◆ Liver

COURSE OUTLINE ◆ Spleen

◆ Bone marrow and lymph nodes
I. HEMATOPOIESIS ➔ Can also be by phases
A. MESOBLASTIC PHASE 1. Mesoblastic
B. HEPATIC PHASE 2. Hepatic
C. MEDULLARY (MYELOID) PHASE 3. Myeloid
II. STEM CELL THEORY A. MESOBLASTIC PHASE
A. MONOPHYLETIC THEORY ● Hematopoiesis is considered to begin around the
B. POLYPHYLETIC THEORY nineteenth day of embryonic development after
III. ERYTHROPOIESIS fertilization
IV. RED BLOOD CELL ● Early in embryonic development, cells from the
mesoderm migrate to the yolk sac
● Some of these cells form a primitive erythroblast in
the central cavity of the yolk sac, and others like the
angioblast surround the cavity of the yolk sac.
LEARNING OBJECTIVES
Eventually, form the blood vessels
● Define hematopoiesis ● These primitive but transient yolk sac erythroblasts
● Identify hematopoietic sites are important in early embryogenesis to produce
● Define and Identify the Progenitor Cells hemoglobin (Gower-1, Gower-2, and Portland)
● Discuss the synthesis of RBC needed for delivery of oxygen to rapidly developing
● Discuss the synthesis of WBC embryonic tissues
● Yolk sac hematopoiesis differs from hematopoiesis
I. HEMATOPOIESIS that occurs later in the fetus and adult in that it occurs
● The continuous, regulated process of renewal, intravascularly (or within developing blood vessels)
proliferation, differentiation, and maturation of all
blood cell lines B. HEPATIC PHASE
● These processes result in the formation, ● Begins at 5 to 7 gestational weeks and is
development, and specialization of all the functional characterized by recognizable clusters of developing
blood cells, the release from the bone marrow into the erythroblasts, granulocytes, and monocytes
circulation colonizing the fetal liver, thymus, spleen, placenta,
● Because of mature blood cells lines have a limited life and ultimately the bone marrow space in the final
span and the cell population must be capable of medullary phase
self-renewal that sustains the system ○ The developing erythroblast signal the
beginning of a definitive hematopoiesis with
a decline in the primitive hematopoiesis of
the yolk sac
○ In addition, the lymphoid cells now begin to
appear
● Hematopoiesis during this phase occurs
extravascularly, with the liver remaining the major
site of hematopoiesis during the second trimester of
fetal life
○ Hematopoiesis in this region in the yolk sac
disappear during this stage, hematopoiesis
in the fetal liver reaches its peak with the
third month of fetal development and
gradually declines after the sixth month
pertaining minimal activity and through one
to two weeks after birth
○ The developing spleen, kidney, thymus, and
lymph nodes contribute to the hematopoietic
process during this phase
Figure 1.1 Sites of Hematopoiesis by Age ● The thymus, the first fully developed organ in the
fetus, becomes the major site of T cell production,
whereas the kidney and spleen produce B cells
➔ The y-axis represents the cellularity, and the x-axis
represents the age
➔ There 3 sites of hematopoiesis in the fetal months
◆ Yolk sac
 C. MEDULLARY (MYELOID) PHASE
● Hematopoiesis now occurs in the bone marrow,
termed the medullary hematopoiesis because it
occurs in the medulla or inner part of the bone cavity
● Begins between the fourth and fifth month of fetal
development
● Hematopoietic activity, especially myeloid activity, is
apparent during this stage of development, and the
myeloid-to-erythroid ratio gradually approaches 3:1 to
4:1 (normal adult levels)
● By the end of 24 weeks’ gestation, the bone marrow
becomes the primary site of hematopoiesis

HEMATOPOIESIS
● In adults, hematopoietic tissue is located in the bone
marrow, lymph nodes, spleen, liver, and thymus.
● The bone marrow contains developing erythroid,
myeloid, megakaryocytic, and lymphoid cells
● Lymphoid development occurs in both primary and
secondary lymphoid tissue.
○ The primary lymphoid tissue consist the
bone marrow, thymus, and its where the T
and B lymphocytes are derived
○ The secondary lymphoid tissue where
lymphoid cells respond to foreign antigens,
consist of the spleen, lymph nodes, and the
mucosa associated lymphoid tissue
II. STEM CELL THEORY
● Originally there were two theories describing the
origin of hematopoietic progenitor cells.
● The morphologically unrecognizable hematopoietic
progenitor cells can be divided into 2 major types
○ The noncommitted or undifferentiated
hematopoietic stem cells
○ The committed progenitor cells
○ These 2 groups give rise to all of the mature
blood cells
○ Originally, there were 2 theories describing
the origin of the hematopoietic stem cells or
progenitor cells
A. MONOPHYLETIC THEORY
● The monophyletic theory suggests that all blood
cells are derived from a single progenitory stem cell
called a pluripotent hematopoietic stem cell
B. POLYPHYLETIC THEORY
● The polyphyletic theory suggests that each of the
blood cell lineages is derived from its own unique
stem cell.
The monophyletic theory is the most widely accepted theory
among experimental hematologists
Figure 2.1 Diagram of Hematopoiesis. Note the derivation
of cells from the pluripotent hematopoietic stem cell
➔ Diagram above shows the phases or the flow chart
from the hematopoietic stem cell down to each
corresponding products
➔ Starting from the top: stem cell
➔ Second row: pluripotent hematopoietic stem cell
➔ Pluripotent hematopoietic stem cell differentiate into
common myeloid progenitor and common lymphoid
progenitor
COMMON MYELOID PROGENITOR
● GMP = Granulocyte-monocyte progenitor
● Eosinophil-basophil progenitor
● Megakaryocyte-erythrocyte progenitor
COMMON LYMPHOID PROGENITOR
● Dendritic cell
● Pre-B
● Pre-T
● Natural killer cell
III. ERYTHROPOIESIS
● Erythropoiesis occurs in the bone marrow and is a
complex, regulated process for maintaining adequate
numbers of erythrocytes in the peripheral blood
● The CFU-GEMM gives rise to the earliest identifiable
colony of RBCs called the Burst forming unit -
Erythroid (BFU-E)
○ BFU-E contain only a few receptors for EPO
or also known Erythropoietin
○ There cell cycle activity is not influenced
significantly by the presence of exogenous
EPO
● The BFU-Es under the influence of Interleukin 3
(IL-3), Granulocyte-macrophage colony-stimulating
factor (GM-CSF), TPO, and KIT ligand develop into
colony-forming unit-erythroid (CFU-E) colonies.
○ The CFU-E has many EPO receptors and
has an absolute requirement for EPO.
○ Some CFU-Es are responsive to low levels
of EPO and do not have the proliferative
capacity of the BFU-E.
○ Because EPO serves as a differentiation
factor that causes the CFU-E to differentiate
into pronormoblasts, the earliest visually
 recognized erythrocyte precursors in the
bone marrow.
● Erythroid Progenitors - the morphologically
identifiable erythrocyte precursor developed from 2
progenitors
○ Burst forming unit - Erythroid (BFU-E)
○ Colony forming unit - Erythroid (CFU-E)
➔ Both committed to erythroid cell line
➔ These erythroid progenitors are named for
their ability to form colonies on semisolid
media.
➔ In culture experiments that enable to study
characteristics and development
➔ The earliest committed progenitor the BFU-E
gives rise to the largest colonies because
they are capable of multisub-unit colonies
called burst
➔ The CFU-E gives rise to smaller colonies
➔ The estimated time spent at each stage
suggests that it takes about 1 week for the
BFU-E to mature to the CFU-E and another
week for the CFU-E to become a
pronormoblast
Pronormoblast - the first morphologically
identifiable RBC precursor
● Erythroid Precursors
○ The earliest morphologically recognizable
erythrocyte precursor, the pronormoblast
○ Pronormoblast proliferation is similar to the
proliferation of other cell lines
○ It is a process of encompassing replication,
example division that increases cell numbers
at development from immature to mature cell
stages
○ The earliest morphologically recognizable
erythrocyte precursor, the pronormoblast,
derived via BFU-E and and CFU-E from
pluripotent hematopoietic stem cells
○ The pronormoblast is able to divide with
each daughter maturing to next stage of the
development, the basophilic normoblast
○ Each of these cells divide again while each
of its daughter cell mature to the next stage,
polychromatic normoblast, and each of these
cells can also divide and mature
● Criteria used in identification of Erythroid
Precursors
○ Overall diameter of the cell decreases
○ Diameter of the nucleus decrease more
rapidly than does the diameter of the cell.
As a result the nucleus-cytoplasm ratio also
decreases
○ Nuclear chromatin pattern becomes coarser,
clumped, and condensed
■ The nuclear chromatin of erythroid
precursors is coarser than myeloid
precursors, it becomes even
coarser and clumped as the cells
matures developing a raspberry like
appearance in which the dark
staining of the chromatin as distinct
from almost white appearance of
parachromatin
■ This chromatin distinction is more
dramatic than other cell lines
■ Ultimately, the nucleus becomes
quite condensed with no
parachromatin evident at all
■ Nucleus is said to be pyknotic
○ Nucleoli disappear
■ The nuclei represent areas where
the ribosomes are formed and seen
early in the cell development
■ As cells become actively
synthesizing proteins. As erythroid
precursors mature the nucleoli
disappear which precedes the
ultimately cessation of protein
synthesis
○ Cytoplasm changes from blue to gray-blue to
salmon pink
■ The blueness or basophilia is due
to the acidic components that
attract the basic stain such as
methylene blue
Figure 3.1 General trends affecting the morphology of
erythroid precursors during the developmental process
● (A) Cell diameter decreases and cytoplasm
changes from blue to salmon pink
● (B) Nuclear diameter decreases and color
changes from purplish-red to a very dark
purple-blue
● (C) Nuclear chromatin becomes coarser, clumped,
and condensed
● (D) Composite of changes during the
developmental process / Combined changes of
A,B,C
IV. RED BLOOD CELL
● The major function or the erythrocyte has one true
function: It is to carry oxygen from the lung to the
tissues. Where the oxygen is released
● This is accomplished by the attachment of oxygen to
hemoglobin, the major cytoplasmic component of
mature RBCs.
● The role of RBCs in returning carbon dioxide to the
lungs and buffering the pH of the blood is important
 because it is quite secondary to its oxygen carrying ● NUCLEUS: The nucleus is round to oval, containing
function one or two nucleoli. The purple red chromatin is open
○ Acid base buffer and contains few, if any, fine clumps
○ Biconcave in shape ● CYTOPLASM: Basophilic
○ Distensible ● NC Ratio: High (8:1)
○ ● Forms two basophilic normoblast after mitosis
● The pronormoblast is present only in the bone marrow
in healthy states

Table 1 Three erythroid precursor nomenclature systems

Normoblastic Rubriblastic Erythroblastic

Pronormoblast Rubriblast Proerythroblast

Basophilic Prorubricyte Basophilic

normoblast erythroblast

Polychromatic Rubicyte Polychromatic

(polychromatophili (polychromatophili
c) normoblast c) erythroblast

Orthochromic Metarubricyte Orthochromic

normoblast erythroblast BASOPHILIC NORMOBLAST
● NUCLEUS: The chromatin begins to condense,
Polychromatic Polychromatic Polychromatic revealing clumps along the periphery of the nuclear
(polychromatophili (polychromatophili (polychromatophili membrane and a few in the interior
c) erythrocyte c) erythrocyte c) erythrocyte ● CYTOPLASM: deeply basophilic. The cytoplasm is
dark blue because of the concentration of ribosomes
Erythrocyte Erythrocyte Erythrocyte and RNA
● NC Ratio: Moderate (6:1)
! Polychromatic erythrocytes are called reticulocytes when
● The basophilic normoblast undergoes mitosis, giving
observed with vital stains.
rise to two daughter cells
● Pronormoblast is the same as rubriblast, rubriblast is
● The basophilic normoblast is present only in the bone
the same as proerythroblast and so on
borrow in healthy states
● Although the end product of normoblastic, rubriblastic,
● Detectable hemoglobin synthesis occurs
and erythroblastic is all the same, they are all called
reticulocytes in the end
● But along the way they differ in the
normoblastic:basophilic normoblast,
rubriblastic:prorubricyte, erythroblastic:basophilic
erythroblast

Table 2 Maturation Sequence of Erythropoiesis (RBC POLYCHROMATIC NORMOBLAST

Production and Maturation) ● NUCLEUS: The condensation of chromatin reduces
the diameter of the nucleus considerably
PRONORMOBLAST ● CYTOPLASM: deeply basophilic because this is the
● Aka Proerythroblast first stage in which the pink color associated with
● First microscopically recognizable precursor cell stained hemoglobin can be seen
in erythropoiesis ○ Stained color reflects the accumulation of
○ Largest erythropoiesis precursor and highest hemoglobin pigmentation and overtime and
content of RNA concurrently increasing the amounts of RNA,
 the color produces a mixture of pink and blue
resulting in a murky gray blue cytoplasm
● NC ratio: Moderate
● Last stage which contains a nucleus
● Last stage capable of mitosis
○ Producing daughter cells that mature and
development into Orthochromatic normoblast
● During the first several days after exiting the bone
marrow, the polychromatic erythrocyte is retained in
the spleen for pitting of inclusions, if it has any, and
the membrane polishing by splenic macrophages
which results a biconcave discoid mature RBCs

ORTHOCHROMATIC NORMOBLAST
● Aka Metarubricyte
● NUCLEUS: The nucleus is completely condensed ERYTHROCYTES
(i.e., pyknotic) or nearly so ● Life span: 120 days
● CYTOPLASM: pink gray (more pinkish) ○ Mature RBCs remain active in the circulation
○ The increase in the salmon pink color of the approximately 120 days
cytoplasm reflects nearly complete ○ Aging leads to the removal by the spleen as
hemoglobin production described subsequently
● NC Ratio: low ● No nucleus, mitochondria, or endoplasmic reticulum
● No longer capable of division ● The mature circulating erythrocyte is a biconcave
disc measuring 7 to 8 “m in diameter, with a thickness
of about 1.5 to 2.5 ”m
● On a Wright-stained blood film. It appears as a
salmon-pink stained cell with a central pale area that
corresponds to the concavity. The central pallor is
about one-third the diameter of the cell
● Contains cytoplasmic enzymes capable of
metabolizing glucose
○ Able to transform small amounts of ATP

POLYCHROMATIC ERYTHROCYTE
● Aka Reticulocyte
● First anucleated precursor
● RNA synthesis stops while heme synthesis continue
● Loses its RNA and mitochondria
● NUCLEUS: none
● CYTOPLASM: pink gray
○ By the end of the polychromatic erythrocyte
stage, the cell is the same color as a mature
RBC, salmon pink
○ It remains larger than a mature cell, however
● Resides in the bone marrow for about 1 to 2 days
and then moves into the peripheral blood for about 1
day before reaching maturity
 V. ERYTHROKINETICS
● Is the term describing the dynamics of RBC
production and destruction
● The rule of the RBC is to carry out oxygen, to regulate
this production of RBCs for that purpose, the body
requires a mechanism for sensing whether there is
adequate oxygen being carried to the tissues. If tissue
oxygen is adequate, RBC production and the
functional efficiency of existing cells must be
enhanced
● A second feature of the oxygen-sensing system must
be a mechanism for influencing production of RBCs
● The primary oxygen-sensing system of the body is
located in peritubular fibroblasts of the kidney
● Hypoxia is detected by the peritubular fibroblasts,
which then produce erythropoietin (EPO), the major
stimulator cytokine for RBC
○ Hypoxia - too little tissue oxygen
● Under normal circumstances, the amount of the EPO
produced secretes very little, maintaining a level of
RBC production that is sufficient to replace
approximately 1% of RBCs that normally die each day
● It is well documented that testosterone directly
stimulates erythropoiesis, which partially explains the
higher hemoglobin concentration in men than in
women
ERYTHROPOIETIN
● Also known as EPO, is a thermostable, nondialyzable,
glycoprotein hormone with a molecular weight of 34
kD
● It consists of a carbohydrate unit and a terminal sialic
acid
● Is a true hormone, being produced at one location
(kidney) and acting at a distant location (bone
marrow)
● It is a growth factor (or cytokine) that initiates an
intracellular message to the developing erythroid
cells; this process is called signal transduction
● EPO has three major effects:
○ (1) allowing early phase of reticulocytes
from the bone marrow.
- The nucleated RBCs (erythroblasts/
normoblasts) can be released early
in cases of extreme anemia when
the demand for RBCs in the
peripheral circulation is great.
- Releasing cells from the bone
marrow early is a quick fix or a
band aid solution - it is limited in the
effectiveness because the available
precursors in the marrow are
depleted within several days, and
still may not be enough to meet the
needs of the peripheral blood for
more cells.
- If there's not a lot of hemoglobin in
the early nucleated RBCs, the
effectivity of those cells will be quite
low in delivering oxygen
○ (2) preventing apoptotic cell death
- A more important mechanism by
which the EPO increases the
number of circulating RBCs is by
increasing the number of cells that
would be able to mature. It does
this by decreasing the apoptosis or
the program death of RBC
progenitors .
- One effect of EPO is indirect
avoidance of apoptosis by removing
the apoptosis induction signal
○ (3) reducing the time needed for cells to
mature in the bone marrow
- Increases the rate at which the
surviving precursors can enter the
circulation (gipadali niya ang
maturation)
- It is accomplished by two means:
➔ An increased rate of
cellular processes; or
➔ A decrease in the cell
cycle times
- The other process that is
accelerated is the association of the
division. Cell division takes time
and would delay the entry of cells in
the circulation
- Cells enter cell arrest sooner so it
can mature, as a result the cells will
spend time maturing the bone
marrow. So in the circulation, such
as are larger because of the loss of
mitotic divisions (they do not have
time before entering the circulation
to dismantle the protein production
machinery that gives the bluish
tinge to the cytoplasm
- So with the decreased cell time, the
time it takes from the
pronormoblastic reticulocytes can
be shortened about 2 days in total
because if the reticulocyte leaves
the marrow early, another day can
be saved
- So the essence is that the EPO
puts more RBCs in the circulation at
a faster rate, then occurs without its
stimulation
VI. LEUKOPOIESIS
● The process of generating white blood cells
(leukocytes) from the pluripotent Hematopoietic
Stem Cells of the Bone Marrow.
● There are two significant pathways to generate
various types of leukocytes:
○ Myelopoiesis - in which the leukocytes in
the blood are derived from Myeloid Stem
Cells
○ Lymphopoiesis - in which leukocytes of the
lymphatic system (lymphocytes) are
generated from lymphoid stem cells
● Factors that promote differentiation of the
CFU-GEMM into neutrophils, monocytes, eosinophils,
and basophils include GM-CSF, G-CSF, macrophage
colony-stimulating factor (M-CSF), IL-3, IL-5, IL-11,
and KIT Ligand.
○ The GM-CSF stimulates the proliferation and
differentiation of the neutrophil & the
macrophage colonies from the colony
 forming unit granulocyte, monocyte or the
GEMM
○ The G-CSF and the monocyte CSF stimulate
neutrophil differentiation & monocyte
differentiation from the colony forming unit
granulocyte or CFU-M
○ Interleukin-3 is a multi-lineage stimulating
factor, so it can be found anywhere. It
stimulates the growth of granulocytes,
monocytes, and megakaryocytes.
○ The eosinophils require GM-CSF,
interleukin-5 & interleukin-3 for differentiation
○ The basophil differentiation depends on
the presence of interleukin-3 and KIT-Ligand
○ Growth factors that promote lymphoid
differentiation include interleukin-2,
interleukin-7, interleukin-12, & interleukin-15
(To some extent it includes interleukins 4, 10,
13,14, & 16)
VII. NEUTROPHIL DEVELOPMENT
● Occurs in the bone marrow
● Neutrophils share a common progenitor with
monocytes and are distinct from eosinophils and
basophils, known as the granulocyte monocyte
progenitor (GMP).
● The major cytokine responsible for the stimulation of
neutrophil production is granulocyte colony-
stimulating factor, or G-CSF.
● There are three pools of developing neutrophils in the
bone marrow:
○ The stem cell pool
- Consists of HSCs (Hematopoietic
Stem Cells) that are capable of
self-renewal and differentiation
○ The proliferation (mitotic) pool
- Consists of cells that are dividing
and includes common myeloid
progenitors (CMPs), CFUGEMMs,
and Granulocyte-monocyte
progenitors
○ The maturation (marrow) pool
- Consists of cells undergoing
nuclear maturation that form the
marrow reserve and are available
for release: metamyelocytes, band
neutrophils, and segmented
neutrophils
A. MYELOBLAST
● Make up 05 to 3% of the nucleated cells in the bone
marrow and measure 14 to 20” m in diameter
● Are often subdivided into type I, type II, and type III
myeloblasts
● First recognizable cell that begin the process of
granulopoiesis
● Earliest microscopically recognizable neutrophil
precursor cell in the bone marrow
● Large euchromatic spherical nucleus with three to five
nucleoli
● Large nuclear to cytoplasmic volume
● The small amount of agranular cytoplasm stains
intensely basophilic
B. PROMYELOCYTE
● Comprises 1% to 5% of the nucleated cells in the
bone marrow.
● Are relatively larger than the myeloblast cells and
measure 16 to 25” m in diameter.
● The nucleus is round to oval and is often eccentric
● Only cells to produce azurophilic granules
● Azurophilic (primary) granules in the cytoplasm
C. MYELOCYTES
● First that exhibit specific granules
● Last stage capable of Mitosis
● Recognition of the neutrophil, eosinophil, and
basophil lines is possible
○ Neutrophil
- Patches of grainy pale pink
cytoplasm representing secondary
granules begin to be evident in the
area of the Golgi apparatus. This
has been referred to as the dawn
of neutrophilia
○ Eosinophil
- Characterized by the presence of
large, pale, reddish orange
secondary granules, along with
azure in blue cytoplasm. The
nucleus is similar to that described
for neutrophil myelocytes
D. METAMYELOCYTE
● Constitute 3% to 20% of nucleated marrow cells
● From this stage forward, the cells are no longer
capable of division and the major prophologic change
is in the shape of the nucleus
● The nucleus is indented (kidney bean shaped or
peanut shaped), and the chromatin is increasingly
clumped. Nucleoli are absent
● Synthesis of tertiary granules (also known as
gelatinase granules) may begin during this stage
● The size of metamyelocyte is slightly smaller than that
of the myelocyte (14 to 16” m)
● The cytoplasm contains very little residual ribonucleic
acid (RNA) and therefore little or no basophilia
E. BAND (STAB) CELL
● Bands make up 9% to 32% of nucleated marrow cells
and 0% to 5% of the nucleated peripheral blood cells
● All evidence of RNA (cytoplasmic basophilia) is
absent, and tertiary granules continue to be formed
during this stage
● Secretory granule (also known as secretory
vesicles) may begin to be formed during this stage
● The nucleus is highly clumped, and the nuclear
indentation that began in the metamyelocyte stage
now exceeds one half the diameter of the nucleus, but
actual segmentation has not yet occured
F. MATURE GRANULOCYTE
● Segmented neutrophils
○ Make up 7% to 30% of nucleated cells in the
bone marrow. Secretory granules continue to
be formed during this stage. The only
morphologic difference between segmented
neutrophils and bands is the presence of
between two and five nuclear lobes
connected by thread-like filaments
● Mature eosinophils
○ Usually display a bilobed nucleus. Their
cytoplasm contains characteristic refractile,
orange-red secondary granules
Table 3 Different Functions of Neutrophils, Eosinophils,
and Basophils
G. MONOCYTES
● Appears to be larger than neutrophils (diameter of 15
to 20” m) because they tend to stick to and spread
out on glass or plastic. (it is very hard to find them)
● Monocytes are slightly immature cells whose ultimate
goal is to enter the tissues and mature into
macrophages, osteoclasts, or dendritic cells
● The nucleus may be round, oval, or kidney shaped
but more often is deeply indented (horseshoe
shaped) or folded on itself
● The chromatin pattern is looser than in the other
leukocytes and has sometimes been described as
lace-like or stringy
● Their cytoplasm is blue gray with fine azure granules
often referred to as azure dust or a ground-glass
appearance.
● Monocytes remain in the circulation approximately 3
days. Monocytes with different patterns of chemokine
receptors have different target tissues and different
functions
● Mononuclear phagocyte system (reticuloendothelial
system)
● Defense against microorganism including
mycobacteria, fungi, bacteria, protozoa, and viruses
● Called histocytes or macrophage when it migrates
to the tissue
 Table 4 Monocyte Destinations
H. LYMPHOCYTES
● Are divided into three major groups: T cells, B cells,
and natural killer (NK) cells
○ T and B cells are major players in adaptive
immunity
○ NK cells make up a small percentage of
lymphocytes and are part of innate immunity
● Lymphocytes can be subdivided into two major
categories: Those that participate in humoral
immunity by producing antibodies and those that
participate in cellular immunity by attacking foreign
organisms or cells directly
● Antibody-producing lymphocytes are called B
lymphocytes or simply B cells because they
develop in the bone marrow
● Cellular immunity is accomplished by two types of
lymphocytes: T cells, so named because they develop
in the thymus, and NK cells, which develop in both
the bone marrow and the thymus
● NK lymphocytes function as part of innate immunity
and are capable of killing certain tumor cells and
virus-infected cells without prior sensitization
○ In addition, NK cells modulate the functions
of other cells, including macrophages and T
cells.
● Are different from the other leukocytes in several
ways, including the ff:
○ Lymphocytes are not end cells. They are
resting cells, and when stimulated, they
undergo mitosis to produce both memory
and effector cells
○ Unlike other leukocytes, lymphocytes
reticulate from the blood to the tissues and
back to the blood
○ B and T lymphocytes are capable of
rearranging antigen receptor gene
segments to produce a wide variety of
antibodies and surface receptors
○ Although early lymphocyte progenitors such
as the common lymphoid progenitor
originate in the bone marrow, T and NK
lymphocytes develop and mature outside
the bone marrow
Table 4 Summarization of Lymphocytes
VIII. PLATELETS
● Platelets come from pluripotent hematopoietic stem
cells, going to the common myeloid progenitor, going
to the megakaryocyte-erythrocyte progenitor. That’s
where they differentiate into the megakaryoblasts,
megakaryocyte, and platelets
MEGAKARYOPOIESIS
● Platelets arise from unique bone marrow cells called
megakaryocytes.
● Megakaryocytes are the largest cells in the bone
marrow and possess multiple chromosome copies
(polyploid)
● Is the process by which megakaryocytes and
ultimately platelets develop
● Earlier influences include GM-CSF, IL-3, IL-6, IL-11,
KIT Ligand, and TPO. The stimulating hormonal
factor TPO (also known as MPL Ligand), along with
IL-11, controls the production and release of platelets.
The liver is the main site of production of TPO
● Megakaryocyte progenitors arise from the common
myeloid progenitor under the influence of the
transcription gene product, GATA-1, regulated by
cofactor FOG1
● Megakaryocyte differentiation is suppressed by
another transcription gene product, MYB, so GATA-1
and MYB act in opposition to balance
megakaryocytopoiesis with erythropoiesis
● Three megakaryocyte lineage-committed progenitor
stages, defined by their in vitro culture colony
characteristics, arise from the common myeloid
progenitor. In order of differentiation, these are:
○ The least mature burst-forming unit
(BFU-Meg)
○ The intermediate colony forming unit
(CFU-Meg)
○ The more mature progenitor, the
light-density CFU (LD-CFU-Meg)
○ All three progenitor stages resemble
lymphocytes and cannot be distinguished
by wrightstained light microscopy
 Figure 3.1 Bone Marrow Aspirate

(A), The megakaryoblast (MK-I) (arrow) resembles the

myeloblast and pronormoblast (rubriblast); identification
by morphology alone is inadvisable. This megakaryoblast
has cytoplasmic “blebs” that resemble platelets
(B), Promegakaryocyte (MK-II). Cytoplasm is abundant,
and the nucleus has minimal lobularity.
(C), Megakaryocyte (MK-III). The nucleus is lobulated with
basophilic chromatin. The cytoplasm is azurophilic and
granular, with evidence of the demarcation system (DMS)
(D), Terminal megakaryocyte shedding platelets from the
proplatelet process.

THROMBOCYTOPOIESIS
● AKA Platelet Shedding
● Illustrates the process of platelet shedding, termed
thrombocytopoiesis, a single megakaryocyte may
shed 2000 to 4000 platelets.
● The total platelet population turns over in 8 to 9 days
(the so-called platelet lifespan)