Leucopoiesis

Lesson Objectives

At the end of the lecture students

should be able to:
• Describe the process of leucopoiesis
• Differentiate myeloid cells
• Recognise myeloid cells
• Recognise lymphoid cells
• Describe the structure of leucocytes
• Describe the function of leucocytes
Leucopoiesis

• The development of white blood cells (WBCs) except

lymphocytes occurs in the same location as
erythropoiesis

• Leukocytes – exist to defend the organism against non-

self agents through intricate cooperation among cells

• Subdivided as granulocytes containing large granules

(neutrophil, basophil, eosinophil) and agranulocytes
(monocytes and lymphocytes)
Granulocytes

Can be found in four locations also called granulocyte pools:

a) In the bone marrow
b) Circulating in peripheral blood
c) Marginating against the endothelium of blood vessels
d) In the tissues
 Bone Marrow Pool
Has 3 functions:
a) Proliferation
b) Maturation
c) Storage

• Proliferating component – contain cell capable of mitotic divisions

(myeloblasts, promyelocytes, and myelocytes)
• Maturation component – contain cells that are incapable of mitosis
but not yet fully functional (metamyelocytes and bands)
• Storage component – contains bands and polymorphonuclear
leukocytes
• Circulating pools contain approximately 50% of total peripheral blood
granulocytes levels and the other 50% in the marginating pools
Stem cell to Myeloblast

• Hematopoietic stem cell – mature into a stem cell specific for

bone marrow-derived or myeloid cells (CFU-GEMM)

• CFU-GEMM – matures into another progenitor cell called the

colony-forming unit granulocyte-monocyte/macrophage (CFU-
GM)

- this is controlled by a complex of interaction humoral factors,

such as interluekins and CSFs
• Usually 15-20 micrometers Myeloblast
• Nucleus is delicate with
prominent nucleoli
• Cytoplasm contains RER,
developing Golgi apparatus,
and the initial presence of
primary or azurophilic granules
• The granules colours positive
for enzyme
MYELOPEROXIDASE
• Incapable of motility,
adhesion, and phagocytosis
• < 1% in the normal bone
marrow compartment
• Size may exceed 20 micrometers
• Nuclear chromatin pattern may Promyelocyte
show slight clumping (Proganulocyte)
• Nucleoli begin to fade
• Dominant characteristic of
PRIMARY GRANULES
• Motility may be present
• 1 to 5% in the bone marrow
reduced nicotinamide adenine
dinucleotide phosphate oxidase
and flavocytochrome B – activates
neutral proteinases cathepsin G,
elastase, proteinases for killing to
take place
• <10% of the total marrow cell
population Neutrophilic
• Nucleus may be round to oval with Myelocyte
flattened side near Golgi apparatus
• Nuclear chromatin shows clumping
and nucleoli no longer visible
• characteristic is the production of
SECONDARY OR NEUTROPHILIC
granules
• Last stage capable of mitosis
• Second of the 3 major type of
granules is synthesized causing
“dawn of neutrophilia or faint blush of
pink near the Golgi apparatus
• Result after the cessation of all active
DNA synthesis Neutrophilic
• Nucleus is indented Metamyelocyte
• Cytoplasm has collection of primary
and secondary granules ( major feature
of cytoplasm)
• The granules constitute the major
component necessary to kill and
degrade non self agents
• Incapable of reacting to chemotactic
factors
• 13 – 22% of normal bone marrow
differential
• Band shape, a transitional form
because it is considered to be part of Neutrophilic Band
maturation and storage pools in the (Nonsegmented
bone marrow and peripheral blood Form)
• constitutes 40% of white blood cells
but < 6% in the peripheral blood
• Non segmented
• Nucleus have uniform or parallel width
• Nuclear indention is less than half the
width of the nucleus (horse shoe
shaped)
• Possess full motility, adhesion
properties and phagocytic ability
• Membrane is characterized by changes
in the cytoskeleton, surface charge and
presence of receptors
 Phagocytosis
• chemotactic factors cause the polymorphonuclear cell to migrate to
source
• Neutrophils periodically determine whether the vessel endothelium is
expressing surface molecules, which enhance a more firm contact
(adhesion)
• Egress of neutrophil outside the blood circulation (diapedesis) in
response to chemical gradient
• It adhere to particles that initiated the attraction then pseudopods
extend the around the particle, engulfing it and forming a phagosome
• Cytplasmic granules combine with the phagosome forming
phagolysosome and dump their contents in it
• Primary granules – contribute to proteolysis
• Secondary granules – increase complement fixation and chemotactic
response
- causes degradation and detoxification of material
Eosinophil Maturation

• Prominent secondary granules are stained heavily with the

eosin dye with Romanowsky based stains
• Requires IL-3, IL-5 and GM-CSF and inhibited by interferon
• Developed from CFU-GEMM to CFU-Eo
• Similar to neutrophil in the myeloblast and promyelocyte stage
• In the myelocyte stage, it is distinguish from neutrophil by presence
of numerous large round granules containing crystalloid compound
compromising major basic protein
• Its granules contain proteolytic enzymes but no secretory vesicles
• Nucleus with 2 or 3 lobes connected by
thin strand
Eosinophil
• Large, uniform sized granules stain
orange red with acidic dyes that do not
obscure the nucleus
• 10 – 14 microns
• 1 -3 % of circulating WBCs
• Large dark purple variable sized
granules stain with basic dyes that
obscure the nucleus Basophils
• Irregular shaped bilobed nucleus
(more than two lobes are extremely
rare)
• 0 – 1% of circulating WBCs
• Have specific high affinity for the Fc
region of IgE
• Involved in allergic inflammation and
initiate localized and system
anaphylaxis

- granules contain heparin, chondroitin

sulfate, histamin, serotonine, and other
vasoactive and immunomodulatory
mediators
 Questions
1. last stage of granulopoesis that is capable of mitosis
a) Myeloblast b) promyelocyte c) myelocyte d) metamyelocyte

2. neutrophil maturation stage where it is part of both storage and maturation pool in
the bone marrow
a) Metamyelocyte b) band c) myelocyte d) segmented neutrophil

3. responsible for the staining of the granules of eosinophils

a) Major basic protein b) peroxidase c) proteolytic enzymes d) myeloperoxidase

4. the common myeloid progenitor

a) CFU-GM b) GM-CSF c) CFU-GEMM d) G-CSF

5. involved in allergic inflammation and initiate localized and system anaphylaxis

a) BAND neutrophil b) basophil c) PMN d) eosinophil
Leucocyte structure and
function
 Classified according to the presence or
absence of granules and the staining
characteristics of their cytoplasm.
 Leucocytes appear brightly colored in
stained preparations, they have a nuclei
and are generally larger in size than
RBC’s.
Types of lecocytes
 Granulocytes—have large
granules in their cytoplasm

 Neutrophils
 Eosinophils

 Basophils
Types of WBC’s
 Agranulocytes—do not have
granules in their cytoplasm

 Lymphocytes
 Monocytes
 Granuloctyes
 Neutrophils
 Stain light purple with neutral dyes
 3-5 lobes in nucleus
 65% of WBC count
 Highly mobile/very active
 Diapedesis—Can leave blood vessels and enter
tissue space
 Phagocytosis (eater), contain several lysosomes
(janitor)
Neutrophils
•Very fine granules that respond to
both acid and basic stains
•The cytoplasm as a whole stains
pink
•Neutrophils are avid phagocytes at
sites of acute infection
 Granulocytes
 Eosinophils or Acidophils:
 Large, numerous granules
 Nuclei with 2-3 lobes
 2-5% of WBC count
 Found in lining of respiratory and digestive tracts
 Important functions involve protections against
infections caused by parasitic worms and
involvement in allergic reactions
 Secrete anti-inflammatory substances in allergic
reactions
 Basophils
 Least numerous--0.5-1%
 Diapedesis—Can leave blood vessels and enter
tissue space
 Contain histamine, serotonin,
heparin—inflammatory chemical
 Histamine is an inflammatory chemical that
makes blood vessels leaky and attracts other
WBCs to the inflammatory site
 Agranulocytes
• lack visible cytoplasmic granules
• Their nuclei are spherical oval or kidney-shaped
• The agranulocytes include lymphocytes and
monocytes
 Agranulocytes
 Lymphocytes
 Smallest WBC
 Large eccentric nuclei
 small amount of cytoplasm (scanty)
 Account for 25% of WBC count
 Two types—T lymphocytes—attack an infect or
cancerous cell, B lymphocytes—produce
antibodies against specific antigens (foreign
body)
 Agranulocytes
 Monocytes
 Largest of WBCs
 Dark kidney bean shaped nuclei (indented
nucleus)
 Highly phagocytic
 Abundant cytoplasm
 When they migrate into the tissues, they change
into macrophages
 Macrophages are very important in fighting
chronic infections, such as tuberculosis
Lungs- Alveolar macrophages
Liver- Kupffer cells
Pleural cavity- Serosal macrophages
Lymphoid tissue- macrophages
Bone- Osetoclasts
• The granulocytes and the monocytes protect
the body against invading organisms by
ingesting them by the process of phagocytosis
• The lymphocytes function mainly in connection
with the immune system. However, a function
of certain lymphocytes is to attach themselves
to specific invading organisms and destroy
them, an action similar to those of the
granulocytes and monocytes
Leucocyte Numbers

• A decrease in the number of white blood

cells is leucopenia
• An increase in the number of white blood
cells is leucocytosis.