Lineage Specific Hematopoiesis

How do we make sure that progenitor or stem cells are committed

give them growth factors

Review: What are the two theories

1. Monophyletic

2. Polyphyletic

This theory states that all blood cells are from a single progenitor cell

Monophyletic theory

This theory states that every blood cell is derived from its own unique progenitor cell

Polyphyletic theory

• This is a controlled continuous procesz of production of blood cells

• Producing only what the body needs

Hematopoiesis

What is the commonly accepted theory

Monophyletic theory

According to the monophyletic theory, what is the stem cell that gives rise to many other cells

Pluripotent stem cell

• Because of this cell, we can form multiple cells

• Gives rise to 2 progenitor cells

• Follows the monophyletic theory

Pluripotent stem cell (PPSC)

The pluripotent stem cell gives rise to what two progenitor cells

1. Lymphoid stem cell

2. Myeloid stem cell

• Its progenitor cell is the pluripotent stem cell

• Only gives us lymphoctes

• Bone marrow makes B cells

• Thymus T cells

Lymphoid stem cell

• Its progenitor cell is the pluripotent stem cell

• Gives rise to other cells except the lymphocytes

Myeloid stem cell

Poiesis means

Production

Myeloid and lymphoid gives us what

Colony forming units

• This means the production of RBCs/erythrocytes from the myeloid stem cell

• Regulated process for maintaining adequate number of RBCs jn the peripheral blood

• A process by which erythroid precursor cells differentiates to become mature

Erythropoiesis

• This is a glycoprotein hormone

• Primary source are the kidneys

• They stimulate erythropoiesis

• This is a growth factor

• Naturally produced by the peritubular cells of the kidney

Erythropoietin (EPO)

Whenever the body experiences (blank), it sends signals to our kidneys to further release (blank) and once they release it and in turn it will stimulate the progenitor cells to commit themselves jnto producing RBCs

Hypoxia; erythropoietin

What are the two main regulators of Erythropoiesis

1. Kidney

2. Liver

• This is a main regulator of erythropoiesis

• Main source of erythropoiesis

• Specifically, this is in the renal peritubukar interstitial cells

• Helps hematopoiesis in RBC production

Kidney

• This is a main regulatory of erythropoiesis

• This is another source of erythropoietin

• Little amount only (not main)

Liver

• This refers to programmed cell death

• Is normal physiological process that eliminates unwanted, abnormal, or harmful cells

Apoptosis

• Erythropoietin ensures that cells will survive so they prevent (blank)

• This also allows for the immature cells to produce hemoglobin

• Helps RBCs become functional

prevents apoptosis

Are mature blood cells capable of producing Hgb?

No

Only (blank) cells produce Hgb with the help of erythropoietin

Immature

Cells get smaller as they mature because of

Mitosis

As cells mature, the (blank) of the cell changes because of the production of hemoglobin A1

Color

Hemoglobin is made up of

Heme and globin

What is the protein component of hemoglobin

Globin

As the cells mature, their nucleus (blank)

Condenses

The color of the cells as they mature is from (blank) color for basophilic and then gray and then (blank) color for eosinophil

Blue; red

• This is considered as the first recognizable cell

• Will be RBCs in a couple of days

Pronormoblast

• The pluripotential hematopoietic stem cell will form progenitors called (blank) with the help of cytokines

• The first colony to be formed

CFU-GEMM

What does CFU-GEMM mean?

Granulocyte, Erythrocyte, Monocyte, Megakaryocyte

The CFU-GEMM will give rise to the formation of (blank) which are also colonies

BFU Erythroid

What does BFU Erythroid mean?

Burst forming unit

BFU Erythroid have limited number of receptors only so (blank) cannot bind to them

EPO

What are the stimulants that will stimulate the BFU-E to finally mame them bind with EPO

IL-3, TPO, and GMCSF

And because the BFU-E is now stimulated, it will now form what

CFU-E

What does CFU-E stand for?

Colony forming units erythroid

Compared to BFU-E, CFU-E has more (blank) sites for EPO

Binding

BFU-E or CFU-E?

• Larger colonies

• Very few receptors for EPO so others will stimulate it nalang instead of EPO

• Slow to mature

This is BFU-E

BFU-E or CFU-E

• Has smaller colonies

• Plenty of receptors for EPO

• Fast mature rate

This is CFU-E

If we are dealing with colonies, morphologically, they look the (blank)

Same

Since colonies are morphologically the same, and we want to know which colony is which, we use specialized tests like (blank)

Flowcytometry

• This is the most commonly used test to determine the specific type of colony

• We can check here for certain markers, antigens, to help us identify the colony

Flowcytometry test

How long does it take for BFU-E to CFU-E

around 7 days

How long does it take for CFU-E to Pronormoblasts

Another 7 days

How kong does it take for Pronormoblast to be red cell?

4 to 7 days

In total, from CFU to Red cell, how long does it usually take?

18 to 21 days or 3 weeks

• This is the earliest recognizable stage

• Large purple nucleus with a bluish cytoplasm surrounding it

• Hemoglobin is not made yet

• Where they begin to accumulate the components necessary for hemoglobin production

• Undergoes mitosis

Pronormoblast

For 1 pronormoblast, it can produce (blank to blank) RBCs because of mitosis

8 to 32

• This is one of the stages where we start to synthesize Hgb

• Is basophilic as the cytoplasm is insanely blue

• We can 100% detect Hgb in this stage but we cannot see it yet

• Nucleus is centrally located

• Undergoes mitosis

Basophilic normoblast

• This is the stage where many colors are present

• Visible signs of hemoglobin

• Last stage of erythropoiesis to undergo cell division/mitosis

• Still divides here but this is the last divide

• Cytoplasm has pinkish to reddish color

Polychromatic normoblast

• In this stage, the cell no longer divides

• Nucleus is eccentrically located as it is the last stage to have a nucleus

• Since this is the last stage to have a nucleus, it can still make hemoglobin

• Last stage to make hemoglobin

• Location in the bone marrow

Orthochromic normoblast

In orthochromic normoblast, it is the last stage to have a nucleus so it is starting to mature and as they mature, they will lose the unimportant protein (blank)

Vimentin

This is an unimportant protein in orthochromic normoblast which holds all the organelles into place and if we lose this, the nucleus will be extruded

Vimentin protein

When the nucleus js out, that nucleus is called (blank) and has no more purpose

Pyrenocyte

• In this stage, it can still synthesize Hgb because it still has bits of RNA (bluish dots

• They are mature cells but they are an exception to the rule that “mature cells are in the peripheral blood and immature cells are in the bone marrow” as they are mature cells in the peripheral blood but they can still produce Hgb

• They stay in the marrow for 2 days, go out in the blood and stay there for 1 day, and after 1 day, they become red cells

Reticulocyte

If reticulocytes are released earlier than normal is called

Shift reticulocyte

1/3 of the Hgb are from

From Reticulocytes

• In reticulocytes, we cannot count them so we need this special staining technique

• We use this stain when the reticulocytes are still alive

• Uses methylene blue or brilliant cresil blue

Supravital stain

When should we count reticulocytes?

When we want to see if our bone marrow is responding

• These are what occurs after reticulocytes

• Once we reach this stage, it should have enough Hgb to bind, carry, and transport oxygen

• Lives for 120 days

Erythrocytes

• This refers to the WBC production in the body

• WBC can either be lymphocyte, granulocyte, and monocyte

Leukopoiesis

What are the two divisions of leukopoiesis

Hint: ML

1. Myelopoiesis

2. Lymphopoiesis

For granulopoiesis, what are the 3 granulocytes we have

Hint: BEN

1. Basophils

2. Eosinophils

3. Neutrophils

Granulocytes are called that because they have (blank) which helps them kill

Granules

Neutrophils share the same progenitor with

Monocytes

What are the main stimulants for neutrophil development for neutrophil

Granulocyte Colony Stimulating Factor or GCSF

What are the main stimulants for neutrophil development for monocyte

Monocyte colony stimulating factor or Monocyte

If we use GCSF, it will give us what

Neutrophil

If we use M-CSF, we will have what

Monocytes

What are the three stages of neutrophil development

1. Stem cell pool

2. Proliferation pool

3. Maturation pool

• This is a stage in neutrophil development

• We only see stem cells

Stem cell pool

• This is a stage of neutrophil development

• Cells are capble of mitosis

• Stage of mitosis

Proliferation pool

• This is a stage of neutrophil development

• Its either eosinophil, basophil, neutrophil

• Myelosblast is present

Maturation pool

In the maturation pool, we see here the earliest and first recognizable cell, what is this cell

Myeloblast

• This is the earliest recognizable stage in granulopoiesis in leukopoiesis

• Granules are not yet observed because the nucleus is too big

• Granules are not yet visible

Myeloblast

• This is a stage in leukopoiesis

• The earliest set of granules are now visible

• Myeloblast is under mitosis

• Granules are primary or non specific granules

• Has nuclear halo that will further help us in identifying this

Promyelocyte

• This is a stage in leukopoiesis

• Occurs after promyelocyte has divided

• Granules are now secondary granules

• Last stage to undergo mitosis

Myelocyte

• This is a stage in leukopoiesis

• Tertiary granules starts to appear ans starts being synthesized

• Does not divide anymore as it is not capable

• “Kidney-bean” shaped nucleus

• Maturation phase

Metamyelocyte

• This is the last stage in leukopoiesis

• Secratory granules are present

• Exception in the rule like reticulocytes

• Nucleus is not segmented

Band cell

If we are not sure wheter it is a band cell or a neutrophil, count it as a what

Neutrophil

• This is a matured band cell

• Most abundant neutrophil in the bloof

• This is the half-life of neutrophils

• Has segments or lobes

Segemnted neutrophils

What is the half life of eosinophil

18 hours

How long will eosinophil last in the tissue

2 to 5 days

• This causes being critical in parasitism because of their granules in eosinophil development

• This is a major basic protein

Charcot leyden crystals

• These leukocytes are closely related to mast cells (develop in the tissue)

• The littlest amount of leukocytes as we only need this in times of hypersensitivity

• Derived from the progenitors of bone marrow and spleen

• Immature and present in the bone marrow

Basophil

Basophil is dependent on what two?

1. IL-3-IgE dependent

2. TSLP non-IgE dependent

What are the major basic proteins of basophil

IL, TLSP, IgE

• This is the largest cell in the blood

• Share the same progenitor as neutrophil but different growth factor

• Seen in the blood

• Kidney bean or horse shoe shaped nucleus

• Cytoplasm has vacuoles

Monocytes

What are the three stages or main stimulants for monocyte development

1. Monoblast

2. Promonocyte

3. Monocyte

Once the monocyte leaves for the tissues, it will now be called a blank

Macrophage

Does the monocyte count if it has vacuoles?

No

To differentiate lymphocytes, ws use what

CD markers or antigen testing

Antigen independent lymphocytes are produced (blank) stimulation

Without

Antigen dependent lymphocytes are produced (blank) stimulation

With

These are cells that has not been exposed to an antigen

Naive or resting lymphocytes

What are the 3 types of B cells

1. Pro-B

2. Pre-B

3. Immature B cells

What are the three types of T cells

1. Pro-T

2. Pre-T

3. Immature T cell

Which of these T cells are stimulated

B and C