HEMATOPOISESHEMATOPOISES

THE FORMATION OF BLOOD CELLULAR THE FORMATION OF BLOOD CELLULAR COMPONENTS.COMPONENTS.

ALL THE BLOOD CELULAR COMPONENTS IS ALL THE BLOOD CELULAR COMPONENTS IS DERIVED BY HEMATOPOIETIC STEM CELLS DERIVED BY HEMATOPOIETIC STEM CELLS

HEMATOPOIETIC STEM CELLS HEMATOPOIETIC STEM CELLS (HSC)(HSC)

IS LOCATED AT BONE MARROW.IS LOCATED AT BONE MARROW.

HSC - HAS SPECIAL CHARACTERISTIC WHERE IT HSC - HAS SPECIAL CHARACTERISTIC WHERE IT CAN SELF-RENEWINGCAN SELF-RENEWING

ONCE HSC PROLIFERATE,THERE PRODUCE 2 ONCE HSC PROLIFERATE,THERE PRODUCE 2 DAUGHTER CELL.DAUGHTER CELL.

# 1 STEM CELL WILL REMAIN .# 1 STEM CELL WILL REMAIN .

# OTHER STEM CELL WILL PRODUCE EITHER # OTHER STEM CELL WILL PRODUCE EITHER

LYMPHOID STEM CELL(LSC) AND MYELOID LYMPHOID STEM CELL(LSC) AND MYELOID

STEM CELL(MSC).STEM CELL(MSC).

STEM CELLS THAT GIVES RISE TO ALL BLOOD CELLS STEM CELLS THAT GIVES RISE TO ALL BLOOD CELLS TYPES IS INCLUDING:-TYPES IS INCLUDING:-

1. LYMPHOID STEM CELL:1. LYMPHOID STEM CELL:

# T-CELL# T-CELL

# B-CELL# B-CELL

# NATURAL KILLER (NK-CELL)# NATURAL KILLER (NK-CELL)

- IS THE TYPE OF CYTOXIC LYMPHOCYTES.- IS THE TYPE OF CYTOXIC LYMPHOCYTES.

2. MYELOID STEM CELL:2. MYELOID STEM CELL:

# MONOCYTES# MONOCYTES

# NEUTROPHILS# NEUTROPHILS

# BASOPHILS# BASOPHILS

# EOSINOPHILS# EOSINOPHILS

# ERYTHROCYTES# ERYTHROCYTES

# MEGAKARYOCYTES ---- PLATELETS# MEGAKARYOCYTES ---- PLATELETS

LineagesLineages

Erythroid cellsErythroid cells LymphoidLymphoid cellscells MyeloidMyeloid cells cells

- Oxygen carrying RBC - Cornerstone of theOxygen carrying RBC - Cornerstone of the - Granulocytes, - Granulocytes, - Reticulocytes and Reticulocytes and adaptive immune system megakaryocytes and adaptive immune system megakaryocytes and

erythrocytes are erythrocytes are - T-cells and B-cells. - T-cells and B-cells. macrophages functional and macrophages functional and are are - Innate immunity, released into the - Innate immunity, released into the blood blood adaptive immunity, adaptive immunity,

and blood clotting. and blood clotting.

Before birth, hemopoiesis first occurs in the yolk sac of an embryo birth, hemopoiesis first occurs in the yolk sac of an embryo and later in the liver,spleen,thymus and lymph nodes of a fetus.and later in the liver,spleen,thymus and lymph nodes of a fetus.

Red bone marrow becomes the primary site of haemopoiesis in the Red bone marrow becomes the primary site of haemopoiesis in the last 3 months before birth and continues as the source of blood last 3 months before birth and continues as the source of blood cells after birth and throughout life.cells after birth and throughout life.

However,maturation , activation and some proliferation However,maturation , activation and some proliferation of lymphoid cells occurs in secondary lymphoid organs (spleen, of lymphoid cells occurs in secondary lymphoid organs (spleen, thymus,and lymph nodes).thymus,and lymph nodes).

In children, haematopoiesis occurs in the marrow of the long bones In children, haematopoiesis occurs in the marrow of the long bones such as the femur and tibia. such as the femur and tibia.

In adults, it occurs mainly in the pelvis, cranium, vertebrae, and In adults, it occurs mainly in the pelvis, cranium, vertebrae, and sternum.sternum.

LOCATION OF HAEMATOPOIESISLOCATION OF HAEMATOPOIESIS

extramedullaryextramedullary

In some cases, the liver, thymus, and In some cases, the liver, thymus, and spleen may resume their spleen may resume their haematopoietic function, if necessary. haematopoietic function, if necessary. This is called This is called extramedullary hematopoiesis. It may . It may cause these organs to increase in cause these organs to increase in size substantially. size substantially.

Blood cell Blood cell “Maturation”“Maturation”

As a stem cell matures it undergoes changes in As a stem cell matures it undergoes changes in gene expression that limit the cell types that it can become and moves it closer to a that limit the cell types that it can become and moves it closer to a specific cell type. specific cell type.

These changes can often be tracked by monitoring the presence of These changes can often be tracked by monitoring the presence of proteins on the surface of the cell.proteins on the surface of the cell.

Each successive change moves the cell closer to the final cell type Each successive change moves the cell closer to the final cell type and further limits its potential to become a different cell type .and further limits its potential to become a different cell type .

Blood cell Blood cell “Determination”“Determination”

Cell determination appears to be dictated by the location of Cell determination appears to be dictated by the location of differentiation. differentiation.

For the stem cells and other undifferentiated blood cells in For the stem cells and other undifferentiated blood cells in the bone marrow, the determination is generally explained the bone marrow, the determination is generally explained by the by the determinismdeterminism theory of hematopoiesis. theory of hematopoiesis.

Saying that colony stimulating factors and other factors of Saying that colony stimulating factors and other factors of the hematopoietic microenvironment determine the cells to the hematopoietic microenvironment determine the cells to follow a certain path of cell differentiation.follow a certain path of cell differentiation.

The ability of the bone marrow to regulate the quantity of The ability of the bone marrow to regulate the quantity of different cell types to be produced is more accurately different cell types to be produced is more accurately explained by a explained by a stochasticstochastic theory: theory:

Hemopoietic growth factors

are hormone-like substances (protein) that

stimulate bone marrow to produce blood cell and

promote the proliferation of blood cells

Erythropoietin (EPO) Is produces primarily by cells in the kidney that

lie between the kidney tubules ( peritubular interstitial

cells)

Control erythropoiesis

- red blood cell production

Increases the number of red blood cell precursors

Required for a myeloid progenitor cell to become

erythrocyte

Thrombopoietin ( TPO)

hormone produced by by the liver

stimulates the formation of platelets from megakaryocytes (megakaryocytopoiesis)

Transcription factors Transcription factors

•Growth factors initiate signal transduction Growth factors initiate signal transduction pathways, altering transcription factors and pathways, altering transcription factors and activate genes that determine the differentiation activate genes that determine the differentiation of blood cells. of blood cells.

•The early committed progenitors express low The early committed progenitors express low levels of transcription factors that may commit levels of transcription factors that may commit them to discrete cell lineages. them to discrete cell lineages.

Which cell lineage is selected for differentiation Which cell lineage is selected for differentiation may depend both on chance and on the external may depend both on chance and on the external signals received by progenitor cells. signals received by progenitor cells.

Several transcription factors have been isolated Several transcription factors have been isolated that regulate differentiation along the major cell that regulate differentiation along the major cell lineages. lineages.

For instance, the Ikaros, Aiolos and Helios For instance, the Ikaros, Aiolos and Helios transcription factors play a major role in transcription factors play a major role in lymphoid development.lymphoid development.

HAEMATOPOIESIS – HAEMATOPOIESIS – RBCsRBCs

Characteristics seen in Characteristics seen in erythrocytes during erythrocytes during

erythropoiesiserythropoiesisThe following characteristics can be seen changing in the The following characteristics can be seen changing in the

erythrocytes when they are maturing:erythrocytes when they are maturing:

They show a reduction in the cell sizeThey show a reduction in the cell size

The cytoplasmic matrix increases in amountThe cytoplasmic matrix increases in amount

Staining reaction of the cytoplasm changes from basophilic to Staining reaction of the cytoplasm changes from basophilic to acidophilic acidophilic

Initially the nucleus was large in size and contained open Initially the nucleus was large in size and contained open chromatin. But with the maturation of RBC's the size of the chromatin. But with the maturation of RBC's the size of the nucleus decreases and finally disappears with the nucleus decreases and finally disappears with the condensation of the chromatin materialcondensation of the chromatin material