Hematopoietic System
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Functional Anatomy & Hematopoiesis
HEMATOPOIETIC SYSTEM
The term hematopoietic system refers to the organs collectively, which form and contain
cells of the blood and related supporting cells. This include blood vessels and cells of the
blood, bone marrow, lymph node, thymus, spleen, tonsils and adenoids, extranodal
lymphoid tissues such as appendix, mucosa-associated lymphoid tissue in various organs
such as lung and gastrointestinal tract, and the mononuclear phagocyte system throughout
the body. Shown below is the hematopoietic system excluding the blood vessels.
[This picture is adapted from Immunology by Roitt et al, 5th edition. Mosby Press]
HEMATOPOIESIS:
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Hematopoietic System
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Functional Anatomy & Hematopoiesis
Hematopoiesis is a complex, highly integrated, and coordinated process that begins early
in life at about 5 weeks of embryonic age in the yolk sac and with further growth, it
occurs in several other organs at various ages of life.
[This picture is adapted from HEMATOLOGY: Basic Principles & Practice by Hoffman et al. 3 rd ed. Churchill-Livingstone]
In postnatal life, hematopoiesis switches mostly to bone marrow and in adults, under
physiological conditions, it occurs in bone marrow only. The bone marrow
microenvironment plays an essential role in the process of hematopoiesis. Pluripotent
hematopoietic stem cell (HSC), stromal cells & the extracellular matrix (ECM) including
proteoglycans maintain a dynamic relationship with each other so that under the influence
of growth promoting soluble factors, stem cells differentiate into mature cells supported
by the a microenvironment that is rich in stromal cells and extracellular scaffolding.
[This picture is adapted from HEMATOLOGY: Basic Principles & Practice by Hoffman et al. 3 rd ed. Churchill-Livingstone]
What triggers hematopoiesis? Simply a need by the body as assessed by an imbalance in
the various soluble factors secreted by hematopoietic cells and other organs. For example,
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material for teaching purposes only. No commercial incentives are sought or intended.
Hematopoietic System
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Functional Anatomy & Hematopoiesis
lack of red blood cells leads to tissue hypoxia, which in turn causes the release of a
soluble factor by the kidneys called erythropoietin (EPO). This factor, in conjunction
with others, acts on HSC and cause them to differentiate into RBCs. Likewise, a lack of
platelets causes release of thrombopoietin, which in turn leads to differentiation of HSC
to megakaryocytes. A number of soluble growth factors have been identified; some of
which cause early differentiation of HSC whereas other only come into play at the final
stages of maturation and differentiation. An overview of hematopoiesis is shown below.
[These pictures are adapted from Robbins Pathologic Basis of Diseases, 6th edition, W.B Saunders Co.]
ERYTHROPOIESIS:
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material for teaching purposes only. No commercial incentives are sought or intended.
Hematopoietic System
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Functional Anatomy & Hematopoiesis
The various maturing stages of erythroid precursors and their growth factors are shown
below:
[This picture is adapted from Williams Hematology by Beutler et al. 6th edition. McGraw Hill Press]
[This picture is adapted from HEMATOLOGY: Basic Principles & Practice by Hoffman et al. 3 rd ed. Churchill-Livingstone]
MYELOMONOPOIESIS:
The various maturing stages of myelomonocytic precursors and their growth factors are
shown below:
[This picture is adapted from BLOOD: Principles & Practice of Hematology by Handin et al. Lippincott Press]
[This picture is adapted from BLOOD: Principles & Practice of Hematology by Handin et al. Lippincott Press]
The contents & pictures in this handout are derived from various sources including books, journal articles and patient
material for teaching purposes only. No commercial incentives are sought or intended.
Hematopoietic System
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Functional Anatomy & Hematopoiesis
[This picture is adapted from HEMATOLOGY: Basic Principles & Practice by Hoffman et al. 3rd ed. Churchill-Livingstone]
MEGAKARYOPOIESIS:
The differentiation to megakaryocytes and their growth factors are shown below:
[This picture is adapted from HEMATOLOGY: Basic Principles & Practice by Hoffman et al. 3rd ed. Churchill-Livingstone]
LYMPHOPOIESIS:
B-CELL DEVELOPMENT:
In the bone marrow, hematopoietic stem cells yield progeny that differentiate into B
lymphoblasts. After IgH and IgL have rearranged, these B lymphoblasts undergo a
sequence of morphologic and phenotypic changes and exit the marrow. In the peripheral
blood these naïve B cells home to the mantle zones in lymph nodes, where they wait for
antigen to be delivered in lymph drainage. At the point of antigen exposure, the naïve B
cells undergo a sequence of morphologic and phenotypic changes and migrate into
germinal centers. In the germinal centers these large “centroblasts” undergo somatic
hypermutation of IgH and IgL in the germinal center, and then reduce in size to become
small “centrocytes”. The selected centrocytes are able to exit the germinal center, where
they undergo additional morphologic and phenotypic changes to become either memory
B-cells (in the marginal zone) capable of initiating a secondary immune response or they
become the effector cells of the humoral immune system – plasma cells.
The contents & pictures in this handout are derived from various sources including books, journal articles and patient
material for teaching purposes only. No commercial incentives are sought or intended.
Hematopoietic System
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Functional Anatomy & Hematopoiesis
[These pictures are adapted from Robbins Pathologic Basis of Diseases, 6th edition, W.B Saunders Co.]
T-CELL DEVELOPMENT:
In the bone marrow, hematopoietic stem cells yield progeny that differentiate into T
lymphoblasts (TdT+). After the T-cell receptors  &  have rearranged, these T
lymphoblasts undergo a sequence of morphologic and phenotypic changes and exit the
marrow. In the peripheral blood these naïve T-cells home first to the subcapsular region
(early thymocytes) and then to the cortex of the thymus (common thymocytes) where
they interact with cortical epithelial cells (which bear MHC and self-antigens). Only
those naïve T-cells that can bind to the MHC-antigen complex are positively selected;
naïve T-cells that cannot bind properly to the MHC moiety are de-selected (apoptosis) at
the cortical thymic stage. Positively selected naïve T-cells undergo a sequence of
morphologic and phenotypic changes and migrate to the thymic medulla, where they
again interact with dendritic cells bearing MHC & self-antigen. Those medullary T-cells
that have a high affinity for the MHC-self antigen complex are de-selected because they
are autoreactive, and those that have weak affinity for self-antigen receive positively
selective stimuli and migrate into the peripheral blood. From the peripheral blood these
‘educated’ T cells can exit the circulation and enter the lung, GI tract, and lymph nodes
where they function as effector cells capable of initiating cell mediated cytotoxicity.
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material for teaching purposes only. No commercial incentives are sought or intended.
Hematopoietic System
Functional Anatomy & Hematopoiesis
The overall scheme of lymphopoiesis is shown below.
[This picture is adapted from BLOOD: Principles & Practice of Hematology by Handin et al. Lippincott Press]
FUNCTIONAL ANATOMY:
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material for teaching purposes only. No commercial incentives are sought or intended.
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Hematopoietic System
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Functional Anatomy & Hematopoiesis
The main function of the hematopoietic system is in immunity and inflammation by
white blood cells (WBC), hemostasis by platelets, and oxygen delivery to the body by red
blood cells (RBCs). Although, they appear to be separate functions, some are interrelated
such as thrombus formation requires cooperation of platelets, plasma proteins,
endothelium, red blood cells, and white blood cells. We shall discuss these organs in the
context of their function to facilitate an understanding of the interconnectedness of these
seemingly separate organs.
BONE MARROW:
In adults, under physiological conditions, bone marrow is the site of origin of all
hematopoietic cells from pluripotent, undifferentiated stem cells. Maturation of B-cells is
thought to occur in the bone marrow also, whereas maturation of T-cells takes place in
thymus. Bone marrow is a large organ within bone medulla and composed of stem cells,
immature and maturing hematopoietic cells, admixed adipocytes in varying amounts at
different ages, macrophages, supporting fibroblasts and other stromal cells, blood vessels
and venous sinuses. Traversing within the marrow are bony trabeculae lined by
osteoblasts and osteoclasts. Generally, the hematopoietic cells that can be
morphologically identified in the marrow include the myeloid series cells, erythroid
series cells, megakaryoctes, macrophages, mast cells, lymphocytes and, stromal cells.
A Leder stain shows red-orange myeloid series cells and dark unstained erythroid cells. Megakaryocytes
are larger multilobated cells. Stromal cells are lymphocytes also appear as unstained cells.
A range of maturing myeloid and erythroid cells can be seen in a marrow aspirate smear.
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material for teaching purposes only. No commercial incentives are sought or intended.
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Functional Anatomy & Hematopoiesis
All stages of myeloid maturation is present
A macrophage with iron is seen in the center
LYMPH NODE (LN):
In essence, a lymph node is a port where lymphocytes and cells derived from the
monocyte lineage reside and are in transit to venous blood. As such, a lymph node forms
part of a network, which filters antigens from interstitial tissue fluid & lymph during its
passage from the periphery to the thoracic duct and other major collecting duct.
[This picture is adapted from Immunology by Roitt et al, 5th edition. Mosby Press]
The lymph fluid brings in the lymphocytes and macrophages to the lymph node through
afferent lymphatic channels and leave through the efferent ducts. The LN consists of a Bcell area (cortex) and a T-cell zone (paracortex) and a central medulla, formed by cellular
cords and sinuses containing a mixture of B-cells, T-cells, plasma cells, and
macrophages. The cortex contain lymphoid follicles, primary and secondary; primary
follicles do not contain germinal centers whereas secondary follicles form as a result of
antigen stimulation of primary follicles and contain germinal center cells.
The contents & pictures in this handout are derived from various sources including books, journal articles and patient
material for teaching purposes only. No commercial incentives are sought or intended.
Hematopoietic System
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Functional Anatomy & Hematopoiesis
[This picture is adapted from Immunology by Roitt et al, 5th edition. Mosby Press]
The primary follicles consists of naïve B-cells that express the pan B-cell marker CD19
and, surface immunoglobulins of IgM and IgD subtype. These B-cells do not express
CD10 and do not show somatic hypermutations that occur only after antigen stimulation.
These cells, however, express CD27 and a subset also shows expression of CD5. Upon
antigen antigen stimulation through cell surface receptors (IgM or IgD & CD79), the
primary follicle B-cells transform morphologically and express a new of cell surface
markers and exhibit somatic hypermutation. In the secondary follicles, several distinct
zone could be demonstrate: a mantle zone, which is basically the non-transformed
primary follicle cells, a geminal center with dark zone, light zone and apical zone.
Adapted from Mackay & Rosen. NEJM, 2000;343:108-117.
The paracortex contain may antigen-presenting cells (APCs) that are called interdigitating
cells (IDC), which are monocyte derived cells and which express high levels of MHC
class II antigens and present antigens to T-cells. Similar to IDC, germinal centers contain
The contents & pictures in this handout are derived from various sources including books, journal articles and patient
material for teaching purposes only. No commercial incentives are sought or intended.
Hematopoietic System
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Functional Anatomy & Hematopoiesis
follicular dendritic cells (FDC) and macrophages. Germinal centers also contain CD4+ Tcells, which interact with FDC and help in B-cell maturation and differentiation. The
immunohistochemical localization of various cellular fractions of a secondary lymphoid
follicle is shown below.
CD79a in a follicle mantle & germinal center cells
bcl-2 staining the mantle zone B-cells but not GCC
CD21 in follicular dendritic cells
bcl-6 staining only germinal center cells (GCC)
THYMUS:
Thymus is the site for T-cell development and maturation of precursor T-cells derived
from bone marrow. The thymus is a lobulated organ consisting of a cortex and a medulla.
Unlike lymph node, however, the cortex does not normally contain lymphoid follicles.
Instead, it contains tightly packed precursor T-cells originated from bone marrow and
traversed through blood into the subcapsular region and then into the cortex. The
subcapsular thymocytes (early thymocytes) are, thus, the earliest thymic precursor T-cells
characterized by the expression of surface CD2, CD7 and TdT but no cyCD3, CD4, or
CD8. With further maturation into the cortex, the thymocytes express CD1, CD5 that
initially are negative for both CD4 and CD8 but later expresses both CD4 and CD8
together (Common thymocytes). With expression of CD3, these cells move down into the
medulla and express either CD4 (CD3+CD4+) or CD8 (CD3+CD8+) but not both. From
thence, the T-cells move on to circulate or reside in various tissues and organs.
The contents & pictures in this handout are derived from various sources including books, journal articles and patient
material for teaching purposes only. No commercial incentives are sought or intended.
Hematopoietic System
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Functional Anatomy & Hematopoiesis
[These pictures are adapted from Robbins Pathologic Basis of Diseases, 6th edition, W.B Saunders Co.]
SPLEEN:
The spleen is the largest lymphoid organ in the body. Based on the gross appearance, the
spleen is said to be composed of white pulp (WP) and red pulp (RP). The WP consists of
lymphoid tissue, the bulk of which is arranged around a central arteriole to form
periarteriolar lymphoid sheath (PALS) composed of T & B-cells; the T-cells are found
around the central arteriole; the B-cells may be organized into either primary
“unstimulated” follicles, or stimulated secondary follicles with germinal centers. The
follicle’s architecture is the same as in the lymph node except that the marginal zone is
much better developed in spleen and rarely prominent in lymph nodes. The RP contains
venous sinuses and cellular cords containing resident macrophages, RBCs, platelets,
lymphocytes, and numerous plasma cells.
[This picture is adapted from Immunology by Roitt et al, 5th edition. Mosby Press]
The contents & pictures in this handout are derived from various sources including books, journal articles and patient
material for teaching purposes only. No commercial incentives are sought or intended.