Leucocytes: Production and Function Flashcards
What is the production of Basophils, eosinophils, neutrophils, platelets, and monocytes called?
Granulopoeisis
What are the 3 cell types that have granules?
Eosinophils
Basophils
Neutrophils
What stimulates granulopoeisis?
Cytokines with orderly sequence of maturation
IL-3
Granulocyte colony Stimulating Factor
What is the band form?
The immediate precursor of the neutrophil
What is granulopoeisis?
Hemopoeitic stem cell undergoes specific differentiation in response to cytokines with orderly sequence of maturation.
Where in the bone marrow does granulopoeisis take place?
Maturing forms deeper in the marrow space
How is the nucleus positioned in the early precursor to granulocytes?
It is positioned eccentrically (off to one side)
What happens to nucleus during granulopoeisis?
Nucleus shrinks and moves off to one side.
Early precursors are located adjacent to the bony trabeculae and then after maturation they form deeper in the marrow space.
Why are early precursors located near the bony trabeculae?
Due to achieving cytokines from near that location
What early precursor do neutrophils develop from?
Primitive myeloblast
What are the stages of neutrophil formation?
Myeloblast
Promyelocyte
Myelocyte
Metamyelocyte
Band form
Neutrophil
What happens to neutrophils during maturation?
Reduction in size
Contain fine granules which develop (primary and secondary (specific) cytoplasmic)
Neutrophil nucleus segments (2 - 5 segments
What happens to neutrophils during maturation?
Reduction in size
Contain fine granules which develop (primary and secondary (specific) cytoplasmic)
Neutrophil nucleus shrinks and then segments (2 - 5 segments)
Neutrophil then leaves bone marrow and then acts as a phagocyte and discharges granules into bloodstream.
What happens to female neutrophil nucleus?
females have a drum stick like appendage (20% of the time)
What are primary granules?
Early granules of many functions
When are primary granules formed?
At promyelocyte stage
How do primary granules look on electron microscope and how do they differ from secondary granules?
They are electron dense and larger than secondary granules
What do primary granules contain?
Lysozyme
Defensins
Elastase
Cathepsins B, D and G
Proteinase 3
What do secondary granules contain?
Lysozyme
Transcobalamin I (vitB12 binding protein)
Collagenase
beta 2 microglobulin
Lactoferrin
How are secondary granules different to primary granules?
They are specific to neutrophils. Primary granules are also located in basophils and eosinophils
What causes variation in number and lifespan of neutrophils?
Age, gender, ethnicity
How does mature neutropil migrate from BM to blood?
It migrates through the sinusoidal endothelium (through diapedesis)
How long do neutrophils last in blood for?
Half life in blood is 2.6 - 11.8 hours (mean 7.2 hours)
How long can neutrophils survive outside of the blood?
Up to 30 hours
Can neutrophils appear in secretions and tissues?
yes and they can live for 30 hours outside the blood
Are WBC counts higher at birth or at 18 years old?
They are highest at birth and drop by the time we are 18
What causes neutrophil count to go up?
Infection
Acute inflammation
Stress
Pregnancy
Surgery
Trauma
Tissue damage
Infarction
Steroids and cytokines
What are the second most frequent granulated cells?
Eosinophils
How is development of eosinophils different to neutrophils?
Eosinophils develop secondary granules at the myelocyte stage
What is the diameter of eosinophils?
12 - 17 micrometers (slightly larger than neutrophils)
What do eosinophilic cytoplasm contain?
Large round granules
What colour do eosinophils look with romanowsky stains?
Red-orange
How many lobes do eosinophil nuclei contain?
2 lobes that look like glasses and a bridge
What is the half life of eosinophils in circulation?
4.5 - 8 hours
How long can eosinophils survive in tissues?
8 - 12 days
What percentage of WBCs are eosinophils?
1 - 5%
What causes acute allergic response?
Eosinophils (their count increases in response to allergies)
What do eosinophil granules contain?
Phospholipases
Histaminase
Ribonuclease
Beta glucuronidase
Cathepsin
Collagenase
What guides the mobility of eosinophils?
Chemotactic agents, phagocytose and kill microorganisms
How effective are eosinophils at phagocytosis compared to neutrophils?
Slower at ingesting and killing bacteria than neutrophils
What type of pathogens and immunoglobulins do eosinophils bind to?
IgG and C3 coated helminths
Which cells are involved in immediate -type hypersensitivity reactions / allergies?
Eosinophils
What causes an increase in eosinophil count?
Allergy
Drugs
Asthma
Dermatitis
Parasites
Neoplastic syndromes (They can get cancer)
What are the most infrequent Leucocytes seen?
Basophils (<1%)
What do basophil nuclei look like?
Has 2 segments but often hard to see due to being covered by purple-black cytoplasmic granules
What cell surface receptors do basophils have? Why?
IgE, IgG, C5a, histamine, chemokines
What do basophils have in their granules?
Histamine
Mucopolysaccharides
Peroxidase
Chymase (a serine protease)
Tryptase
When do we see more basophils?
Chronic myeloid leukaemia and in this condition they have reduced number of granules
Are monocytes granulocytes?
They have granules but are not called granulocytes
What percentage of white blood cells are monocytes?
2 - 8%
What influences maturation of monocytes from stem cells?
IL-3 and GMC
What stem cells do monocytes come from?
Monoblast
What does the nucleus look like on monocytes?
Horseshoe shaped
How long is monocyte half life in the circulation?
70 hours and then they move into tissues to become macrophages
What is the largest leucocyte?
Monocytes/macrophages
What do macrophages do?
Collect debris from blood and tissue
Store iron
What do monocyte granules contain?
Enzymes: Acid phosphatase, esterases, galactosidases
Lysozyme, MPO, Elastase, defensins, collagenase
Coagulation system proteins (TF, Factors V, VII, X, and XIII, plasminogen activator)
Where are monocytes most effective?
In long-term conditions and inflammation
When do we see a large number of monocytes?
Chronic myelomonocytic leukemia
Chronic infections / inflammation
What chemical messengers do monocytes react to?
IgG-Fc and C3 membrane receptors
Chemokine receptors CCR2 and CCR5
What do lymphocytes do?
Cell mediated immunity and antibody secretion
Where are lymphocytes produced?
Bone marrow and some move to thymus and continue there.
What is normal T:B ratio?
6:1
What percentage of BM cells are lymphocytes?
10 - 15%
What percentage of WBCs are lymphocytes?
20 - 45%
What shape are lymphocytes?
Round cells with a round nucleus that is slightly indented
What ages are lymphocyte counts at their highest? What is favoured at early and late ages B cells or T cells?
Early childhood with B cells being favoured initially over T cells and then that switches in adulthood.
What percentage of lymphocytes are T cells, B cells, and NK cells?
T (70 - 85) B (5 - 25) NK (<5)
What is the most common leukemia?
Chronic lymphocytic leukemia
What cells secrete antibodies?
Plasma cells
What percentage of plasma cells are located in the marrow?
<3%
Where in the bone marrow do plasma cells line up?
Near the blood vessel (presumably to produce antibodies directly into the circulation)
What do plasma cells look like?
Eccentric (non centered) nucleus.
Clumped chromatin
What kind of antibodies do plasma cells produce?
Monoclonal antibodies (CD138 and cytoplasmic light chains)
What kind of malignancies can plasma cells undergo?
Multiple myeloma
Plasmacytoma
What organelles are abundant in plasma cells?
Golgi apparatus and Rough ER which are present all in a pale region within the cell
What are megakaryocytes?
Large cells with hyperlobated nucleus.
What do megakaryocytes do?
They generate platelets (cytoplasmic fragments)
What kind of mytosis produces platelets from megakaryocytes?
Endomitosis (nuclei undergo huge number of copies (128+ copies))
Where are megakaryocytes located?
They are centrally located intratrabecular and peri sinusoidal.
Where do megakaryocytes come from?
Come from common myeloid progenitor cells
What cytokines influence platelet production?
IL-3 and thrombopoietin
