Formation of blood cells

1. Haemopoeisis
Dr Sufyan Akram

2. Bone Marrow
• In adults, bone marrow is the major site of
production of various blood cells
• In the fetus, blood cells are also formed in the
Liver and Spleen
• Active cellular marrow is called Red Marrow;
whereas inactive marrow that has been infiltrated
with fat is called Yellow Marrow
• Bone marrow indeed is one of the largest and most
active organs in the body !!

3. 66x
200x

5. From One to Many…

6. HSC
self-
renewal
CFU-
s
Erythrocytes
Megakaryocyte/
Platelets Granulocytes
Monocyte/
Macrophage
CLP
Lymphocytes

7. Hematopoietic Stem Cells
(HSCs)
• The blood cells begin their lives in the bone
marrow from a single type of cell called the
pluripotent hematopoietic stem cell, from which
all the cells of the circulating blood are eventually
derived
• As these cells reproduce, a small pool of these
cells is maintained throughout life to maintain a
continuous supply

8. Hematopoietic Stem Cells
(HSCs)
• The best current source of these stem cells is
“Umbilical Cord Blood”
• Have you heard of Cord blood banks ??

9. Haematopoietic
Stem Cells
Mature Blood
Cells
Growth
Inducers
Differentiation
Inducers

10. Growth Inducers
• Growth and reproduction of the different stem
cells are controlled by multiple proteins called
growth inducers or factors
• One of these, interleukin-3, promotes growth and
reproduction of virtually all the different types of
committed stem cells, whereas the others induce
growth of only specific types of cells

11. Differentiation Inducers
• The growth inducers promote growth but not
differentiation of the cells. This is the function of
another set of proteins called differentiation
inducers
• Each of these causes one type of committed stem
cell to differentiate one or more steps toward a
final adult blood cell

12. Red Blood Cells

13. Proerythroblast Basophilic
erythroblast
Polychromatic
erythroblast
Acidophil
erythroblast
Reticulocyte Erythrocyte
Erythropoiesis

14. RBCs
• CFU-E stem cells differentiate into proerythroblast
• It divides multiple times, eventually forming many
mature red blood cells
• In the succeeding generations, the cells become
filled with hemoglobin to a concentration of about
34 %, the nucleus condenses to a small size, and its
final remnant is absorbed or extruded from the cell

16. Regulation of RBCs Production
• Tissue Oxygenation Is the Most Essential
Regulator of Red Blood Cell Production
• The principal stimulus for red blood cell production
in low oxygen states is a circulating hormone
called erythropoietin, a glycoprotein with a
molecular weight of about 34,000
• Erythropoietin is secreted by specialized cells in
the Kidney

18. Regulation of RBCs Production
• When a person moves to an atmosphere of low
oxygen, erythropoietin begins to be formed within
minutes to hours, and it reaches maximum
production within 24 hours
• But it takes about 5 days before increased number
of RBCs enter the blood
• Erythropoietin stimulates the production of
proerythroblasts from hematopoietic stem cells in the
bone marrow

19. Maturation of RBCs
• The erythropoietic cells of the bone marrow are
among the most rapidly growing and reproducing
cells in the entire body
• Therefore, their maturation and rate of production
are affected greatly by a person's nutritional status
• Especially important for final maturation of the red
blood cells are two vitamins, vitamin B12 and folic
acid

20. Maturation of RBCs
• Both vitamin B12 and folic acid are essential for the
synthesis of DNA because each, in a different way,
is required for the formation of thymidine
triphosphate, one of the essential building blocks
of DNA
• Lack of either vitamin B12 or folic acid causes
abnormal and diminished DNA and, consequently,
failure of nuclear maturation and cell division

21. Maturation of RBCs
• Furthermore, the erythroblastic cells of the bone
marrow, in addition to failing to proliferate rapidly,
produce mainly larger than normal red cells called
macrocytes and the cell itself has a flimsy
membrane and is often irregular, large, and oval
instead of the usual biconcave disc

22. Iron
Deficiency
Vit B12 or
Folate
Deficiency

23. White Blood Cells

24. WBCs
• Aside from those cells committed to form red
blood cells, two major lineages of white blood
cells are formed, the myelocytic and the
lymphocytic lineages
• The granulocytes, monocytes and megakaryocytes
are formed only in the bone marrow
• Lymphocytes are produced mainly in the lymphatic
tissues- especially the lymph glands, spleen and
thymus

25. Myeloid
stem cell
Myeloblast
Basophil progenitor
Eosinophil progenitor
Neutrophil progenitor
Basophil granulocyte
Eosinophil granulocyte
Neutrophil granulocyte
Myelopoiesis (1)

26. Myeloid
stem cell
Monoblast
Megakaryoblast Megakaryocyte
Monocyte
Platelets
Macrophage
Myelopoiesis (2)

27. Regulation of WBCs Production
• Granulocyte macrophage colony-stimulating factor
(GM-CSF) is a protein secreted by macrophages, T
cells, mast cells, NK cells, endothelial cells and
fibroblasts
• GM-CSF is a cytokine that functions as a white
blood cell growth factor. GM-CSF stimulates stem
cells to produce granulocytes (neutrophils,
eosinophils, and basophils) and monocytes

28. Myelopoiesis
• The white blood cells formed in the bone marrow
are stored within the marrow until they are
needed in the circulatory system. Then, when the
need arises, various factors cause them to be
released
• Megakaryocytes are also formed in the bone
marrow. These megakaryocytes fragment in the
bone marrow; the small fragments, known as
platelets (or thrombocytes), then pass into the
blood

29. Lymphopoiesis
Hematopoietic
stem cell
Pluripotent
stem cell
Lymphoid
stem cell
NK cell
T lymphocyte
B lymphocyte

30. Lymphopoiesis
• The lymphocytes are mostly stored in the various
lymphoid tissues where they undergo maturation,
except for a small number that are temporarily
being transported in the blood
• Their numbers increase in circulation only when
required

31. T and B Lymphocytes
• T and B lymphocytes are indistinguishable
histologically
• However T and B lymphocytes are very distinct cell
lineages and they ‘grow up’ or ‘mature’ in
different places in the body.
• They are also biochemically distinct and this is
reflected in the different markers and receptors
present on their cell surfaces

32. T Lymphocytes
• T cells are formed in bone marrow then migrate to
the cortex of the thymus to undergo maturation in
an antigen-free environment
• Only 2-4% of the T cells succeed. The remaining 96-
98% of T cells die by apoptosis and are
phagocytosed by macrophages in the thymus
• So many T cells die during the maturation process because
there is intensive screening to make sure each T cell has
the ability to recognize self (self tolerance)

33. T Lymphocytes
• Upon maturity, there are several forms of T
lymphocytes:
• T-helper (needed for activation of other cells such as B
cells and macrophages),
• T-cytotoxic (which kill virally infected cells),
• T-memory (T cells that remember antigens previously
encountered), and
• T-suppressor cells (which moderate the immune response
of other leukocytes)
• When T-Cells become activated they undergo a
further series of developments

34. B Lymphocytes
• B cells are formed and mature in bone marrow
(and spleen).
• These B cells then leave the bone marrow and
migrate to peripheral lymphoid tissues, such as a
lymph node. Once in a secondary lymphoid organ
the B cell can be introduced to an antigen that it is
able to recognize.
• Through this antigen recognition and other cell
interactions the B cell becomes activated and then
divides and differentiates to become a plasma cell.

35. B Lymphocytes
• The plasma cell, is a very active antibody-secreting
cell that helps protect the body by attacking and
binding to antigen
• Some B cells, upon activation, become memory
cells. They remain dormant, but upon the attack of
same antigen in future can quickly transform into
plasma cells and start making antibodies

36. Helper T Lymphocytes
B Lymphocytes Antibodies
Cell-mediated Immunity
Antibody-mediated Immunity
Cytotoxic T Lymphocytes
Cytokines
Direct killing
of Microbes
Bind to
invading
Antigens

37. References
Guyton and Hall Textbook of Medical Physiology, 12th
edition, 2011
Naish Medical Sciences, 1st edition, 2011