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HONOR DEGREE IN HEMATOLOGY
Lecture 5
 Def: Formation and maturation of white blood
cells.
 Granulocytopoiesis
 Agranulocytopoiesis
–Monocytopoiesis
–Lymphoctye maturation
 There are 3 different areas in our body
where different WBCs reside:
1. Marrow pool: 90% neutrophils
2. Blood pool: 3%
3. Tissue pool: 7%
 In bone marrow → PHSC (Pluripotential
hemopoietic stem cells) differentiates →
committed stem cells → CFU-GM
 Granulocytes & monocytes are formed only in
bone marrow.
 lymphocytes & plasma cells are produced in
various lymphogenous tissues
 Granulocytes and monocytes are formed from bone
marrow, which is derived from CFU-GM(colony forming
units of granuloctyes and monocytes)
 The progenitor cells [CFU-GM] forming different cells
are further named as;
- CFU-G= neutrophil forming units
- CFU-E= eosinophil forming units
- CFU-B= basophil forming units
- CFU-M= monocyte forming units
 Development of granulocytes-includes various
stages called
Myeloid series
 Development of monocytes –includes various stages
called
Monocytes-macrophages series
 Process of granulopoiesis-12 days
 Granulocytes are formed and stored in the bone
marrow –when needed it is released in the circulation
 Regulated by growth factors, CSF & Interleukins
 Granulocyte maturation divide into six stages.
 All of the granulocyte derive from myeloblast
 Structural Changes during differentiation &
maturation:
A. A decreased in cell size
B. Condensation of nuclear chromatin
C. Changes in nuclear shape
D. An accumulation of cytoplasmic granule
6
5
4
3
2
1
 It is the earliest recognizable cell of the granulocyte
series:
 Size:16-20um
 Cytoplasm: basophilic
 Present as thin rim aroundthe Nucleus
 Devoid of granules
Nucleus: Large nearly filling the cells round to oval,
Fine chromatin, 2-5 well defined pale nucleoli
Mitosis: marked [+++].
 Size: 14-18um
 Cytoplasm : increased in amount
 Presence of azurophil granules [primary
Non specific granules]
 Gives +ve reaction with the peroxidase
Staining
 Nucleus: round or oval
 Slightly smaller than myeloblast nucleus
condensed fine chromatin
 Nucleoli present-less prominent
 Mitosis: characteristic feature{+++}
 Size: 12-16um
 Cytoplasm : specific secondary granules present identified
at this stage as;
- Neutrophil myelocyte
- Eosinophil myelocyte
- Basophil myelocyte
 Primary granules are also presentat this stage but their
formation is stopped
 Nucleus: eccentric, round-oval
 Coarse nuclear
chromatin .
 No, nucleoli present
 Mitosis: continues up to this stage
 Multiplication of these cells are maximum
 Size: 10-14um
 Cytoplasm: increased in amount
- More liquid
- Primary and secondary granules are present according to
secondary granules it is distinguished as;
• Neutrophil metamyelocyte
• Eosinophil metamyelocyte
• Basophil metamyelocyte
 Nucleus: decrease in size
 Lobed (horse shoe shaped)
 Nuclear chromatin is dense and
clumped nucleoli are absent
 Mitosis: stopped at this stage.
 Also called juvenile granulocytes
 Size: smaller than metmyelocytes
 Cytoplasm: pink and fine evenly distributed
granules
 Nucleus: further condensation of
chromatin
- Shape: band configuration [v shaped] of
uniform thickness which may be twisted.
- Diameter = 10-12 m
- Cytoplasmic granules stain pale lavender
- Lobed nuclei (3-5 lobes)
- % of total leukocytes: 50-70%
- Drumstick: inactive X-chromosome
Granules contain lysosomal enzymes and
defensins
Neutrophils are quick acting phagocytes (1st
responders)
They are quick but weak!
Typical Neutrophil
1. NEUTROPHIL (POLYMORPHONUCLEAR CELL)
 Diameter = 10-14 m
 Large granules which stain red (major basic protein)
 Bilobed nucleus
 Represent 2-4% of the total WBC count
Granules contains and functions:
Granules contain digestive enzymes
Are antiparasitic
Phagocytize immune complexes
Anti-allergy
2. EOSINOPHIL
 Diameter = 8-10m
 Large granules which stain blue
 U or S shaped nucleus
 0.5 – 1% of total WBC
Granules contain:
histamine which induces inflammation and vasodilatation
heparin an anticoagulant
3. BASOPHIL
 All of the granulocyte derive from myeloblast
 Myelocyte is the stage when three types of granulocyte
can be recognized
 The maturation process of granulocyte characterized by :
– synthesis of azurophilic and specific granules
– Condensation of nucleus
 Mature granulocyte leave the bone marrow then enter the
circulation connective tissue
1
2
3
4
 It is the larger cell, similar to myeloblast
1
 It is an young monocyte
 Size: 20um
 Nucleus: larger
- Kidney shaped one nucleoli
- Nuclear chromatin: arranged in aloose
network
 Cytoplasm: basophilic
- No azurophilic granules
-They have fine granules which is larger than mature
monocytes
2
Are phagocytes – slow but strong
Develop into macrophages when they migrate into
connective tissue
3. MONOCYTES
Diameter = 18 m
Nucleus is U shaped or kidney shaped
Abundant pale blue cytoplasm
3 – 8 % of the total WBC
 Once the monocyte enters
the tissues, it becomes a
macrophage
 Size:15-80µm
 Cytoplasm
▪ Gray-blue and abundant
▪ Ragged edges
▪ Vacuoles common
Nucleus
Round with netlike
appearance
Purplish with finer
clumped chromatin
 Nucleoli appear
2
1
3
4
B. lymphocyte
 Cell size: 10-20µm
 Cytoplasm
▪ Blue/scanty
▪ No granules, Auer rods are never present
 Nucleus
▪ Purple, smooth chromatin
▪ Round, central or eccentric
▪ 1-2 nucleoli
 N:C ratio = 4:1
 Size: 9-18µm
 Cytoplasm
▪ Blue, scanty
▪ Usually granules are absent, but a few azurophilic granules may be
present
 Nucleus
▪ Purple, condensed chromatin
▪ Round or indented, eccentric
▪ 0-1 nucleoli
 N:C ratio = 4:1
 LYMPHOCYTES T-LYMPHOCYTES
 LYMPHOCYTES B-LYMPHOCYTES
 LYMPHOCYTES B-LYMPHOCYTES
Thymus
Liver
Bone
 Diameter 5-8 m (small), 10-12 m (medium) or 14-17 m (large)
 20-25 % of the total WBC count
 Large, deep blue or slightly indented nucleus
 Thin rim of pale blue cytoplasm
1. T lymphocyte (T cells) fight antigens directly
2. B lymphocytes (B cells) divide to produce plasma cells that
secrete antibodies
LYMPHOCYTES
 Function is the synthesis and excretion of
antibodies (immunoglobulins)
 Normally not present in the peripheral blood;
comprise 2% of bone marrow cells.
 May be seen in the peripheral blood in the disease
called multiple myeloma, a disease of uncontrolled
production of immunoglobulins.
 End stage of the B lymphocyte
▪ Size: 10-18µm
▪ Cytoplasm is dark blue with perinuclear halo and
may contain vacuoles indicating antibody
synthesis
▪ Nucleus is round, eccentric, dark purple with
dense clumped chromatin
1. Grape or Mott cell -
cytoplasm completely filled
with red, pink or colorless
globules called Russell
bodies
2. Flame cell - cytoplasm stains
bright red-staining
proteinaceous material
Flame cell
 CFU-Ly divides form the CFU-LyB and CFU-LyT
 CFU-LyB migrate to “bursa-equivalent location”,
divided  B lymphocytes
 CFU-LyT undergo mitosis migrate to the Thymus T
lymphocytes
Monocytes:
 72 hrs in blood.
 Once in tissue they swell up to much larger size to
become tissue macrophage → in this form they can live
for months.
Lymphocytes:
 Life span for week or months depending on body’s need.
 They continually circulate in blood & move from blood to
tissues & from tissues to blood and again blood to tissues.
 The cytokines which control the formation of different
types of granulocytes are called colony stimulating factor
[CSF]
 CSF is a glycoprotein formed by T and B lymphocytes
 Also forms:
 G-CSF: stimulate granulocyte precursors
 M-CSF: stimulate monocytic precursors
 GM-CSF: both granulocytes and monocytic precursors
 The cytokines that control lymphocyte formation
are called interleukins.
- E.g.; IL-1, IL-3 etc….
 The interleukins are formed by MONOCYTES,
MACROPHAGES & ENDOTHELIAL CELLS.
Leucopoiesis

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Leucopoiesis

  • 1. Developed by: Abdelwahab Khalid Ibrahim HONOR DEGREE IN HEMATOLOGY Lecture 5
  • 2.
  • 3.  Def: Formation and maturation of white blood cells.  Granulocytopoiesis  Agranulocytopoiesis –Monocytopoiesis –Lymphoctye maturation
  • 4.  There are 3 different areas in our body where different WBCs reside: 1. Marrow pool: 90% neutrophils 2. Blood pool: 3% 3. Tissue pool: 7%
  • 5.  In bone marrow → PHSC (Pluripotential hemopoietic stem cells) differentiates → committed stem cells → CFU-GM  Granulocytes & monocytes are formed only in bone marrow.  lymphocytes & plasma cells are produced in various lymphogenous tissues
  • 6.
  • 7.  Granulocytes and monocytes are formed from bone marrow, which is derived from CFU-GM(colony forming units of granuloctyes and monocytes)  The progenitor cells [CFU-GM] forming different cells are further named as; - CFU-G= neutrophil forming units - CFU-E= eosinophil forming units - CFU-B= basophil forming units - CFU-M= monocyte forming units
  • 8.  Development of granulocytes-includes various stages called Myeloid series  Development of monocytes –includes various stages called Monocytes-macrophages series
  • 9.
  • 10.  Process of granulopoiesis-12 days  Granulocytes are formed and stored in the bone marrow –when needed it is released in the circulation  Regulated by growth factors, CSF & Interleukins  Granulocyte maturation divide into six stages.  All of the granulocyte derive from myeloblast
  • 11.  Structural Changes during differentiation & maturation: A. A decreased in cell size B. Condensation of nuclear chromatin C. Changes in nuclear shape D. An accumulation of cytoplasmic granule
  • 12.
  • 14.  It is the earliest recognizable cell of the granulocyte series:  Size:16-20um  Cytoplasm: basophilic  Present as thin rim aroundthe Nucleus  Devoid of granules
  • 15. Nucleus: Large nearly filling the cells round to oval, Fine chromatin, 2-5 well defined pale nucleoli Mitosis: marked [+++].
  • 16.  Size: 14-18um  Cytoplasm : increased in amount  Presence of azurophil granules [primary Non specific granules]  Gives +ve reaction with the peroxidase Staining
  • 17.  Nucleus: round or oval  Slightly smaller than myeloblast nucleus condensed fine chromatin  Nucleoli present-less prominent  Mitosis: characteristic feature{+++}
  • 18.
  • 19.  Size: 12-16um  Cytoplasm : specific secondary granules present identified at this stage as; - Neutrophil myelocyte - Eosinophil myelocyte - Basophil myelocyte  Primary granules are also presentat this stage but their formation is stopped
  • 20.  Nucleus: eccentric, round-oval  Coarse nuclear chromatin .  No, nucleoli present  Mitosis: continues up to this stage  Multiplication of these cells are maximum
  • 21.  Size: 10-14um  Cytoplasm: increased in amount - More liquid - Primary and secondary granules are present according to secondary granules it is distinguished as; • Neutrophil metamyelocyte • Eosinophil metamyelocyte • Basophil metamyelocyte
  • 22.  Nucleus: decrease in size  Lobed (horse shoe shaped)  Nuclear chromatin is dense and clumped nucleoli are absent  Mitosis: stopped at this stage.
  • 23.  Also called juvenile granulocytes  Size: smaller than metmyelocytes  Cytoplasm: pink and fine evenly distributed granules  Nucleus: further condensation of chromatin - Shape: band configuration [v shaped] of uniform thickness which may be twisted.
  • 24.
  • 25. - Diameter = 10-12 m - Cytoplasmic granules stain pale lavender - Lobed nuclei (3-5 lobes) - % of total leukocytes: 50-70% - Drumstick: inactive X-chromosome Granules contain lysosomal enzymes and defensins Neutrophils are quick acting phagocytes (1st responders) They are quick but weak! Typical Neutrophil 1. NEUTROPHIL (POLYMORPHONUCLEAR CELL)
  • 26.  Diameter = 10-14 m  Large granules which stain red (major basic protein)  Bilobed nucleus  Represent 2-4% of the total WBC count Granules contains and functions: Granules contain digestive enzymes Are antiparasitic Phagocytize immune complexes Anti-allergy 2. EOSINOPHIL
  • 27.  Diameter = 8-10m  Large granules which stain blue  U or S shaped nucleus  0.5 – 1% of total WBC Granules contain: histamine which induces inflammation and vasodilatation heparin an anticoagulant 3. BASOPHIL
  • 28.
  • 29.  All of the granulocyte derive from myeloblast  Myelocyte is the stage when three types of granulocyte can be recognized  The maturation process of granulocyte characterized by : – synthesis of azurophilic and specific granules – Condensation of nucleus  Mature granulocyte leave the bone marrow then enter the circulation connective tissue
  • 31.  It is the larger cell, similar to myeloblast
  • 32. 1
  • 33.  It is an young monocyte  Size: 20um  Nucleus: larger - Kidney shaped one nucleoli - Nuclear chromatin: arranged in aloose network  Cytoplasm: basophilic - No azurophilic granules -They have fine granules which is larger than mature monocytes
  • 34. 2
  • 35. Are phagocytes – slow but strong Develop into macrophages when they migrate into connective tissue 3. MONOCYTES Diameter = 18 m Nucleus is U shaped or kidney shaped Abundant pale blue cytoplasm 3 – 8 % of the total WBC
  • 36.  Once the monocyte enters the tissues, it becomes a macrophage  Size:15-80µm  Cytoplasm ▪ Gray-blue and abundant ▪ Ragged edges ▪ Vacuoles common Nucleus Round with netlike appearance Purplish with finer clumped chromatin  Nucleoli appear
  • 37.
  • 38.
  • 39.
  • 41.  Cell size: 10-20µm  Cytoplasm ▪ Blue/scanty ▪ No granules, Auer rods are never present  Nucleus ▪ Purple, smooth chromatin ▪ Round, central or eccentric ▪ 1-2 nucleoli  N:C ratio = 4:1
  • 42.  Size: 9-18µm  Cytoplasm ▪ Blue, scanty ▪ Usually granules are absent, but a few azurophilic granules may be present  Nucleus ▪ Purple, condensed chromatin ▪ Round or indented, eccentric ▪ 0-1 nucleoli  N:C ratio = 4:1
  • 43.  LYMPHOCYTES T-LYMPHOCYTES  LYMPHOCYTES B-LYMPHOCYTES  LYMPHOCYTES B-LYMPHOCYTES Thymus Liver Bone
  • 44.  Diameter 5-8 m (small), 10-12 m (medium) or 14-17 m (large)  20-25 % of the total WBC count  Large, deep blue or slightly indented nucleus  Thin rim of pale blue cytoplasm 1. T lymphocyte (T cells) fight antigens directly 2. B lymphocytes (B cells) divide to produce plasma cells that secrete antibodies LYMPHOCYTES
  • 45.  Function is the synthesis and excretion of antibodies (immunoglobulins)  Normally not present in the peripheral blood; comprise 2% of bone marrow cells.  May be seen in the peripheral blood in the disease called multiple myeloma, a disease of uncontrolled production of immunoglobulins.  End stage of the B lymphocyte
  • 46. ▪ Size: 10-18µm ▪ Cytoplasm is dark blue with perinuclear halo and may contain vacuoles indicating antibody synthesis ▪ Nucleus is round, eccentric, dark purple with dense clumped chromatin
  • 47. 1. Grape or Mott cell - cytoplasm completely filled with red, pink or colorless globules called Russell bodies 2. Flame cell - cytoplasm stains bright red-staining proteinaceous material Flame cell
  • 48.  CFU-Ly divides form the CFU-LyB and CFU-LyT  CFU-LyB migrate to “bursa-equivalent location”, divided  B lymphocytes  CFU-LyT undergo mitosis migrate to the Thymus T lymphocytes
  • 49. Monocytes:  72 hrs in blood.  Once in tissue they swell up to much larger size to become tissue macrophage → in this form they can live for months. Lymphocytes:  Life span for week or months depending on body’s need.  They continually circulate in blood & move from blood to tissues & from tissues to blood and again blood to tissues.
  • 50.
  • 51.  The cytokines which control the formation of different types of granulocytes are called colony stimulating factor [CSF]  CSF is a glycoprotein formed by T and B lymphocytes  Also forms:  G-CSF: stimulate granulocyte precursors  M-CSF: stimulate monocytic precursors  GM-CSF: both granulocytes and monocytic precursors
  • 52.  The cytokines that control lymphocyte formation are called interleukins. - E.g.; IL-1, IL-3 etc….  The interleukins are formed by MONOCYTES, MACROPHAGES & ENDOTHELIAL CELLS.