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m02 Hematopoiesis 1 2
m02 Hematopoiesis 1 2
m02 Hematopoiesis 1 2
HEMATOPOIESIS
UNIT 1: INTRODUCTION TO HEMATOPOIESIS
At the end of the module, students should be able to:
1. Discuss the maturation sequence of blood cells from embryo to fetus to adult.
2. Differentiate immature from mature blood cells.
3. Describe the microscopic presentation of the different blood cells.
4. Discuss the roles of hematopoietic growth factors in blood cell production.
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PHASES OF HEMATOPOIESIS (Fig. 2-3)
Hematopoiesis is generally categorized as primitive or definitive. Primitive
hematopoiesis occurs in the embryo during the first two weeks and lasts up to the
eighth week of gestation. It is the time when the blood cells produced are mostly
primitive erythrocytes. Definitive hematopoiesis occurs on the eighth week until
adulthood. In this stage, different blood cells are produced which can be distinguished
morphologically and functionally thus the term definitive.
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2. Hepatic Phase
Begins at around 5-7 gestational weeks
PRIMARY SITE/S OF HEMATOPOIESIS: FETAL LIVER
1. Liver
Becomes the primary site of hematopoiesis during the 3rd month of
fetal development
Retains minimal activity up to 1-2 weeks after birth
2. Thymus
First fully developed organ in the fetus
Becomes the major site of T cell production
3. Spleen & Kidneys
Production of B lymphocytes
Spleen gradually decreases granulocytic production and involves itself
solely in lymphopoiesis
4. Lymph nodes
BLOOD CELL/S FORMED:
Erythrocytes still in production
Granulocytes & Megakaryocytes (3rd month of gestation)
Lymphocytes (4th month of gestation)
Monocytes (5th month of gestation)
FETAL HEMOGLOBIN (4th month of gestation) is the PREDOMINANT
HEMOGLOBIN but detectable levels of adult hemoglobin may be present
i. HbF: 2 alpha & 2 gamma chains
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3. Myeloid Phase
Begins prior to the 5th month of development
PRIMARY SITE/S OF HEMATOPOIESIS: BONE MARROW (end of 6th month)
i. “Medullary hematopoiesis”: Hematopoiesis occurs inside the medulla of
the bone (where the bone marrow is located) (Fig. 2-4).
In the space provided, illustrate the cross-section of a long bone and label the parts. Take
note of the location of the medullary cavity. (See Keohane, Smith, and Walenga, 2016
for reference.)
ii. At birth, bone marrow becomes the ONLY SITE FOR PRODUCTION of
erythrocytes, granulocytes, monocytes, platelets, and B lymphocytes
Myeloid-to-erythroid ratio gradually approaches 3:1 (adult levels)
Measurable levels of Hemoglobins F and A
i. HbA : 2 alpha chains & 2 beta chains
ii. HbA2: 2 alpha chains & 2 delta chains
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Figure 2-5. Myeloid Hematopoiesis
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Figure 2-5 shows that during infancy and early childhood; all bones in the body contain
the red marrow. By age 5 to 7, retrogression occurs. This is the process of replacing the
haematopoietically active red marrow with yellow marrow. The yellow marrow is consisting
of adipocytes that is capable of reverting back to active marrow in cases of increased
demand for blood cell production in the body.
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Structure of the BM (Fig. 2-6):
A. Vascular region: Vascular sinuses
Vascular sinuses (specialized blood vessels)
B. Hematopoietic cords
These are extravascular cords that are composed of hematopoietic cells
and macrophages. They are located in spaces between the vascular
sinuses and are supported by trabeculae of spongy bone. It is noted that
hematopoietic cells develop in specific niches within the cords.
Niches/ Hematopoietic
Microenvironment (within the
cord) play a very important role
in nurturing and protecting
hematopoietic stem cells
Erythroblast:
Develop in small
clusters; More mature
forms located in outer
surfaces of the vascular
sinuses
Found surrounding
iron- laden
macrophages
Megakaryocytes: Adjacent to
the walls of vascular sinuses
Immature myeloid cells (up to
metamyelocyte stage): Deep
within the cords (as the
Figure 2-6. Cross-section of bone with active marrow mature, they move closer to
the vascular sinuses)
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ENTRY OF MATURE BLOOD CELLS FROM THE BONE MARROW TO PERIPHERAL CIRCULATION
Mature blood cell Adventitial cell layer (contracts) Basement membrane Endothelial
cell layer Receptor-mediated process Mature cells bind to the surface of
endothelial cells Cells pass through pores in the endothelial cytoplasm Vascular sinus
Peripheral circulation
Collection
1. Trephine/ Core biopsy
Utilizes Trephine biopsy needle (Jamshidi needle)
2. Aspiration
Aspiration needle (University of Illinois sternal needle)
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Normal: 2:1 to 4:1 (Average of 3:1)
Infection: 6:1
Leukemia: 25:1
Normal marrow cells
a. All developing hematopoietic cells
b. Macrophages
c. Mast cells
d. Osteoblasts
Waterbug or comet appearance
Confused with plasma cells
e. Osteoclasts
Misidentified as megakaryocytes
2. THYMUS
Figure 2-8. The anatomy (left) and histology (right) of the thymus.
The thymus is a small, flat bilobed organ (Fig. 2-8, left) found in the thorax that has
an average 30g weight at birth, 35 g weight at puberty and gradually atrophies.
It is where T-cell maturation happens.
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Dendritic cells are derived from the monocytes. They exhibit
long dendrite-like projections and assist the maturation process of the
pre-T cells.
Epithelial cells are specialized to carry out the positive selection
process of pre-T cells. They have long processes that serves as a
framework for the T cells and produce thymic hormones that are
thought to aid in the maturation of T cells
The thymic macrophages help clear out the debris of dead
and dying cells.
Medulla
The medulla is the inner part of the thymic lobule. It consists of
more mature T cells, dendritic cells, and epithelial cells, and
macrophages.
In the medulla are* Thymic (Hassall’s) corpuscles which are
clusters of epithelial cells that become arranged into concentric layers
of flat cells that degenerate & become filled with keratohyalin granules
and keratin.
1. Lymph Nodes
Lymph nodes (Fig. 2-9) are bean-shaped structures found along lymphatic
vessels which are specialized to filter lymph flowing through the lymphatic
vessels.
Medulla
The medulla is less densely populated and contains T cells, B cells,
macrophages, and numerous plasma cells.
2. Spleen
The spleen is the largest secondary lymphoid organs that functions as a large
discriminating filter. It removes damaged cells and foreign antigens from the blood.
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- Parts of the Spleen (Fig. 2-11)
Stroma
The stoma consists of capsule, trabeculae, reticular fibers and
fibroblasts.
Parenchyma
The parenchyma is the functional part of the spleen. It consists of two
different kinds of tissue. The white pulp is approximately 20% of the
weight of the spleen and consists of lymphoid tissues. The structures of
the white pulp are the following:
i. Periarteriolar lymphoid sheath (PALS)
- Contains mainly T cells
ii. Primary follicles
- Contains B cells that are not yet introduced and
stimulated by the antigen
iii. Marginal Zones
- Surrounds the primary follicles
- Contains dendritic cell that traps antigens
iv. Germinal Centers in secondary follicles
- Site of blast transformation of B cells
- Site of formation of plasma cells and B memory
cells The red pulp makes up more than one half of the volume of
the spleen. It has the following parts:
i. Venous sinuses
- Blood-filled structures
ii. Splenic (Billroth’s) Cords
- Cords of splenic tissue
- Consists mainly of:
Red blood cells
Macrophages
Lymphocytes
Plasma cells
Granulocytes
3. Lymphatic nodules
The lymphatic nodules are egg-shaped masses of lymphatic tissue that resembles
lymph nodes but do NOT have capsules. They may be present in:
Small, solitary form
i. Mucosa associated lymphoid tissue
- Scattered in the lamina propria of the mucosa of the gastrointestinal,
urinary and the reproductive tracts
ii. Cutaneous associated lymphoid tissue
- Intraepidermal lymphocytes (mostly T cells)
Multiple, aggregated form
i. Tonsils
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ii. Peyer’s patches
- Aggregated lymphatic follicles in the ileum of the small intestine
STEM CELLS
Stem cells are undifferentiated/ slightly differentiated cells that may either self-
renew or give rise to cells of different lineages
- Types:
a. Totipotential stem cell that can differentiate into all possible cells of the
organism, including the extra-embryonic membranes
b. Pluripotential stem cell that can give rise to all of the cells of the embryo, and
therefore of a whole animal, but are no longer capable of giving rise to extra-
embryonic structures
c. Multipotential stem cell that can give rise to multiple lineages but has lost the
ability to give rise to all body cells
HEMATOPOIETIC STEM CELL THEORY
1. Monophyletic theory
The monophyletic theory states that blood cells are derived from a single
progenitor cell (Pluripotent hematopoietic stem cell. It is the most widely
accepted theory
2. Polyphyletic theory
It states that each blood cell lineages are derived from own unique stem cell.
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Mitosis
Nuclear division
Distribution of two sets of chromosomes into separate
nuclei Prophase Chromatin fibers condense into paired
chromatids
Nucleolus and nuclear envelope disappear
Each centrosome moves to an opposite pole of the cell
Metaphase Centromeres of chromatid pairs line up at the metaphase plate
Anaphase Centromeres split
Identical sets of chromosomes move to opposite poles of
cell Telophase Nuclear envelopes and nucleoli reappear
Chromosome resume chromatin form
Mitotic spindle disappears
Cytokinesis
Cytoplasmic division
Usually begins in late anaphase with the formation of a cleavage furrow & is
completed after the telophase
After completing the cell cycle, the stem cells have the following possible fates:
1. Apoptosis
Programmed cell death
2. Self-renewal
Returning of daughter cell to stem cell pool
3. Differentiation
Stem cells differentiate to acquire new morphologic features and give rise to
more mature forms
Types of Division
1. Symmetric division
Both daughter cells follow the path of differentiation
2. Asymmetric division
One daughter cell returns to stem cell pool while the other differentiates
Development
1. Synchronous development
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Cytoplasm and nucleus mature at the same rate
2. Asynchronous development
Cytoplasm or nucleus mature first before the other
Can lead to abnormality in shape and size
Cell Maturation
1. Blast cells do not have granules
2. Blast cells contain a large nucleus (3/3 to 7/8 of cell area) and a small amount
of cytoplasm
3. As cells mature, the cytoplasm becomes less basophilic (Exception: Plasma cell)
4. As cells mature, the chromatin of the nucleus becomes heavier, and the darker the
nucleus stains the heavier the chromatin is
5. As the cells mature, they become smaller (Exception: Megakaryocyte)
6. Nucleoli tend to disappear in mature cells
7. As cells mature, specific granules become less prominent and smaller
8. There are four different types of granules: neutrophilic, basophilic, eosinophilic, and
azurophilic (primary).
Cytokines
Cytokines are group of specific glycoproteins secreted by cells. In hematopoiesis,
they regulate the proliferation, differentiation, and maturation of hematopoietic
precursor cells. These include interleukins, lymphokines, monokines, interferons,
chemokines, and colony-stimulating factors (CSF).
Interleukins
Interleukins are cytokines with multiple actions and are numbered by
scientists in the order in which they were identified.
Characteristics:
a. They are proteins that exhibit multiple biologic activities, such as regulation
of autoimmune and inflammatory reactions and hematopoiesis
b. They have synergistic interactions with other cytokines.
c. They are part of interacting systems with amplification potential.
d. They are effective at very low concentrations
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GM-CSF (Granulocyte-Macrophage Colony-stimulating Factor)
Stimulates the proliferation of the granulocytic-monocytic cell
line
Also works synergistically with Interleukin-3 (IL-3) to
enhance megakaryocyte colony formation
iii. GM-CSF
Induces expression of specific genes that stimulate
hematopoietic stem cell differentiation to the common myeloid
progenitor.
iv. Interleukin-3 (IL-3)
Aka Multi-CSF
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Figure 2-11. DERIVATION OF BLOOD CELLS FROM HEMATOPOIETIC STEM CELLS
(Source: Henry’s Clinical Diagnosis and Management by Laboratory Methods, 22nd Edition)
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UNIT 2: ERYTHROPOIESIS
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EXPLAIN
4. NUCLEAR CHANGES
5. CYTOPLASMIC CHANGES
6. CELL SIZE
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Erythropoietin (EPO)
EPO is the glycoprotein hormone produced by the kidneys (renal peritubular
interstitial cells). Its main effect is to place more erythrocytes into circulation at a
faster rate by:
o Early release of reticulocytes
o Prevent apoptotic cell death
o Reduces maturation time inside bone marrow
Maturation sequence
I. Erythroid Progenitors
a. Pluripotential hematopoietic stem cell
b. CFU-GEMM/ CFU-S
c. CFU-MegE
d. *BFU-E (Particularly produced under increased demand for RBCs/ pathologic
erythropoiesis)
e. CFU-E
II. Erythroid Precursors
a. Pronormoblast
b. Basophilic normoblast
c. Polychromatic (polychromatophilic) normoblast
d. Orthochromic normoblast
e. Reticulocyte/ Polychromatic (polychromatophilic) erythrocyte
f. Erythrocyte
Approximately 18 TO 21 DAYS are required to produce a mature RBC from the BFU-E
o 1 week for BFU-E to mature to CFU-E
o Another 1 week for CFU-E to mature to pronormoblast
o Another 6-7 days for the precursors to mature enough to enter the circulation
o 8 to 32 mature RBCs usually result from a single pronormoblast
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Erythroid Precursors - Keohane, Smith and Walenga, 2016
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Figure 2-13. Red blood cell maturation sequence
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UNIT 3: ERYTHROCYTE KINETICS
The red cell membrane can be divided into two parts – the lipid bilayer and the membrane
proteins. The lipid bilayer consists of two back-to-back layers made up of three types of
lipid molecules:
i. Phospholipids (75%)
Phospholipids are amphipathic lipids – they have both polar and
nonpolar parts. The polar part is the phosphate-containing “head”
and the nonpolar part has two long fatty acid “tails”. They can be
asymmetrically divided:
Outer layer: Phosphatidylcholine & Sphingomyelin
Inner layer: Phosphatidylserine
& Phosphatidylethanolamine
ii. Cholesterol (20%)
It is a steroid with an attached hydroxyl group, weakly amphipathic
and are interspersed among the other lipids in both layers of the
membrane. The polar part contains the hydroxyl group and the non-polar
part contains the steroid rings and hydrocarbon tail.
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iii. Glycolipids (5%)
Glycolipids are lipids with attached carbohydrate groups that
appear only in the membrane layer that faces the extracellular
fluid. It is one of the reasons the two sides of the bilayer are
asymmetrical. The polar part contains the carbohydrate “Head”
and the nonpolar part contains the fatty Acid “Tail”.
The membrane proteins are of two (2) types. The peripheral proteins which are not
firmly attached in the membrane but rather attached to the polar heads of
membrane lipids and the integral proteins which are firmly attached to the bilayer
membrane and extend into or through the lipid bilayer among the fatty acids.
RBC METABOLISM
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- For each mole of glucose, a total of 4 ATP molecules are
produced. However, for anaerobic glycolysis to occur, 2 moles
of ATP must be consumed resulting in a net gain of 2 ATP
moles
RBC DESTRUCTION
Due to natural catabolism, red blood cells will eventually experience deterioration
of their enzymes. As nonnucleated cells, the mature RBCs are unable to generate or
replenish enzymes including glycolytic enzymes that lead to senescence/ aging of
red blood cells. CULLING is the destruction of senescent (aged) red blood cells by
the spleen.
Mechanisms:
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ACTIVITY 3 (Erythrocyte kinetics): Discuss
what happens to the red cell in each of the
given scenario: (3 points each)
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UNIT 4: LEUKOPOIESIS
Leukocytes are a heterogenous group that can be divided into two – the
granulocytes and agranulocytes. The granulocytes together with the monocytes share the
same lineage with the red cells (CFU-GEMM) while the lymphocytes have their own (CFU-
L).
A. GRANULOPOIESIS
Granulopoiesis pertains to the production and development of the three
granulocytes – the neutrophils, eosinophils and basophils. The maturation sequence is
almost similar for the three types of cells, except for the cytokines that influence
production and differentiation.
1. Neutrophil Development
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Table 2-1. Characteristics of cells in the maturation sequence of granulocytes
Cell/ Stage Size N:C Nucleus Cytoplasm Cellular Activity
(um) ratio Shape Chromatin Nucle Staining Granules
oli
MYELOBLAST 14- 8:1 to Round Homogenous, 2 to 4 Slightly No Granules 0-3% of nucleated
20 4:1 to oval delicate, fine basophili cells in BM
euchromatin c * Classification:
Type I blasts:
No visible
granules
“Granular blasts”
Rare in normal
marrow
Type II blasts: < 20
visible primary or
azurophilic
granules
Formation of
SECRETORY
GRANULES
(vesicles)
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Neutrophil Granules
Primary (Azurophilic) Granules
Formed during the promyelocyte stage
Last to be released (Exocytosis)
Contain:
Myeloperoxidase
Acid-β- glycerophosphate
Cathepsins
Defensins
Elastase
Proteinase-3
Others
Secondary (Specific) Granules
Formed during myelocyte and metamyelocyte stages
Third to be released
Contain:
β2- microglobulin
Collagenase
Gelatinase
Lactoferrin
Neutrophil gelatinase- associated lipocalin
Transcobalamin I
Others
Tertiary Granules
Formed during metamyelocyte and band stages
Second to be released
Contain:
β2- microglobulin
Collagenase
Gelatinase
Lysozyme
Acetyltransferase
Secretory Granules (Secretory Vesicles)
Formed during the band and segmented neutrophil stages
First to be released (fuse to plasma membrane)
Contain (attached to the membrane):
CD11b/ CD18
Alkaline phosphatase
Vesicle-associated membrane-2
CD10, CD13, CD14, CD16
Cytochrome b558
Complement 1q receptor
Complement receptor-1
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- Normal values:
o Bone marrow: 7-30% of nucleated cell population
o Relative value in peripheral blood: 50-70% of WBCs
o Absolute value: 1.7-7.5 x 109/ L
- Neutrophil kinetics:
o Production: 0.9-1.0 x 109 cells/ kg per day
o Mitotic pool: 2.11 x 109 cells/ kg
o Maturation pool: 5.6 x 109 cells/ kg
o Once in the peripheral blood, neutrophils are divided randomly into a
circulating neutrophil pool (CNP) and a marginated neutrophil pool (MNP).
The ratio of CNP and MNP is roughly equal.
o Majority of the MNP are in the capillaries of the lungs.
- Transit time:
o HSC to myeloblast: 6 days
o Myeloblast to maturation pool: 4 to 6 days
o Neutrophil half-life in blood: 6-8 hours
o It takes about 14 days from the blast stage to the release of
mature granulocytes.
Neutrophil Function:
a. Phagocytosis
Digestion:
Oxygen dependent
Respiratory burst through the activation of NADPH oxidase. H2O2
and peroxidase are produced
Oxygen independent
The pH within the phagosome becomes alkaline and then
neutral, the pH at which digestive enzymes work.
b. Generation of neutrophil extracellular traps (NETs)
o NETs
Nuclear & organelle membrane dissolves DNA release DNA +
cytoplasmic enzymes Cell membrane ruptures NET release
Extracellular threadlike structures believed to represent chains
of nucleosomes from DNA
Have enzymes from neutrophil granules
Have been shown to be able to trap and kill gram-positive and gram-
negative bacteria as well as fungi
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“NETosis”: NETs are generated at the time that neutrophils die as a result of
o
antibacterial activity
c. Secretory Function
Transcobalamin I/R binder (needed for Vitamin B12 absorption)
Variety of cytokines
2. Eosinophil Development
Maturation Sequence
I. Pluripotential hematopoietic stem cell
II. Progenitors:
a. CFU-GEMM (Common Myeloid Progenitor)
b. CFU-Eo
III. Precursors:
a. Myeloblast
b. Promyelocytes
c. Myelocytes
d. Metamyelocytes
e. Eosinophilic band
IV. Eosinophil
Precursors:
A. Eosinophilic myeloblasts
o Not fully characterized
B. Promyelocytes
o Cytochemical identification only
o PRIMARY GRANULE: Charcot-Leyden crystal protein
C. Myelocytes
o Similar to neutrophil myelocytes
o Large, pale, reddish-orange SECONDARY GRANULES
D. Metamyelocytes & Band Forms
o Resemble their neutrophil counterpart
o Formation of SECRETORY GRANULE/ VESICLE
o Two other organelles are also present: Lipid bodies and Small lysosomal
granules
Eosinophil Granules
Primary Granules
Formed during the promyelocyte stage
Contain:
Charcot-Leyden crystals
Secondary (Specific) Granules
Formed throughout remaining maturation stages
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Contain:
Major basic protein (core)
Eosinophil cationic protein (matrix)
Eosinophil- derived neurotoxin (matrix)
Eosinophil peroxidase (matrix)
Lysozyme (matrix)
Catalase (core and matrix)
β-Glucuronidase (core and matrix)
Cathepsin D (core and matrix)
Interleukins 2,4, and 5 (core)
Interleukin- 6 (matrix)
Granulocyte- and Macrophage colony-
stimulating factor (core)
Others
Small Lysosomal Granules
Acid phosphatase
Arylsulfatase B
Catalase
Cytochrome b558
Elastase
Eosinophil cationic protein
Lipid Bodies
Cyclooxygenase
5-Lipoxygenase
15-Lipoxygenase
Leukotriene C4 synthase
Eosinophil peroxidase
Esterase
Storage Vesicles
Carry proteins from secondary granules to be released into
the extracellular medium
Eosinophils have bilobed nucleus measuring around 9-15 microns. They possess
refractile, orange-red granules and are involved in allergic and parasitic infections.
Eosinophils are further characterized by the following:
- Normal values:
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o Relative value: 1-3% of WBC in peripheral blood
o Absolute value: 0-0.3 x 109/ L
- Production of eosinophil from last myelocyte division: 3.5 days
- Eosinophil kinetics:
o Turnover of eosinophils: 2.2 x 108 cells/ kg
o Large storage pool: 9-14 x 108 cells/ kg
o Half-life in circulation: 18 hours
o Survival in tissues: 2-5 days (columnar epithelial cells of the respiratory,
genitourinary, and gastrointestinal tracts)
Eosinophil Function:
a. Eosinophil degranulation
i. Classical exocytosis
Granules move to plasma membrane Fuse with cell membrane
Emptying of contents to extracellular fluid (ECF)
ii. Compound exocytosis
Granules fuse together within eosinophils Fuses with cell membrane
Emptying to ECF
iii. Piecemeal degranulation
Secretory vesicles remove specific CHONs from 20 granules
Secretory vesicles migrate to plasma membrane Emptying to ECF
Maturation Sequence:
I. Pluripotential hematopoietic stem cell
II. Progenitors:
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a. CFU-GEMM (CMP)
b. CFU-Baso
III. Immature basophil
IV. Mature basophil
Basophil Granules
- Normal values
Relative value: 0-2%
Absolute value: 0-0.2 x 109/ L
- Basophil kinetics:
Poorly understood
Life span of 60 hours
- Basophil functions: (ALLERGIC OR HYPERSENSITIVITY REACTION)
Basophils possess surface IgE receptors. They regulate Th2 response (IL-4 & IL-
3), induce B cells to synthesize IgE, mediate allergic processes (production of
HISTAMINE, Granzymes B, retinoic acid) and promote angiogenesis (Vascular
endothelial growth factor production)
Mast cells are erroneously called tissue basophils. They are not true leukocytes; they are cells
from the BM that uses blood as transit system to gain access to tissues where they mature.
They function as effector cells in allergic reactions by stimulating IgE receptors and
inflammatory reactions by an IgE receptor-independent process. They can also act as antigen
presenting cells that induce Th2 differentiation. They are known for their anti-inflammatory
and
B. AGRANULOPOIESIS immunosuppressive functions.
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1. MONOPOIESIS
Maturation sequence (Table 2-2):
I. Pluripotential hematopoietic stem cell
II. Progenitors:
a. CFU-GEMM (CMP)
b. CFU-GM
c. CFU-M
III. Precursors:
a. Monoblasts
b. Promonocyte
IV. Monocyte
V. Tissue spaces: Macrophage
Macrophages are large cells ranging from 40-50 microns. They present with
oval, reticulated chromatin nucleus and a pale, frequently vacuolated cytoplasm. They are
either wandering, or fixed as to location. They are given names according to their tissue
location:
Liver: Kupffer cells
Lungs: Alveolar macrophages
Brain: Microglia
Skin: Langerhans cells
Spleen: Splenic macrophages
Bone: Osteoclasts
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Synovial membrane: Type A cell
Kidneys: Mesangial cells
Lymph nodes: Dendritic cells
2. LYMPHOPOIESIS
Table 2-3. Characteristics of cells in the maturation sequence of lymphocytes
Stage Cell Size (microns) Nucleus Cytoplasm
LYMPHOBLAST 10-18 Coarse chromatin No granules present
Round or oval Appears smooth
With 1-2 nucleoli Moderate to dark
blue
PROLYMPHOCYTE Maybe same size as More clumped Usually nongranular
lymphoblast or chromatin Moderate to dark
smaller Round or oval in shape blue
With 1- 2 nucleoli
MATURE LYMPHOCYTE
SMALL LYMPHOCYTE 8-10 Dense chromatin Very scanty
Round or oval in shape ROBIN’S EGG BLUE
No nucleoli visible
OCCUPIES MAJORITY
OF CELL AREA
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Functionally, lymphocytes are classified into three. T lymphocytes which are
responsible for cellular-mediated immunity comprise 60 to 80% of the lymphocyte
population and last for 4 to 10 years. B lymphocytes which are involved in humoral-
mediated immunity comprise about 10 to 20% of the lymphocyte population and last for
3 to 4 years. Null lymphocytes which are capable of tumor host defense comprise only
10% of the lymphocytes in the body.
Lymphocytes have a relative value of 18-42% and an absolute value of 1- 3.2 x 109/ L.
a. CD4+/ Thelper
o Th1: Against intracellular pathogens
o Th2: Against extracellular parasites; Induction of asthma and allergic diseases
o Th17: Against extracellular bacteria and fungi
b. CD8+/ Tcytotoxic
o Secretes granules containing granzymes and perforins
o Killing of target cells
c. Treg
o Regulate immune response
o Maintains self-tolerance
d. B lymphocytes
o Antibody production (Plasma cell)
o Antigen presentation to T cells
Optimal CD4+ activation
o Production of cytokines (Regulates T cell and antigen presentation)
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SAINT LOUIS UNIVERSITY
SCHOOL OF NATURAL SCIENCES
DEPARTMENT OF MEDICAL LABORATORY SCIENCE
Name: _
Instructor:
Rating:
Date:
EXPERIMENT 3
HEMATOPOIESIS
OBJECTIVES
MATERIALS
Hematology atlas
Charts
PROCEDURE
1. Listen very carefully as the instructor discusses the different stages in the development of
the cellular components of the blood.
2. Using hematology atlases and charts, trace the different stages in the development of each
series. Take note of the characteristics of the different cells.
DRAWINGS
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11. The best source of active bone marrow from a 25-year-old male patient would be:
A. Iliac crest B. Femur C. Distal radius D. Tibia
13. A. In the red cell maturation sequence, the acidophilic erythroblast is the last cell
capable of mitosis.
B. It is also in this stage that the highly-condensed nucleus is ejected.
B. MATCHING TYPE. Match the following Growth Factors with their Primary Target (10
POINTS)
1. G-CSF - D A. Basophils
2. Il-5 - G B. Megakaryocytes
4. IL-6 - I D. Neutrophils
6. TPO - B F. Monocytes
7. Kit-Ligand - E G. T-cells
8. IL-9 – G H. Adipocytes
10.EPO - C J. Macrocytes
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