BIO3CBH – Granulocytes and
Monocytes
Lecturer
Helen Irving
Intended learning outcomes for this lecture
(specifically relating to subject learning outcome 1)
By the end of this lecture, you should be able to:
• Distinguish different types of white cells in peripheral blood
• consider size, organelles, etc.
• Explain granulopoiesis and compare it to haemopoiesis
• Compare and contrast monocyte and granulocyte formation and function
• Explain what differences in neutrophil, basophil and eosinophil amounts in
FBE/CBC tell you about the patient’s health
• Analyse how malfunctions in granulopoiesis can contribute to disease states
• Analyse blood results in relation to granulocytes and monocytes and disease
states
Leukocytes (white blood cells) in normal peripheral blood
Task: note some features.
Neutrophils (~ 1,500-8,000/ μL)
Eosinophils (~ 0-450 / μL)
Basophils (~ 0-200 / μL)
Monocytes (~ 200-950 / μL)
Blood film stained with Romanowsky type dyes (e.g. eosin
and methylene blue) to differentiate white cell features
FBE/CBC –
WBC: differential versus absolute differential count
• Proportion of each leukocyte cell type is important in many diagnostic
tests
Absolute
Differential
differential
Absolute differential = percentages times total WBC
Source: https://upload.wikimedia.org/wikipedia/commons/thumb/6/69/Hematopoiesis_%28human%29_diagram.png/1200px-Hematopoiesis_%28human%29_diagram.png
By A. Rad - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=1042490
Stages of maturation of granulocytes
What are some of the key
features distinguishing
myeloblast and mature
segmented cells?
Which are found in the bone
marrow and which in the
blood?
Stages are the same for basophils, eosinophils and neutrophils, only the granules are different
How long does granulopoiesis take?
Diameter
16
24
Maturation time
14 days
no
yes
Mitotic
Granules
10-12 μm
no
azurophilic
Specific 20%
80%
Growth factors responsible for haemopoiesis
GM-CSF (granulocytemonocyte colony
stimulating factor),
interleukins (e.g. IL-3),
granulocyte stimulating
factor have varying
lineage specificities for
the granulocytes
Integration of factors determining neutrophil lifespan.
Neutrophils are also found in
“marginated pools,” vascular
pools located in the lungs,
spleen, and liver.
Key:
DAMPs – damage associated molecular
pattern molecules (AMPs)
PAMPs – pathogen AMPs
LPS – lipopolysaccharide
fMLF - formyl-methionyl-leucyl phenylalanine
HMGB1 - high-mobility group box-1
Carlos Silvestre-Roig et al. Blood 2016;127:2173-2181
©2016 by American Society of Hematology
Why are there so many neutrophils?
• Neutrophils are phagocytes
• Involved in first line of defence against invading pathogens
• Important mediators of inflammation induced injuries
• Neutropenia: _____________________________________
• Neutrophil leucocytosis: _____________________________
• Recent work suggests neutrophils are actually heterogenous population with
roles in shaping adaptive and innate immune responses (Silvestre-Roig et al. Blood
2016;127:2173-2181)
Source: Carlos Silvestre-Roig et al. Blood 2016;127:2173-2181
What do these results tell you about the blood of a patient?
CBC/FBE
• WBC 16,800 / μL
• Neutrophil 15,000 / μL
• Lymphocytes 1,400 / μL
• Eosinophils 340 / μL
• Hb 92 g/L
• MCV 86 fL
• Platelet count 140,000 / μL
• Task: Relate the white cell CBC
results to the blood film
Some changes in neutrophils due to bacterial infection
Dohle bodies - Inclusions found near the
plasma membrane of neutrophils usually in
neutrophil leucocytosis in response to
bacterial infection.
Toxic granulation - Coarse granulation
in neutrophils, another indicator of
bacterial infection
What do these results tell you about the differential white
cell blood count?
•
•
•
•
•
•
WBC 16.5 x 109 / L
Neutrophils 80%
Band cells 4%
Lymphocytes 12%
Eosinophils 4%
Basophils 0 %
•
•
•
•
•
•
WBC 17 x 109 / L
Neutrophils 66%
Band cells 14%
Lymphocytes 17%
Eosinophils 3%
Basophils 0 %
Source https://library.med.utah.edu/WebPath/HEMEHTML/HEME001.html
• Task: What do you think is meant by “left shift”?
Benign disorders – changes in neutrophil morphology
Source: https://commons.wikimedia.org/wiki/File:May-Hegglin_smear_2009-11-13.JPG
• May-Hegglin anomaly
Pelger-Huet anomaly
• Autosomal dominant uncommon condition
• Task: Compare and contrast the neutrophils? What makes them abnormal?
Neutropenia – a case history
• Samantha has received chemotherapy for her breast cancer. Samantha is
feeling unwell and feverish and attends her hospital (clinically upon arrival
she is febrile (e.g. >38°C). She is administered intravenous antibiotics within
60 min of admission followed by G-CSF in consultation with her clinician.
• The clinician orders CBC and carefully examines the absolute differentials at
12 hour intervals.
• Task: What is the clinician looking for? Explain.
What do these results tell you about the blood of a patient?
•
•
•
•
•
WBC 10,800 / μL
Neutrophil 7,700 / μL
Lymphocytes 2,400 / μL
Eosinophils 580 / μL
Basophils 120 / μL
Source: https://medlineplus.gov/eosinophilicdisorders.html
• Task: consider the WBC differential and
suggest possible causes and next steps
Eosinophils and basophils
• Eosinophils, enter inflammatory
exudates and have roles in local
immune responses and tissue repair
• Particularly allergic responses, defence
against parasites and removal of fibrin.
Normal
eosinophil
• Basophils rarely seen in normal peripheral
blood but are rapidly recruited to sites of
inflammation
• When stimulated, they release their
contents, including histamine, and
cytokines to aid immune responses ,
particularly against parasites
Normal
basophil
Monocytes and their derivatives
• Monocytes develop in bone marrow and spend some time in peripheral circulation
before entering tissues where they mature to macrophages with different tissue
determined functions
• Macrophages can self replicate and can live for months to years.
• Monocytes can also form dendritic cells involved in antigen presentation
Normal monocyte
Kidney:
Brain:
Serosal
Intraglomerular
microglia macrophages
mesangial cells
Lungs:
Liver:
Alveolar
Küpffer cells
macrophages
Spleen sinus:
Macrophages,
APC
Lymph node
Bone marrow:
Macrophages,
macrophages, APC
APC
APC = antigen presenting cell
Comparison of formation of monocyte and basophil phagocytes
From Hoffbrand & Moss (2016) Hoffbrand’s Essential Haematology 7th edition
Normal and abnormal monocytes
From: Lynch & Foucar (2016) Ask the Hematopathologists: Diagnostic Approach to Monocytosis
http://www.hematology.org/Thehematologist/Ask/5658.aspx; accessed 12/03/2018
Task: why is moncytosis associated
with chronic infections?
Questions and Next Lecture
• Next lectures will cover the lymphocytes and white cell disorders (see
notes to Haematology 3 and 4)