
8% protein
Ions (Na, K, Cl, etc.)
• Protein component hugely important: Albumin (liver), Clotting factors (liver), Hormones, cytokines, antibodies etc.
What is plasma and what is serum?
- Serum: Plasma without the RBC, WBC, platelets and clotting factors
What does a low INR mean?
Means how thin the blood is, high INR = Blood is more thin so more at risk of bleeding
Why do alcoholics often bleed too much?
- Damaged liver - liver makes clotting factors and thrombopioetin (so low platelets), so blood can’t clot easily
