Blood physiology Leta hematology system ppt
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Aug 28, 2024
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About This Presentation
hematology system
Slide Content
College of Health Sciences
Department of Biomedical Science
Blood
Physiolog
y
“Fluid of Life”
“Fluid of Growth”
“Fluid of Health”
Slide 1
Department of Biomedical Science
Blood
Physiolog
y
“Fluid of Life”
“Fluid of Growth”
“Fluid of Health”
Slide 1
•Most cells of a multicellular organism cannot move around.
Needs are met by blood and interstitial fluid.
•Blood is a liquid connective tissue that consists of cells
surrounded by a liquid extracellular matrix.
•Blood is considered a connective tissue, due to
Anatomically – origin in the bones and
Physiologically – function.
Introduction
Slide 2
Needs are met by blood and interstitial fluid.
•Blood is a liquid connective tissue that consists of cells
surrounded by a liquid extracellular matrix.
•Blood is considered a connective tissue, due to
Anatomically – origin in the bones and
Physiologically – function.
Introduction
Slide 2
Color varies from bright red to dark red.
It has a slightly alkaline – pH 7.35 – 7.45.
Its temperature is 38
0
C
It constitutes about 20% of ECF – osmolarity = 300 mOsm.
It is amounting to 8% of the total body mass.
It is denser and more viscous than water and feels
slightly sticky – It’s viscosity is 3-4 than that of water.
Physical Characteristics And Volume of Blood
Slide 3
It has a slightly alkaline – pH 7.35 – 7.45.
Its temperature is 38
0
C
It constitutes about 20% of ECF – osmolarity = 300 mOsm.
It is amounting to 8% of the total body mass.
It is denser and more viscous than water and feels
slightly sticky – It’s viscosity is 3-4 than that of water.
Physical Characteristics And Volume of Blood
Slide 3
Density (Specific gravity) – 1 ml of whole blood weighing
1.052 to 1.061 gm.
oMale: 1.052 - 1.063 and Female: 1.050 - 1.058
Its volume is 5–6 L - males, and 4–5 L – females and 450
ml – newborn baby.
oTotal blood volume is 70 mL/kg body weight in the
adult woman and 80 mL/kg in the adult man.
Salinity = 0.85% – reflects [NaCl] in the blood
All tissues have no equal blood supply.
Cont’d…
Slide 4
1.052 to 1.061 gm.
oMale: 1.052 - 1.063 and Female: 1.050 - 1.058
Its volume is 5–6 L - males, and 4–5 L – females and 450
ml – newborn baby.
oTotal blood volume is 70 mL/kg body weight in the
adult woman and 80 mL/kg in the adult man.
Salinity = 0.85% – reflects [NaCl] in the blood
All tissues have no equal blood supply.
Cont’d…
Slide 4
•The functions of the blood can be :-
Transportation –
oRespiratory gases.
oNutrient.
oHormones.
oExcretory products.
oHeat.
Functions of Blood
Slide 5
Transportation –
oRespiratory gases.
oNutrient.
oHormones.
oExcretory products.
oHeat.
Functions of Blood
Slide 5
Regulation.
oFluid volume in circulatory system.
oHormonal.
oTemperature.
opH.
Protection.
oAgainst blood loss from injury – clotting mechanism.
oAgainst pathogens – immune system.
Cont’d…
Slide 6
oFluid volume in circulatory system.
oHormonal.
oTemperature.
opH.
Protection.
oAgainst blood loss from injury – clotting mechanism.
oAgainst pathogens – immune system.
Cont’d…
Slide 6
Blood Composition
•Blood is a sticky, opaque fluid with metallic taste with the
circulating portion of ECF.
•Whole blood has two components:
i.Blood plasma – watery liquid extracellular matrix that
contains dissolved substances.
It makes up 55% of blood volume.
ii.Formed elements – cells and cell fragments.
Make the remaining (45%) blood volume.
Slide 7
•Blood is a sticky, opaque fluid with metallic taste with the
circulating portion of ECF.
•Whole blood has two components:
i.Blood plasma – watery liquid extracellular matrix that
contains dissolved substances.
It makes up 55% of blood volume.
ii.Formed elements – cells and cell fragments.
Make the remaining (45%) blood volume.
Slide 7
oNormally, ~ 99% of the
formed elements – red
blood cells (RBCs).
•If a sample of blood
containing an anticoagulant
is centrifuged (spun) in a
small glass tube for ~5
minutes at 10,000 revolution.
•Generally, there are two
types of centrifuges:
The filtration and
sedimentation
centrifuges.
Cont’d…
Slide 8
formed elements – red
blood cells (RBCs).
•If a sample of blood
containing an anticoagulant
is centrifuged (spun) in a
small glass tube for ~5
minutes at 10,000 revolution.
•Generally, there are two
types of centrifuges:
The filtration and
sedimentation
centrifuges.
Cont’d…
Slide 8
Blood Plasma
•Plasma is a straw-colored clear liquid part of blood that
accounts for 55% of TBV and has the osmolality 300 mosm/L.
Occur after the formed elements are removed.
•It contains:
Water – about 90% of the plasma
Plasma proteins – about 7-9% and
Small dissolved solutes (1-3%) – hormones, enzymes,
nutrient molecules, gases, electrolytes etc.
Slide 9
•Plasma is a straw-colored clear liquid part of blood that
accounts for 55% of TBV and has the osmolality 300 mosm/L.
Occur after the formed elements are removed.
•It contains:
Water – about 90% of the plasma
Plasma proteins – about 7-9% and
Small dissolved solutes (1-3%) – hormones, enzymes,
nutrient molecules, gases, electrolytes etc.
Slide 9
•The principal – albumin, fibrinogen and globulins –
molecular masses.
•Electrophoresis can be used to fractionate plasma proteins.
The electrophoretic mobility of a protein depends on its
molecular weight (size and shape) as well as its electrical
charge.
oIn decreasing order – albumin, α
1-globulins, α
2-
globulins, β-globulins, fibrinogen, and γ-globulins.
Plasma Proteins
Slide 10
molecular masses.
•Electrophoresis can be used to fractionate plasma proteins.
The electrophoretic mobility of a protein depends on its
molecular weight (size and shape) as well as its electrical
charge.
oIn decreasing order – albumin, α
1-globulins, α
2-
globulins, β-globulins, fibrinogen, and γ-globulins.
Plasma Proteins
Slide 10
•It is the smallest and most numerous plasma protein.
•The plasma concentration – ranges from 3.5 to 5.5 g/dL.
Providing the body with a total plasma albumin pool of
~135 g.
•It is synthesized by the liver at a rate of ~120 mg/kg body
weight per day.
Because of catabolism, it has a half-life in the circulation
of ~20 days.
Albumin
Slide 11
•The plasma concentration – ranges from 3.5 to 5.5 g/dL.
Providing the body with a total plasma albumin pool of
~135 g.
•It is synthesized by the liver at a rate of ~120 mg/kg body
weight per day.
Because of catabolism, it has a half-life in the circulation
of ~20 days.
Albumin
Slide 11
Urinary losses are normally negligible (<20 mg/day).
•An important function of albumin –
Serve as a carrier protein – transporting – hormones,
amino acids, fatty acids, bile salts and vitamins.
Serve as an important blood buffer,
Serves as an osmotic regulator – maintain blood volume
and pressure.
oAccount for 80% of the total colloid osmotic pressure
or oncotic pressure (~25 mm Hg).
Cont’d…
Slide 12
•An important function of albumin –
Serve as a carrier protein – transporting – hormones,
amino acids, fatty acids, bile salts and vitamins.
Serve as an important blood buffer,
Serves as an osmotic regulator – maintain blood volume
and pressure.
oAccount for 80% of the total colloid osmotic pressure
or oncotic pressure (~25 mm Hg).
Cont’d…
Slide 12
•It account for about 38% of plasma proteins.
•The three types of globulins are alpha, beta, and gamma.
•The alpha and beta globulins are involved –
Transportation.
Function as clotting factors, and
Serve as precursor molecules (angiotensinogen).
Globulins
Slide 13
•The three types of globulins are alpha, beta, and gamma.
•The alpha and beta globulins are involved –
Transportation.
Function as clotting factors, and
Serve as precursor molecules (angiotensinogen).
Globulins
Slide 13
•Important examples of transport globulins –
i.Hormone-binding proteins – provide a reserve of hormones
in the bloodstream.
Thyroid-binding globulin and transthyretin – transport
TH and
Transcortin – transports ACTH.
ii.Metalloproteins – transport metal ions.
Transferrin – transports iron (Fe
2+
).
iii.Apolipoproteins – carry triglycerides and other lipids.
Cont’d…
Slide 14
i.Hormone-binding proteins – provide a reserve of hormones
in the bloodstream.
Thyroid-binding globulin and transthyretin – transport
TH and
Transcortin – transports ACTH.
ii.Metalloproteins – transport metal ions.
Transferrin – transports iron (Fe
2+
).
iii.Apolipoproteins – carry triglycerides and other lipids.
Cont’d…
Slide 14
When bound to lipids in blood, an apolipoprotein
becomes a lipoprotein.
iv.Steroid-binding proteins – transport steroid hormones in
blood.
Testosterone-binding globulin (TeBG) binds and
transports testosterone.
•The gamma globulins (antibodies) are released by plasma
cells during immune response.
•γ-globulins (immunoglobulins or antibodies): can be
separated into 5 types.
Cont’d…
Slide 15
becomes a lipoprotein.
iv.Steroid-binding proteins – transport steroid hormones in
blood.
Testosterone-binding globulin (TeBG) binds and
transports testosterone.
•The gamma globulins (antibodies) are released by plasma
cells during immune response.
•γ-globulins (immunoglobulins or antibodies): can be
separated into 5 types.
Cont’d…
Slide 15
Slide 16
•All antibodies are different
based on their
Amino acid sequence in the
constant region,
Structure (monomer,
pentamer, and dimer),
Short-life in the blood,
Site, and
Immunological properties.
Cont’d…
•All antibodies are different
based on their
Amino acid sequence in the
constant region,
Structure (monomer,
pentamer, and dimer),
Short-life in the blood,
Site, and
Immunological properties.
Cont’d…
Slide 17
•IgG is the most common and abundant antibody present in
the body.
Blood plasma consists of 75-80% of IgG antibodies.
Of all antibodies, IgG has the longest lifespan of about 23
days.
•IgG is the only antibody that can cross the placental barrier
and provide passive immunity to a developing fetus.
•IgG antibodies remember the pathogens that have
previously entered the body and caused an infection.
a)Immunoglobulins G (IgG)
Cont’d…
•IgG is the most common and abundant antibody present in
the body.
Blood plasma consists of 75-80% of IgG antibodies.
Of all antibodies, IgG has the longest lifespan of about 23
days.
•IgG is the only antibody that can cross the placental barrier
and provide passive immunity to a developing fetus.
•IgG antibodies remember the pathogens that have
previously entered the body and caused an infection.
a)Immunoglobulins G (IgG)
Cont’d…
Slide 18
•IgG also provides some immunity to infants when ingested
through breast milk.
•The function of IgG is to
Enhance the phagocytosis of pathogens,
Neutralize bacterial or viral toxins, and
Trigger the activation of the complement system.
•IgG has four isotypes:
IgG1, IgG2, IgG3, IgG4
Cont’d…
•IgG also provides some immunity to infants when ingested
through breast milk.
•The function of IgG is to
Enhance the phagocytosis of pathogens,
Neutralize bacterial or viral toxins, and
Trigger the activation of the complement system.
•IgG has four isotypes:
IgG1, IgG2, IgG3, IgG4
Cont’d…
Slide 19
•IgM is the first antibody that interacts with new bacteria that
enters the body, and it initiates a primary immune response.
IgM is also called a natural antibody because it serves as
the first line of defense of the immune system and
provides short-term protection.
•IgM has a gigantic pentamer structure above all other
antibodies and consists of 10 antigen-binding sites, making
them more effective than IgG in killing bacteria or viruses.
b)Immunoglobulin M (IgM)
Cont’d…
•IgM is the first antibody that interacts with new bacteria that
enters the body, and it initiates a primary immune response.
IgM is also called a natural antibody because it serves as
the first line of defense of the immune system and
provides short-term protection.
•IgM has a gigantic pentamer structure above all other
antibodies and consists of 10 antigen-binding sites, making
them more effective than IgG in killing bacteria or viruses.
b)Immunoglobulin M (IgM)
Cont’d…
Slide 20
•The life span of the IgM antibody is about five days.
It makes up 5-10% of the antibodies in blood plasma.
•IgM also causes agglutination (formation of clumps) of
bacteria when binding to its surface epitope.
The IgM antibody is known as a potent agglutinin and is
also found on the surface of naïve B-cells and red blood
cells in its monomeric form.
Cont’d…
•The life span of the IgM antibody is about five days.
It makes up 5-10% of the antibodies in blood plasma.
•IgM also causes agglutination (formation of clumps) of
bacteria when binding to its surface epitope.
The IgM antibody is known as a potent agglutinin and is
also found on the surface of naïve B-cells and red blood
cells in its monomeric form.
Cont’d…
Slide 21
•IgA is the most common antibody after IgG.
•IgA is present in the blood, lymph, and other body
secretions such as saliva, tears, and milk.
It can also be found in the genital lining, respiratory tract,
and intestine lining.
•IgA antibodies protect the body from bacterial growth and
colonization.
c)Immunoglobulins A (IgA)
Cont’d…
•IgA is the most common antibody after IgG.
•IgA is present in the blood, lymph, and other body
secretions such as saliva, tears, and milk.
It can also be found in the genital lining, respiratory tract,
and intestine lining.
•IgA antibodies protect the body from bacterial growth and
colonization.
c)Immunoglobulins A (IgA)
Cont’d…
Slide 22
However, it is less stable than IgG and can be found in a
lower quantity, accounting for about 10-15% of the total
immunoglobulins in the blood.
•IgA is often called a secretory antibody because it has an
attached secretory component that protects it from enzymatic
digestion.
•Every day, a human secretes about 5 g to 15 g of secretory
IgA into mucous secretions to prevent pathogenesis.
Cont’d…
However, it is less stable than IgG and can be found in a
lower quantity, accounting for about 10-15% of the total
immunoglobulins in the blood.
•IgA is often called a secretory antibody because it has an
attached secretory component that protects it from enzymatic
digestion.
•Every day, a human secretes about 5 g to 15 g of secretory
IgA into mucous secretions to prevent pathogenesis.
Cont’d…
Slide 23
•IgD makes up less than 0.5% of serum antibodies.
•IgD is found in lesser amounts in lymphatic fluids and
blood.
•The function of IgD is still unknown,
But it is present on the surface of immature B-cells as
receptors, and it is also a part of the innate immune
system.
Researchers believe that IgD regulates the B-cells’
activation and differentiation into plasma cells.
d)Immunoglobulins D (IgD)
Cont’d…
•IgD makes up less than 0.5% of serum antibodies.
•IgD is found in lesser amounts in lymphatic fluids and
blood.
•The function of IgD is still unknown,
But it is present on the surface of immature B-cells as
receptors, and it is also a part of the innate immune
system.
Researchers believe that IgD regulates the B-cells’
activation and differentiation into plasma cells.
d)Immunoglobulins D (IgD)
Cont’d…
Slide 24
•IgE makes up less than 0.01% of serum antibodies and has a
shorter lifespan.
•IgE is the most effective antibody against parasitic
infections, including helminths.
•A high level of IgE in the blood can sometimes cause
hypersensitivity toward non-harmful substances.
Recently, immunologists have begun formulating new
anti-IgE antibodies for the treatment of allergy and
asthma.
e)Immunoglobulins E (IgE)
Cont’d…
•IgE makes up less than 0.01% of serum antibodies and has a
shorter lifespan.
•IgE is the most effective antibody against parasitic
infections, including helminths.
•A high level of IgE in the blood can sometimes cause
hypersensitivity toward non-harmful substances.
Recently, immunologists have begun formulating new
anti-IgE antibodies for the treatment of allergy and
asthma.
e)Immunoglobulins E (IgE)
Cont’d…
•It is a dimer of identical heterotrimers, each composed of Aα,
Bβ, and γ chains.
•It is synthesized only by the liver and circulates in plasma at
concentrations of 150 to 300 mg/dL.
•Function – plays a role in the blood clotting process.
It serves as a precursor for fibrin – forms the meshwork of
a blood clot.
oFibrin threads serve as adhesive in binding platelets, red
blood cells, and other molecules together.
Fibrinogen
Slide 25
Bβ, and γ chains.
•It is synthesized only by the liver and circulates in plasma at
concentrations of 150 to 300 mg/dL.
•Function – plays a role in the blood clotting process.
It serves as a precursor for fibrin – forms the meshwork of
a blood clot.
oFibrin threads serve as adhesive in binding platelets, red
blood cells, and other molecules together.
Fibrinogen
Slide 25
•It is the clear straw-colored fluid that oozes from blood clot.
•When the blood is shed or collected in a container, it clots.
In this process, the fibrinogen is converted into fibrin and
the blood cells are trapped in this fibrin forming the
blood clot.
•After about 45 minutes, serum oozes out of the blood clot.
•For clinical investigations, serum is separated from blood
cells and clotting elements by centrifuging.
Serum
Cont’d…
•When the blood is shed or collected in a container, it clots.
In this process, the fibrinogen is converted into fibrin and
the blood cells are trapped in this fibrin forming the
blood clot.
•After about 45 minutes, serum oozes out of the blood clot.
•For clinical investigations, serum is separated from blood
cells and clotting elements by centrifuging.
Serum
Cont’d…
27
•Volume of the serum is almost the same as that of plasma
(55%).
•Serum contains all the other constituents of plasma except
fibrinogen.
Because fibrinogen is converted into fibrin during blood
clotting.
Serum = Plasma – Fibrinogen
Cont’d…
•Volume of the serum is almost the same as that of plasma
(55%).
•Serum contains all the other constituents of plasma except
fibrinogen.
Because fibrinogen is converted into fibrin during blood
clotting.
Serum = Plasma – Fibrinogen
Cont’d…
i.Role In Coagulation Of Blood: Fibrinogen is essential.
ii.Role In Defense Mechanism Of Body: gamma globulins play
an important role.
iii.Role In Transport Mechanism: albumin, alpha globulin and
beta globulin are responsible.
iv.Role In Maintenance Of Osmotic Pressure In Blood
Since the concentration of albumin is more than the other
plasma proteins, it exerts maximum pressure.
Globulin is the next and fibrinogen exerts least pressure.
Functions Of Plasma Proteins
ii.Role In Defense Mechanism Of Body: gamma globulins play
an important role.
iii.Role In Transport Mechanism: albumin, alpha globulin and
beta globulin are responsible.
iv.Role In Maintenance Of Osmotic Pressure In Blood
Since the concentration of albumin is more than the other
plasma proteins, it exerts maximum pressure.
Globulin is the next and fibrinogen exerts least pressure.
Functions Of Plasma Proteins
v.Role In Regulation Of Acid-base Balance
Plasma proteins, particularly the albumin, play an
important role.
Plasma proteins are responsible for 15% of the buffering
capacity of blood.
vi.Role In Viscosity Of Blood: albumin provides maximum
viscosity than the other plasma proteins.
vii.Role In Erythrocyte Sedimentation Rate: globulin and
fibrinogen accelerate the tendency of rouleaux formation,
which is responsible for ESR.
Cont’d…
Plasma proteins, particularly the albumin, play an
important role.
Plasma proteins are responsible for 15% of the buffering
capacity of blood.
vi.Role In Viscosity Of Blood: albumin provides maximum
viscosity than the other plasma proteins.
vii.Role In Erythrocyte Sedimentation Rate: globulin and
fibrinogen accelerate the tendency of rouleaux formation,
which is responsible for ESR.
Cont’d…
viii.Role In Suspension Stability Of Red Blood Cells
During circulation, the red blood cells remain suspended
uniformly in the blood.
Globulin and fibrinogen help in the suspension stability.
ix.Role In Production Of Trephone Substances: produced by
leukocytes from the plasma proteins.
x.Role As Reserve Proteins: during fasting, inadequate food
intake or inadequate protein intake, the plasma proteins
are utilized by the body tissues as the last source of
energy.
Cont’d…
During circulation, the red blood cells remain suspended
uniformly in the blood.
Globulin and fibrinogen help in the suspension stability.
ix.Role In Production Of Trephone Substances: produced by
leukocytes from the plasma proteins.
x.Role As Reserve Proteins: during fasting, inadequate food
intake or inadequate protein intake, the plasma proteins
are utilized by the body tissues as the last source of
energy.
Cont’d…
•Include: -
Erythrocytes, or red blood cells (RBCs)
Leukocytes, or white blood cells (WBCs)
Thrombocytes, or platelets
•RBCs and WBCs are whole cells; platelets are cell fragments.
RBCs and platelets have just a few roles, but WBCs have
a number of specialized functions.
Formed Elements
Slide 31
Erythrocytes, or red blood cells (RBCs)
Leukocytes, or white blood cells (WBCs)
Thrombocytes, or platelets
•RBCs and WBCs are whole cells; platelets are cell fragments.
RBCs and platelets have just a few roles, but WBCs have
a number of specialized functions.
Formed Elements
Slide 31
Red Blood Cell
•It account for 99.9%: most numerous of the cellular elements.
Whole blood contains about 1000 RBCs for each WBCs.
•Give whole blood its deep red color.
•RBC count – number of RBCs per microliter of whole blood.
Adult males, 1 μL of blood contains 4.5–6.3 million RBCs.
Adult females, 1 μL contains 4.2–5.5 million.
A single drop of blood contains ~ 260 million RBCs.
Slide 32
•It account for 99.9%: most numerous of the cellular elements.
Whole blood contains about 1000 RBCs for each WBCs.
•Give whole blood its deep red color.
•RBC count – number of RBCs per microliter of whole blood.
Adult males, 1 μL of blood contains 4.5–6.3 million RBCs.
Adult females, 1 μL contains 4.2–5.5 million.
A single drop of blood contains ~ 260 million RBCs.
Slide 32
•Hematocrit or packed cell volume (PCV) – the percentage of a
blood volume that consists of RBCs.
•An average hematocrit is about 45%.
Males: 47 + 5%
Females: 42 + 5%
•The viscosity of the blood is determined primarily by these
elements.
•Remember Hgb = 1/3 Hct.
Cont’d…
Slide 33
blood volume that consists of RBCs.
•An average hematocrit is about 45%.
Males: 47 + 5%
Females: 42 + 5%
•The viscosity of the blood is determined primarily by these
elements.
•Remember Hgb = 1/3 Hct.
Cont’d…
Slide 33
•Normally, the RBCs are nonnucleated biconcave (dumbbell
shaped).
Central portion is thinner and periphery is thicker.
•An average diameter of RBC is 7.5 μm with a maximum
thickness of 2.85 μm, although the center narrows to
about 0.8 μm.
Surface area : 120 sq μm.
Volume : 85 to 90 cu μm.
Structure of RBCs
Slide 34
shaped).
Central portion is thinner and periphery is thicker.
•An average diameter of RBC is 7.5 μm with a maximum
thickness of 2.85 μm, although the center narrows to
about 0.8 μm.
Surface area : 120 sq μm.
Volume : 85 to 90 cu μm.
Structure of RBCs
Slide 34
•The unusual shape has 3 important effects on RBC function:
1.Giving Each RBC a Large Surface-Area-to-Volume Ratio.
Maximizing diffusion area and minimizing intracellular
diffusion distances for gas exchange.
oIt maximizes the surface area – 30%.
•The total surface area of all the RBCs in the blood of a
typical adult is about 3800 square meters.
2000 times the total surface area of the body.
Cont’d…
Slide 35
1.Giving Each RBC a Large Surface-Area-to-Volume Ratio.
Maximizing diffusion area and minimizing intracellular
diffusion distances for gas exchange.
oIt maximizes the surface area – 30%.
•The total surface area of all the RBCs in the blood of a
typical adult is about 3800 square meters.
2000 times the total surface area of the body.
Cont’d…
Slide 35
2.Enabling RBCs to Form Stacks That Smooth the Flow through
Narrow Blood Vessels.
•When the RBCS are observed under microscope, they pile up
one above another like the pile of coins.
These stacks, known as rouleaux, form and dissociate
repeatedly without affecting the cells involved.
•An entire stack can pass along a blood vessel that is only
slightly larger than the diameter of a single RBC.
Whereas individual cells would bump the walls, bang
together, and form logjams that could prevent blood flow.
Cont’d…
Slide 36
Narrow Blood Vessels.
•When the RBCS are observed under microscope, they pile up
one above another like the pile of coins.
These stacks, known as rouleaux, form and dissociate
repeatedly without affecting the cells involved.
•An entire stack can pass along a blood vessel that is only
slightly larger than the diameter of a single RBC.
Whereas individual cells would bump the walls, bang
together, and form logjams that could prevent blood flow.
Cont’d…
Slide 36
Cont’d…
Slide 37
Slide 37
3.Enabling RBCs to Bend and Flex When Entering Small
Capillaries and Branches.
•RBCS are very flexible – squeeze through capillaries as
narrow as 4 μm.
•RBCs retain only the cytoskeleton that is anchored to the
plasma membrane by glycophorin and the Cl-HCO
3
exchanger AE1.
•RBCs membrane has a special type of cytoskeleton, which is
made up of actin and spectrin.
Spectrin give erythrocytes their flexibility.
Cont’d…
Slide 38
Capillaries and Branches.
•RBCS are very flexible – squeeze through capillaries as
narrow as 4 μm.
•RBCs retain only the cytoskeleton that is anchored to the
plasma membrane by glycophorin and the Cl-HCO
3
exchanger AE1.
•RBCs membrane has a special type of cytoskeleton, which is
made up of actin and spectrin.
Spectrin give erythrocytes their flexibility.
Cont’d…
Slide 38
Slide 39
•Other characteristics of RBC are:-
1.Mature RBCs contain no nucleus or intracellular organelles.
Their life span is relatively short— normally 120 days.
No mitochondria - the RBC can engage in two metabolic
pathways –
oGlycolysis – consumes 90% of glucose uptake; and
oPentose shunt – consumes the remaining 10% of
glucose.
Cont’d…
Slide 40
1.Mature RBCs contain no nucleus or intracellular organelles.
Their life span is relatively short— normally 120 days.
No mitochondria - the RBC can engage in two metabolic
pathways –
oGlycolysis – consumes 90% of glucose uptake; and
oPentose shunt – consumes the remaining 10% of
glucose.
Cont’d…
Slide 40
2.RBCs use DPG mutase to convert 1, 3-diphosphoglycerate
into 2, 3-DPG.
2, 3-DPG acts by reducing O
2
affinity of hemoglobin.
3.Erythrocytes contain glutathione at ~2 mM, more than any
other cell of the body outside the hepatocyte.
A high ratio of reduced glutathione (GSH) to oxidized
glutathione (GSSG) protects RBC against oxidant
damage.
Glutathione reductase regenerates GSH from GSSG in a
reaction that consumes NADPH.
Cont’d…
Slide 41
into 2, 3-DPG.
2, 3-DPG acts by reducing O
2
affinity of hemoglobin.
3.Erythrocytes contain glutathione at ~2 mM, more than any
other cell of the body outside the hepatocyte.
A high ratio of reduced glutathione (GSH) to oxidized
glutathione (GSSG) protects RBC against oxidant
damage.
Glutathione reductase regenerates GSH from GSSG in a
reaction that consumes NADPH.
Cont’d…
Slide 41
4.RBCs carry two cytoplasmic isoforms of carbonic anhydrase,
CA I and CA II.
Rapidly interconvert CO
2
and HCO
3
– play a critical role
in transportation of CO
2.
CA II has one of the fastest known enzymatic turnover
rates.
5.AE1 is the most abundant membrane protein in RBCs.
Transport as many as 50,000 ions per second—one of the
fastest known transporters.
Cont’d…
Slide 42
CA I and CA II.
Rapidly interconvert CO
2
and HCO
3
– play a critical role
in transportation of CO
2.
CA II has one of the fastest known enzymatic turnover
rates.
5.AE1 is the most abundant membrane protein in RBCs.
Transport as many as 50,000 ions per second—one of the
fastest known transporters.
Cont’d…
Slide 42
6.AQP1 is the 2
nd
most abundant membrane protein in RBCs.
7.Certain glycolipids in the plasma membrane of RBCs are
antigens that account for the various blood groups.
8.Filled with Hb - 97% of cell contents – gas transport.
•Three features make for efficient gas transport:
Biconcave shape
Having 97% of cell volume filled with hemoglobin
Having no mitochondria
Cont’d…
Slide 43
nd
most abundant membrane protein in RBCs.
7.Certain glycolipids in the plasma membrane of RBCs are
antigens that account for the various blood groups.
8.Filled with Hb - 97% of cell contents – gas transport.
•Three features make for efficient gas transport:
Biconcave shape
Having 97% of cell volume filled with hemoglobin
Having no mitochondria
Cont’d…
Slide 43
•The primary function – transport hemoglobin to the tissues.
Hemoglobin normal values – 13–18 g/100 ml in adult
males, and 12–16 g/100 ml in adult females.
•Hemoglobin is contained in RBCs to prevents it –
From breaking into fragments that would leak out of the
bloodstream and
From making blood more viscous and raising osmotic
pressure.
Function of RBC
Slide 44
Hemoglobin normal values – 13–18 g/100 ml in adult
males, and 12–16 g/100 ml in adult females.
•Hemoglobin is contained in RBCs to prevents it –
From breaking into fragments that would leak out of the
bloodstream and
From making blood more viscous and raising osmotic
pressure.
Function of RBC
Slide 44
•Function of hemoglobin:-
Transportation of gases – O
2
, CO
2
CO and NO gases.
It is a buffer to maintains acid-base balances
•Hemoglobin has two parts: -
Globin part – protein made up of four highly folded
polypeptide chains
Heme group: Fe
2+
containing central part to which O
2
binds.
Cont’d…
Slide 45
Transportation of gases – O
2
, CO
2
CO and NO gases.
It is a buffer to maintains acid-base balances
•Hemoglobin has two parts: -
Globin part – protein made up of four highly folded
polypeptide chains
Heme group: Fe
2+
containing central part to which O
2
binds.
Cont’d…
Slide 45
Cont’d…
Slide 46
•Hemoglobin consists of red
heme pigment bound to the
protein globin.
•Each RBC contains
approximately 280 million
hemoglobin (Hb) molecules.
Each RBC – each
polypeptide has one
heme group, each heme
with Fe
2+
carries one O
2
molecule, total = 4-O
2.
Slide 46
•Hemoglobin consists of red
heme pigment bound to the
protein globin.
•Each RBC contains
approximately 280 million
hemoglobin (Hb) molecules.
Each RBC – each
polypeptide has one
heme group, each heme
with Fe
2+
carries one O
2
molecule, total = 4-O
2.
•O
2
loading in lung: when O
2
binds to iron of the Hb produces
oxyhemoglobin, and becomes ruby red.
•O
2 unloading in tissues: when O
2 detaches from iron and Hb
resumes its former shape results in deoxyhemoglobin, or
reduced hemoglobin and becomes dark red.
•CO
2
loading in tissues: when CO
2
in blood binds to Hb,
produces carbaminohemoglobin.
•A variety of globin chains can be present.
Normally, the alpha and beta (and to a lesser extent the
delta) globin chains form adult hemoglobin.
Cont’d…
Slide 47
2
loading in lung: when O
2
binds to iron of the Hb produces
oxyhemoglobin, and becomes ruby red.
•O
2 unloading in tissues: when O
2 detaches from iron and Hb
resumes its former shape results in deoxyhemoglobin, or
reduced hemoglobin and becomes dark red.
•CO
2
loading in tissues: when CO
2
in blood binds to Hb,
produces carbaminohemoglobin.
•A variety of globin chains can be present.
Normally, the alpha and beta (and to a lesser extent the
delta) globin chains form adult hemoglobin.
Cont’d…
Slide 47
In fetal life, the
gamma, epsilon,
and zeta chains are
present.
•The globin determines
the physical
characteristics of the
Hb-molecule.
Cont’d…
gamma, epsilon,
and zeta chains are
present.
•The globin determines
the physical
characteristics of the
Hb-molecule.
Cont’d…
49
•The various forms of
hemoglobin are
named according to
the types of globin
chains present.
Sickle cell anemia
(Hb-S) – valine is
replaced by glutamic
acid at beta- chain.
Cont’d…
•The various forms of
hemoglobin are
named according to
the types of globin
chains present.
Sickle cell anemia
(Hb-S) – valine is
replaced by glutamic
acid at beta- chain.
Cont’d…
Cont’d…
Slide 50
•About 20% of the CO
2
transported in the blood
combines with hemoglobin.
But it binds to globin’s
amino acids rather than
to the heme group.
This formation of
carbaminohemoglobin
occurs more readily
when hemoglobin is in
the reduced state.
Slide 50
•About 20% of the CO
2
transported in the blood
combines with hemoglobin.
But it binds to globin’s
amino acids rather than
to the heme group.
This formation of
carbaminohemoglobin
occurs more readily
when hemoglobin is in
the reduced state.
•The RBC have other functions besides transport of
hemoglobin.
i.In the maintenance of acid
-base balance: they contain a
large quantity of carbonic anhydrase.
ii.RBCs carry the blood group antigens like A antigen, B
antigen and Rh factor.
This helps in determination of blood group and
enables to prevent reactions due to incompatible
blood transfusion.
Cont’d…
Slide 51
hemoglobin.
i.In the maintenance of acid
-base balance: they contain a
large quantity of carbonic anhydrase.
ii.RBCs carry the blood group antigens like A antigen, B
antigen and Rh factor.
This helps in determination of blood group and
enables to prevent reactions due to incompatible
blood transfusion.
Cont’d…
Slide 51
•Old RBCs become fragile, and Hb begins to degenerates.
•Macrophages engulf and breakdown dying RBCs.
Also detect and remove Hb from ruptured RBCs.
•Macrophages – liver, spleen and BM play a role in recycling
RBC components.
•When old RBCs are broken down and their Hb is released.
Then Hb is phagocytized almost immediately by
macrophages and it is degraded into –
Fate and destruction of Erythrocytes
Slide 52
•Macrophages engulf and breakdown dying RBCs.
Also detect and remove Hb from ruptured RBCs.
•Macrophages – liver, spleen and BM play a role in recycling
RBC components.
•When old RBCs are broken down and their Hb is released.
Then Hb is phagocytized almost immediately by
macrophages and it is degraded into –
Fate and destruction of Erythrocytes
Slide 52
i.The globin part:- amino acid components, which in turn
is recycled by the body.
ii.The heme portion which is again breakdown –
A.The iron – carried by transferrin.
B.The porphyrin portion – removed from the body.
The porphyrin portion converted to biliverdin, an
organic compound with a green color.
Biliverdin is then converted to bilirubin, and
released into the bloodstream.
Cont’d…
Slide 53
is recycled by the body.
ii.The heme portion which is again breakdown –
A.The iron – carried by transferrin.
B.The porphyrin portion – removed from the body.
The porphyrin portion converted to biliverdin, an
organic compound with a green color.
Biliverdin is then converted to bilirubin, and
released into the bloodstream.
Cont’d…
Slide 53
There, the bilirubin binds to albumin and is
transported to the liver for excretion in bile.
In the intestine, bacteria convert bilirubin to related
pigments called urobilinogens and stercobilinogens.
Cont’d…
Slide 54
•Iron is essential for hemoglobin synthesis.
Roughly 26 mg of iron is incorporated into new Hb
molecules each day.
•The total quantity of iron in the body averages 4 to 5 grams.
~ 65% of the body’s iron supply is in hemoglobin.
Iron
transported to the liver for excretion in bile.
In the intestine, bacteria convert bilirubin to related
pigments called urobilinogens and stercobilinogens.
Cont’d…
Slide 54
•Iron is essential for hemoglobin synthesis.
Roughly 26 mg of iron is incorporated into new Hb
molecules each day.
•The total quantity of iron in the body averages 4 to 5 grams.
~ 65% of the body’s iron supply is in hemoglobin.
Iron
15-30% Fe stored in the liver and spleen in the form of
ferritin.
oAnd to a much lesser extent is stored bone marrow.
Small amounts of iron are lost each day in feces, urine,
and perspiration.
oThe average daily loss of iron is 1.7 mg in women and
0.9 mg in men.
oIn women, the menstrual flow accounts for the
additional losses.
Slide 55
Cont’d…
ferritin.
oAnd to a much lesser extent is stored bone marrow.
Small amounts of iron are lost each day in feces, urine,
and perspiration.
oThe average daily loss of iron is 1.7 mg in women and
0.9 mg in men.
oIn women, the menstrual flow accounts for the
additional losses.
Slide 55
Cont’d…
Slide 56
•Iron is absorbed from small intestine in bound form with β
globulin, apotransferrin.
Combination of apotransferrin with iron forms
transferrin.
•Transferrin binds with receptors in the membranes of the
intestinal epithelial cells.
•Transferrin is absorbed (by pinocytosis) into the epithelial
cells and later released into the blood capillaries in the form
of plasma transferrin.
Iron Absorption and Transport
Cont’d…
•Iron is absorbed from small intestine in bound form with β
globulin, apotransferrin.
Combination of apotransferrin with iron forms
transferrin.
•Transferrin binds with receptors in the membranes of the
intestinal epithelial cells.
•Transferrin is absorbed (by pinocytosis) into the epithelial
cells and later released into the blood capillaries in the form
of plasma transferrin.
Iron Absorption and Transport
Cont’d…
Slide 57
•Excess iron in the blood is deposited especially in the liver
hepatocytes.
In the cell cytoplasm, iron combines mainly with a
protein, apoferritin, to form ferritin.
•Smaller quantities of the iron in the storage pool are in an
extremely insoluble form called hemosiderin.
•Decrease in plasma iron causes, release of some of the iron in
storage pool in the form of transferrin in plasma to the area
of the where is needed.
Iron Storage
Cont’d…
•Excess iron in the blood is deposited especially in the liver
hepatocytes.
In the cell cytoplasm, iron combines mainly with a
protein, apoferritin, to form ferritin.
•Smaller quantities of the iron in the storage pool are in an
extremely insoluble form called hemosiderin.
•Decrease in plasma iron causes, release of some of the iron in
storage pool in the form of transferrin in plasma to the area
of the where is needed.
Iron Storage
Cont’d…
Slide 58
Cont’d…
Cont’d…
Slide 59
ABO Blood Types and Rh System
•Antigens are substances that can trigger a protective defense
mechanism called an immune response.
•Most antigens are proteins.
•Plasma membranes contain surface antigens (also called
agglutinogens) – substances that immune system recognizes
as “normal.”
Immune system ignores these substances rather than
attacking them as “foreign.”
ABO Blood Types and Rh System
•Antigens are substances that can trigger a protective defense
mechanism called an immune response.
•Most antigens are proteins.
•Plasma membranes contain surface antigens (also called
agglutinogens) – substances that immune system recognizes
as “normal.”
Immune system ignores these substances rather than
attacking them as “foreign.”
Slide 60
•Blood type is determined by the presence or absence of
specific surface antigens in RBC plasma membranes.
The surface antigens involved are integral membrane
glycoproteins or glycolipids.
Three surface antigens are of particular importance: A, B,
and Rh (or D).
•Based on the presence and absence of A and B agglutinogen,
there are four blood types:-
i.When agglutinogen A is present on RBCs, the blood is
type-A.
Cont’d…
•Blood type is determined by the presence or absence of
specific surface antigens in RBC plasma membranes.
The surface antigens involved are integral membrane
glycoproteins or glycolipids.
Three surface antigens are of particular importance: A, B,
and Rh (or D).
•Based on the presence and absence of A and B agglutinogen,
there are four blood types:-
i.When agglutinogen A is present on RBCs, the blood is
type-A.
Cont’d…
ii.When agglutinogen B is present on RBCs, the blood is
type-B.
iii.When both agglutinogen A & B exist together on RBCs,
the blood is type-AB.
iv.When neither agglutinogen A nor B are absent on RBCs,
the blood is type-O.
•The term Rh positive (Rh
+
) indicates the presence of the Rh
surface antigen, commonly called the Rh factor.
The absence of this antigen – Rh negative (Rh
–
).
Cont’d…
Slide 61
type-B.
iii.When both agglutinogen A & B exist together on RBCs,
the blood is type-AB.
iv.When neither agglutinogen A nor B are absent on RBCs,
the blood is type-O.
•The term Rh positive (Rh
+
) indicates the presence of the Rh
surface antigen, commonly called the Rh factor.
The absence of this antigen – Rh negative (Rh
–
).
Cont’d…
Slide 61
•Antibodies, also called agglutinins, are specialized molecules
produced by the immune system to attack foreign antigens.
The presence of anti-A and/or anti-B antibodies is
genetically determined.
•An individual with type A blood produces anti-B antibodies,
which attack type B antigens.
•An individual with type B blood produces anti-A antibodies,
which attack type A antigens.
•Type AB blood contains A and B antigens on the RBCs.
Cont’d…
Slide 62
produced by the immune system to attack foreign antigens.
The presence of anti-A and/or anti-B antibodies is
genetically determined.
•An individual with type A blood produces anti-B antibodies,
which attack type B antigens.
•An individual with type B blood produces anti-A antibodies,
which attack type A antigens.
•Type AB blood contains A and B antigens on the RBCs.
Cont’d…
Slide 62
They produce neither anti-A nor anti-B antibodies and
can receive a transfusion of any blood type.
Individuals with type AB blood – universal recipients.
•Type O blood have neither A nor B surface antigens, and
that person’s plasma contains both anti-A and anti-B
antibodies.
Individuals with type O blood – universal donors.
•The antibodies produced against a foreign blood type may
cause agglutination (clumping) or hemolysis (rupture) of the
donated erythrocytes.
Cont’d…
Slide 63
can receive a transfusion of any blood type.
Individuals with type AB blood – universal recipients.
•Type O blood have neither A nor B surface antigens, and
that person’s plasma contains both anti-A and anti-B
antibodies.
Individuals with type O blood – universal donors.
•The antibodies produced against a foreign blood type may
cause agglutination (clumping) or hemolysis (rupture) of the
donated erythrocytes.
Cont’d…
Slide 63
•Another type of cell surface antigen found on RBC is the Rh
factor.
Red blood cells that contain the Rh factor – Rh-positive.
RBCs without this factor – Rh-negative.
•This antigen also stimulates antibody production.
Rh-negative individuals that produce anti-Rh antibodies
should receive only Rh-negative blood.
•Rh-positive individuals that do not produce anti-Rh
antibodies can receive Rh-negative or Rh-positive blood.
Slide 64
Cont’d…
factor.
Red blood cells that contain the Rh factor – Rh-positive.
RBCs without this factor – Rh-negative.
•This antigen also stimulates antibody production.
Rh-negative individuals that produce anti-Rh antibodies
should receive only Rh-negative blood.
•Rh-positive individuals that do not produce anti-Rh
antibodies can receive Rh-negative or Rh-positive blood.
Slide 64
Cont’d…
Slide 65
Cross-Reactions in Transfusions
•When an antibody meets its specific surface antigen, the
RBCs agglutinate and may also hemolyze.
This reaction – cross-reaction or transfusion reactions.
•Clumps and fragments of RBCs under attack form drifting
masses that can plug small blood vessels in the kidneys,
lungs, heart, or brain, damaging affected tissues.
Can be prevented by ensuring that the blood types of the
donor and the recipient are compatible.
Cross-Reactions in Transfusions
•When an antibody meets its specific surface antigen, the
RBCs agglutinate and may also hemolyze.
This reaction – cross-reaction or transfusion reactions.
•Clumps and fragments of RBCs under attack form drifting
masses that can plug small blood vessels in the kidneys,
lungs, heart, or brain, damaging affected tissues.
Can be prevented by ensuring that the blood types of the
donor and the recipient are compatible.
Slide 66
•In practice, the surface antigens on the donor’s cells are more
important in determining compatibility than are the
antibodies in the donor’s plasma.
Unless large volumes of whole blood or plasma are
transferred, cross-reactions between the donor’s plasma
and the recipient’s blood cells will not produce
significant agglutination.
This is because the donated plasma is diluted quickly
through mixing with the large plasma volume of the
recipient.
Cont’d…
•In practice, the surface antigens on the donor’s cells are more
important in determining compatibility than are the
antibodies in the donor’s plasma.
Unless large volumes of whole blood or plasma are
transferred, cross-reactions between the donor’s plasma
and the recipient’s blood cells will not produce
significant agglutination.
This is because the donated plasma is diluted quickly
through mixing with the large plasma volume of the
recipient.
Cont’d…
One unit of whole blood, 500 mL, contains roughly 275
mL of plasma, only about 10% of normal plasma volume.
•When the goal is to increase the blood’s oxygen- carrying
capacity rather than its plasma volume, packed RBCs, with a
minimal amount of plasma, are often transfused.
This practice minimizes the risk of a cross-reaction.
Slide 67
Cont’d…
mL of plasma, only about 10% of normal plasma volume.
•When the goal is to increase the blood’s oxygen- carrying
capacity rather than its plasma volume, packed RBCs, with a
minimal amount of plasma, are often transfused.
This practice minimizes the risk of a cross-reaction.
Slide 67
Cont’d…
Slide 68
Slide 69
FORMATION OF BLOOD CELLS
•Hemopoiesis/hematopoiesis/ – the process by which the
formed elements of blood develop.
•Before birth, hemopoiesis first occurs in the yolk sac of an
embryo.
Later in the liver, spleen, thymus, and lymph nodes of a
fetus.
Red bone marrow becomes the primary site of
hemopoiesis in the last 3 months before birth, and
FORMATION OF BLOOD CELLS
•Hemopoiesis/hematopoiesis/ – the process by which the
formed elements of blood develop.
•Before birth, hemopoiesis first occurs in the yolk sac of an
embryo.
Later in the liver, spleen, thymus, and lymph nodes of a
fetus.
Red bone marrow becomes the primary site of
hemopoiesis in the last 3 months before birth, and
Slide 70
Continues as the source of blood cells after birth and
throughout life.
•Red bone marrow is a highly vascularized connective tissue
located in the microscopic spaces between trabeculae of
spongy bone tissue.
It is present chiefly in bones of the axial skeleton,
pectoral and pelvic girdles, and the proximal epiphyses
of the humerus and femur.
•In newborns, all bone marrow is red and thus active in
blood cell production.
Cont’d…
Continues as the source of blood cells after birth and
throughout life.
•Red bone marrow is a highly vascularized connective tissue
located in the microscopic spaces between trabeculae of
spongy bone tissue.
It is present chiefly in bones of the axial skeleton,
pectoral and pelvic girdles, and the proximal epiphyses
of the humerus and femur.
•In newborns, all bone marrow is red and thus active in
blood cell production.
Cont’d…
Slide 71
•In order to form blood cells, pluripotent stem cells in red
bone marrow produce two further types of stem cells.
These stem cells – myeloid stem and lymphoid stem cells.
•Myeloid stem cells begin their development in red bone
marrow and give rise to RBCs, platelets, monocytes,
neutrophils, eosinophils, and basophils.
•Lymphoid stem cells begin their development in red bone
marrow but complete it in lymphatic tissues.
They give rise to lymphocytes.
Cont’d…
•In order to form blood cells, pluripotent stem cells in red
bone marrow produce two further types of stem cells.
These stem cells – myeloid stem and lymphoid stem cells.
•Myeloid stem cells begin their development in red bone
marrow and give rise to RBCs, platelets, monocytes,
neutrophils, eosinophils, and basophils.
•Lymphoid stem cells begin their development in red bone
marrow but complete it in lymphatic tissues.
They give rise to lymphocytes.
Cont’d…
Slide 72
•During hemopoiesis, some of the myeloid stem cells
differentiate into progenitor cells.
Other myeloid stem cells and the lymphoid stem cells
develop directly into precursor cells.
•Progenitor cells are no longer capable of reproducing
themselves.
They are committed to giving rise to more specific
elements of blood.
•Some progenitor cells – colony-forming units (CFUs).
Cont’d…
•During hemopoiesis, some of the myeloid stem cells
differentiate into progenitor cells.
Other myeloid stem cells and the lymphoid stem cells
develop directly into precursor cells.
•Progenitor cells are no longer capable of reproducing
themselves.
They are committed to giving rise to more specific
elements of blood.
•Some progenitor cells – colony-forming units (CFUs).
Cont’d…
Slide 73
•CFU designation indicates the mature elements in blood that
they will produce.
CFU–E ultimately produces erythrocytes (red blood cells);
CFU–Meg produces megakaryocytes – source of platelets;
CFU–GM ultimately produces granulocytes (specifically,
neutrophils) and monocytes.
•Progenitor cells, like stem cells, resemble lymphocytes and
cannot be distinguished by their microscopic appearance
alone.
Cont’d…
•CFU designation indicates the mature elements in blood that
they will produce.
CFU–E ultimately produces erythrocytes (red blood cells);
CFU–Meg produces megakaryocytes – source of platelets;
CFU–GM ultimately produces granulocytes (specifically,
neutrophils) and monocytes.
•Progenitor cells, like stem cells, resemble lymphocytes and
cannot be distinguished by their microscopic appearance
alone.
Cont’d…
Slide 74
•In the next generation, the cells are called precursor cells,
also known as blasts.
•Over several cell divisions they develop into the actual
formed elements of blood.
Monoblasts develop into monocytes, eosinophilic
myeloblasts develop into eosinophils, and so on.
•Precursor cells have recognizable microscopic appearances.
•Several hormones called hemopoietic growth factors regulate
the differentiation and proliferation of particular cells.
Cont’d…
•In the next generation, the cells are called precursor cells,
also known as blasts.
•Over several cell divisions they develop into the actual
formed elements of blood.
Monoblasts develop into monocytes, eosinophilic
myeloblasts develop into eosinophils, and so on.
•Precursor cells have recognizable microscopic appearances.
•Several hormones called hemopoietic growth factors regulate
the differentiation and proliferation of particular cells.
Cont’d…
Slide 75
•Erythropoietin or EPO increases the number of red blood
cell precursors.
It is produced primarily by cells in the kidneys –
peritubular interstitial cells.
•Thrombopoietin or TPO is a hormone produced by the liver
that stimulates the formation of platelets.
•Cytokines are small glycoproteins that are typically
produced by red bone marrow cells, leukocytes,
macrophages, fibroblasts, and endothelial cells.
Cont’d…
•Erythropoietin or EPO increases the number of red blood
cell precursors.
It is produced primarily by cells in the kidneys –
peritubular interstitial cells.
•Thrombopoietin or TPO is a hormone produced by the liver
that stimulates the formation of platelets.
•Cytokines are small glycoproteins that are typically
produced by red bone marrow cells, leukocytes,
macrophages, fibroblasts, and endothelial cells.
Cont’d…
Slide 76
•Two important families of cytokines that stimulate white
blood cell formation are
Colony-stimulating factors (CSFs) and
Interleukins.
Cont’d…
•Two important families of cytokines that stimulate white
blood cell formation are
Colony-stimulating factors (CSFs) and
Interleukins.
Cont’d…
Slide 77
Slide 78
•Starts in the red bone marrow with a precursor cell –
proerythroblast.
•The proerythroblast divides several times, producing cells
that begin to synthesize hemoglobin.
•Ultimately, a cell near the end of the development sequence
ejects its nucleus and becomes a reticulocyte.
•Loss of the nucleus causes the center of the cell to indent,
producing the red blood cell’s distinctive biconcave shape.
Erythropoiesis
•Starts in the red bone marrow with a precursor cell –
proerythroblast.
•The proerythroblast divides several times, producing cells
that begin to synthesize hemoglobin.
•Ultimately, a cell near the end of the development sequence
ejects its nucleus and becomes a reticulocyte.
•Loss of the nucleus causes the center of the cell to indent,
producing the red blood cell’s distinctive biconcave shape.
Erythropoiesis
Slide 79
•Reticulocytes retain some mitochondria, ribosomes, and
endoplasmic reticulum.
•They pass from red bone marrow into the bloodstream by
squeezing between the endothelial cells of blood capillaries.
•Reticulocytes develop into mature red blood cells within 1 to
2 days after their release from red bone marrow.
Cont’d…
•Reticulocytes retain some mitochondria, ribosomes, and
endoplasmic reticulum.
•They pass from red bone marrow into the bloodstream by
squeezing between the endothelial cells of blood capillaries.
•Reticulocytes develop into mature red blood cells within 1 to
2 days after their release from red bone marrow.
Cont’d…
1.Proerythroblast.
2.Basophile erythroblast.
3.Polychromatophil erythroblast.
4.Ortochromatic erythroblast.
5.Reticulocytes
6.Erythrocytes.
Stages of Differentiation of RBC
Slide 80
2.Basophile erythroblast.
3.Polychromatophil erythroblast.
4.Ortochromatic erythroblast.
5.Reticulocytes
6.Erythrocytes.
Stages of Differentiation of RBC
Slide 80
Slide 81
•EPO is a glycoprotein hormone, stimulates the formation of
erythrocytes.
Normally, a small amount of EPO circulates in the blood
at all times.
•The kidneys play the major role in EPO production,
although the liver also produces some.
During the first weeks after birth, the liver, not the
kidneys, produces most EPO.
Hormonal Controls
Regulation of Erythropoiesis
•EPO is a glycoprotein hormone, stimulates the formation of
erythrocytes.
Normally, a small amount of EPO circulates in the blood
at all times.
•The kidneys play the major role in EPO production,
although the liver also produces some.
During the first weeks after birth, the liver, not the
kidneys, produces most EPO.
Hormonal Controls
Regulation of Erythropoiesis
Slide 82
•When certain kidney cells become hypoxic (oxygen deficient)
– accelerates the synthesis and release of EPO.
Because the liver is less sensitive than the kidneys to
hypoxia, newborns have a smaller EPO response to
anemia than do adults.
Because fetal hemoglobin (hemoglobin present at birth)
carries up to 30% more oxygen, the loss of fetal
hemoglobin, due to insufficient erythropoietin
production, makes the anemia worse.
Cont’d…
•When certain kidney cells become hypoxic (oxygen deficient)
– accelerates the synthesis and release of EPO.
Because the liver is less sensitive than the kidneys to
hypoxia, newborns have a smaller EPO response to
anemia than do adults.
Because fetal hemoglobin (hemoglobin present at birth)
carries up to 30% more oxygen, the loss of fetal
hemoglobin, due to insufficient erythropoietin
production, makes the anemia worse.
Cont’d…
Slide 83
•Note that it is not the number of erythrocytes in blood that
controls the rate of erythropoiesis.
Instead, control is based on their ability to transport
enough oxygen to meet tissue demands.
•Notice that hypoxia does not activate the BM directly.
Instead it stimulates the kidneys, which in turn provide
the hormonal stimulus that activates the bone marrow.
•The male sex hormone testosterone also enhances the
kidneys’ production of EPO.
Cont’d…
•Note that it is not the number of erythrocytes in blood that
controls the rate of erythropoiesis.
Instead, control is based on their ability to transport
enough oxygen to meet tissue demands.
•Notice that hypoxia does not activate the BM directly.
Instead it stimulates the kidneys, which in turn provide
the hormonal stimulus that activates the bone marrow.
•The male sex hormone testosterone also enhances the
kidneys’ production of EPO.
Cont’d…
Slide 84
•Also, a wide variety of chemicals released by leukocytes,
platelets, and even reticular cells stimulates bursts of RBC
production.
•Norepinephrine, epinephrine and prostaglandins stimulate
erythropoietin production.
•Is triggered by:
1. Less RBCs from bleeding …….low blood volume
2. Less RBCs due to excess RBC destruction ….. low Hb.
3. Low oxygen levels (high altitude, pulmonary disease)
4. Increased oxygen demand (exercise)
Cont’d…
•Also, a wide variety of chemicals released by leukocytes,
platelets, and even reticular cells stimulates bursts of RBC
production.
•Norepinephrine, epinephrine and prostaglandins stimulate
erythropoietin production.
•Is triggered by:
1. Less RBCs from bleeding …….low blood volume
2. Less RBCs due to excess RBC destruction ….. low Hb.
3. Low oxygen levels (high altitude, pulmonary disease)
4. Increased oxygen demand (exercise)
Cont’d…
Slide 85
Dietary Requirements
•The raw materials required for erythropoiesis include the
usual nutrients and structural materials — amino acids,
lipids, and carbohydrates.
•For the
final maturation of RBCs two important vitamins are
essentially required, Vitamin B
12
and folic acid.
•Vitamin B
12
(Cyanocobalamin) and folic acid
Essential for DNA synthesis.
Dietary Requirements
•The raw materials required for erythropoiesis include the
usual nutrients and structural materials — amino acids,
lipids, and carbohydrates.
•For the
final maturation of RBCs two important vitamins are
essentially required, Vitamin B
12
and folic acid.
•Vitamin B
12
(Cyanocobalamin) and folic acid
Essential for DNA synthesis.
Slide 86
Vitamin B
12 (Cyanocobalamin)
Obtained mostly from diet and absorbed from GIT.
Its absorption from intestine requires – intrinsic factor.
oCombines with vitamin B
12
in food and makes the B
12
available for absorption by the gut.
•Mechanism of Intrinsic factor to bind vitamin B
12
Intrinsic factor binds tightly with B
12
Intrinsic factor binds to specific receptor sites on mucosal
cells in the ileum.
Cont’d…
Vitamin B
12 (Cyanocobalamin)
Obtained mostly from diet and absorbed from GIT.
Its absorption from intestine requires – intrinsic factor.
oCombines with vitamin B
12
in food and makes the B
12
available for absorption by the gut.
•Mechanism of Intrinsic factor to bind vitamin B
12
Intrinsic factor binds tightly with B
12
Intrinsic factor binds to specific receptor sites on mucosal
cells in the ileum.
Cont’d…
Slide 87
Vitamin B
12
is transported in to blood by process of
pinocytosis
Stored in large quantities in the liver
•The minimum amount of vitamin B
12
required each day to
maintain normal red cell maturation is only 1 to 3μg.
Folic Acid (Pteroylglutamic Acid)
•Folic acid is also required for the synthesis of DNA and cell
maturation.
Cont’d…
Vitamin B
12
is transported in to blood by process of
pinocytosis
Stored in large quantities in the liver
•The minimum amount of vitamin B
12
required each day to
maintain normal red cell maturation is only 1 to 3μg.
Folic Acid (Pteroylglutamic Acid)
•Folic acid is also required for the synthesis of DNA and cell
maturation.
Cont’d…
Slide 88
•Folic acid is a normal constituent of green vegetables, some
fruits, and meats (especially liver).
•In the absence of folic acid, the synthesis of DNA decreases
causing failure of maturation.
•This leads to anemia in which the cells are larger and appear
in megaloblastic (proerythroblastic) stage.
Cont’d…
•Folic acid is a normal constituent of green vegetables, some
fruits, and meats (especially liver).
•In the absence of folic acid, the synthesis of DNA decreases
causing failure of maturation.
•This leads to anemia in which the cells are larger and appear
in megaloblastic (proerythroblastic) stage.
Cont’d…
•Have nuclei and other organelles but lacks hemoglobin.
•Function – defend the body against invasion by pathogens
and remove toxins, wastes, and abnormal or damaged cells.
•It types can be distinguished microscopically in a blood
smear by using either of Wright’s stain or Giemsa stain.
Traditionally, WBCs have been divided into two groups
based on their appearance after staining:
i.Granular leukocytes, or granulocytes (with abundant
stained granules) and
White Blood Cells (WBCs)
Slide 89
•Function – defend the body against invasion by pathogens
and remove toxins, wastes, and abnormal or damaged cells.
•It types can be distinguished microscopically in a blood
smear by using either of Wright’s stain or Giemsa stain.
Traditionally, WBCs have been divided into two groups
based on their appearance after staining:
i.Granular leukocytes, or granulocytes (with abundant
stained granules) and
White Blood Cells (WBCs)
Slide 89
ii.Agranular leukocytes, or agranulocytes (with few, if any,
stained granules).
•A typical microliter of blood contains 5000 to 10,000 WBCs.
Most of the WBCs in the body at any moment are in
connective tissue proper or
In organs of the lymphatic system.
•Circulating WBCs represent only a small fraction of the total
WBC population.
Slide 90
Cont’d…
stained granules).
•A typical microliter of blood contains 5000 to 10,000 WBCs.
Most of the WBCs in the body at any moment are in
connective tissue proper or
In organs of the lymphatic system.
•Circulating WBCs represent only a small fraction of the total
WBC population.
Slide 90
Cont’d…
91
•WBCs differ from RBCs in many aspects.
Larger in size.
Irregular in shape.
Nucleated.
Many types.
Granules are present in some type of WBCs.
Lifespan is shorter.
Cont’d…
•WBCs differ from RBCs in many aspects.
Larger in size.
Irregular in shape.
Nucleated.
Many types.
Granules are present in some type of WBCs.
Lifespan is shorter.
Cont’d…
•Circulating WBCs have four characteristics:
i.All Can Migrate Out of the Bloodstream.
When WBCs in the bloodstream are activated, they
contact and adhere to the vessel walls – margination.
After further interaction with ECs, the activated WBCs
squeeze between adjacent endothelial cells and enter the
surrounding tissue – emigration/diapedesis.
oIt is the process by which the leukocytes squeeze
through the narrow blood vessels.
WBC Circulation and Movement
Slide 92
i.All Can Migrate Out of the Bloodstream.
When WBCs in the bloodstream are activated, they
contact and adhere to the vessel walls – margination.
After further interaction with ECs, the activated WBCs
squeeze between adjacent endothelial cells and enter the
surrounding tissue – emigration/diapedesis.
oIt is the process by which the leukocytes squeeze
through the narrow blood vessels.
WBC Circulation and Movement
Slide 92
ii.All Are Capable of Amoeboid Movement.
It is a gliding motion made possible by the flow of
cytoplasm into slender cellular processes extended in the
direction of movement.
It involves the continuous rearrangement of bonds
between actin filaments, and it requires Ca
2+
and ATP.
This mobility allows WBCs to move through the
endothelial lining and into peripheral tissues.
Slide 93
Cont’d…
It is a gliding motion made possible by the flow of
cytoplasm into slender cellular processes extended in the
direction of movement.
It involves the continuous rearrangement of bonds
between actin filaments, and it requires Ca
2+
and ATP.
This mobility allows WBCs to move through the
endothelial lining and into peripheral tissues.
Slide 93
Cont’d…
iii.All Are Attracted to Specific Chemical Stimuli.
This characteristic, called positive chemotaxis, guides
WBCs to invading pathogens, damaged tissues, and other
active WBCs.
Chemotaxis is the attraction of WBCs towards the injured
tissues by the chemical substances released at the site of
injury.
•They include
Some of the bacterial or viral toxins,
Degenerative products of the inflamed tissues themselves
Slide 94
Cont’d…
This characteristic, called positive chemotaxis, guides
WBCs to invading pathogens, damaged tissues, and other
active WBCs.
Chemotaxis is the attraction of WBCs towards the injured
tissues by the chemical substances released at the site of
injury.
•They include
Some of the bacterial or viral toxins,
Degenerative products of the inflamed tissues themselves
Slide 94
Cont’d…
Slide 95
Cont’d…
Several reaction products of the “complement complex”
activated in inflamed tissues, and
Several reaction products caused by plasma clotting in
the inflamed area, as well as other substances.
•Chemotaxis is effective up to 100 μm away from an inflamed
tissue.
iv.Neutrophils, Eosinophils, and Monocytes Are Capable of
Phagocytosis.
Engulf pathogens, cell debris, or other materials.
Cont’d…
Several reaction products of the “complement complex”
activated in inflamed tissues, and
Several reaction products caused by plasma clotting in
the inflamed area, as well as other substances.
•Chemotaxis is effective up to 100 μm away from an inflamed
tissue.
iv.Neutrophils, Eosinophils, and Monocytes Are Capable of
Phagocytosis.
Engulf pathogens, cell debris, or other materials.
Slide 96
•Neutrophils and eosinophils are called microphages.
•Macrophages are monocytes that have active phagocytic.
•Whether phagocytosis will occur depends especially on three
selective procedures.
a)Most natural structures in the tissues have smooth
surfaces, which resist phagocytosis.
But if the surface is rough, the likelihood of
phagocytosis is increased.
Cont’d…
•Neutrophils and eosinophils are called microphages.
•Macrophages are monocytes that have active phagocytic.
•Whether phagocytosis will occur depends especially on three
selective procedures.
a)Most natural structures in the tissues have smooth
surfaces, which resist phagocytosis.
But if the surface is rough, the likelihood of
phagocytosis is increased.
Cont’d…
Slide 97
b)Most natural substances of the body have protective
protein coats that repel the phagocytes.
Conversely, most dead tissues and foreign particles
have no protective coats, which makes them subject to
phagocytosis.
c)The immune system of the body develops antibodies
against infectious agents such as bacteria.
The antibodies then adhere to the bacterial
membranes and thereby make the bacteria especially
susceptible to phagocytosis.
Cont’d…
b)Most natural substances of the body have protective
protein coats that repel the phagocytes.
Conversely, most dead tissues and foreign particles
have no protective coats, which makes them subject to
phagocytosis.
c)The immune system of the body develops antibodies
against infectious agents such as bacteria.
The antibodies then adhere to the bacterial
membranes and thereby make the bacteria especially
susceptible to phagocytosis.
Cont’d…
Slide 98
To do this, the antibody molecule also combines with
the C3 product of the complement cascade.
The C3 molecules, in turn, attach to receptors on the
phagocyte membrane, thus initiating phagocytosis.
This selection and phagocytosis process is called
opsonization.
Cont’d…
To do this, the antibody molecule also combines with
the C3 product of the complement cascade.
The C3 molecules, in turn, attach to receptors on the
phagocyte membrane, thus initiating phagocytosis.
This selection and phagocytosis process is called
opsonization.
Cont’d…
•Five types of leukocytes are classified as either granulocytes
or agranulocytes:
Granulocytes: neutrophils, eosinophils and basophils.
Agranulocytes: monocytes and lymphocytes.
•The granulocytes are phagocytic cells.
Their nuclei tend to be segmented into multiple lobes
and the cytoplasm of the cells contains numerous
granules.
Types of WBCs
Slide 99
or agranulocytes:
Granulocytes: neutrophils, eosinophils and basophils.
Agranulocytes: monocytes and lymphocytes.
•The granulocytes are phagocytic cells.
Their nuclei tend to be segmented into multiple lobes
and the cytoplasm of the cells contains numerous
granules.
Types of WBCs
Slide 99
•Agranulocytes contain no granules in their cytoplasm.
Have a single, large non-segmented nucleus.
•Neutrophils, eosinophils, basophils, and monocytes are part
of the body’s nonspecific defenses.
•Lymphocytes are responsible for specific defenses.
The mounting of a counterattack against specific types of
invading pathogens or foreign proteins.
Cont’d…
Slide 100
Have a single, large non-segmented nucleus.
•Neutrophils, eosinophils, basophils, and monocytes are part
of the body’s nonspecific defenses.
•Lymphocytes are responsible for specific defenses.
The mounting of a counterattack against specific types of
invading pathogens or foreign proteins.
Cont’d…
Slide 100
Neutrophils
•50 to 70 % of the circulating WBCs.
•Their granules are chemically neutral.
•Has a very dense, segmented nucleus with two to five lobes
resembling beads on a string – polymorphonuclear
leukocytes, or PMNs.
“Polymorphs,” or “polys,” as they are often called, are
roughly 12 μm in diameter.
•Their cytoplasm is packed with pale granules containing
lysosomal enzymes and bactericidal compounds.
Slide 101
•50 to 70 % of the circulating WBCs.
•Their granules are chemically neutral.
•Has a very dense, segmented nucleus with two to five lobes
resembling beads on a string – polymorphonuclear
leukocytes, or PMNs.
“Polymorphs,” or “polys,” as they are often called, are
roughly 12 μm in diameter.
•Their cytoplasm is packed with pale granules containing
lysosomal enzymes and bactericidal compounds.
Slide 101
•Neutrophils are highly mobile – first of the WBCs to arrive at
the site of an injury.
Specialized in attacking and digesting bacteria that have
been marked with antibodies or complement proteins.
•Upon encountering a bacterium, neutrophil quickly engulfs
it – their metabolic rate of the increases dramatically.
This respiratory burst accompanies the production of
highly reactive – hydrogen peroxide (H
2
O
2
) and superoxide
anions (O
2
-
), which can kill bacteria.
Slide 102
Cont’d…
the site of an injury.
Specialized in attacking and digesting bacteria that have
been marked with antibodies or complement proteins.
•Upon encountering a bacterium, neutrophil quickly engulfs
it – their metabolic rate of the increases dramatically.
This respiratory burst accompanies the production of
highly reactive – hydrogen peroxide (H
2
O
2
) and superoxide
anions (O
2
-
), which can kill bacteria.
Slide 102
Cont’d…
103
•The granules also contain antibody like peptides called
cathelicidins and defensins.
Antimicrobial peptides and are active against bacteria
and fungi.
•Membrane of neutrophils contains an enzyme called
NADPH oxidase.
It is activated by the toxic metabolites released from
infected tissues.
•The activated NADPH oxidase is responsible for bactericidal
action of neutrophils.
Cont’d…
•The granules also contain antibody like peptides called
cathelicidins and defensins.
Antimicrobial peptides and are active against bacteria
and fungi.
•Membrane of neutrophils contains an enzyme called
NADPH oxidase.
It is activated by the toxic metabolites released from
infected tissues.
•The activated NADPH oxidase is responsible for bactericidal
action of neutrophils.
Cont’d…
104
All these substances present in the granules and cell
membrane make the neutrophil a powerful and effective
killer machine.
•Neutrophils also secrete platelet-activating factor (PAF),
which is a cytokine.
It accelerates the aggregation of platelets during injury to
the blood vessel, resulting in prevention of excess loss of
blood.
•Generally, the primary function of neutrophils is to attack
and destroy invading bacteria.
Cont’d…
All these substances present in the granules and cell
membrane make the neutrophil a powerful and effective
killer machine.
•Neutrophils also secrete platelet-activating factor (PAF),
which is a cytokine.
It accelerates the aggregation of platelets during injury to
the blood vessel, resulting in prevention of excess loss of
blood.
•Generally, the primary function of neutrophils is to attack
and destroy invading bacteria.
Cont’d…
105
Mechanism of Action of Neutrophils
•Neutrophils are released in large number at the site of infection
from the blood.
•At the same time, new neutrophils are produced from the
progenitor cells.
•All the neutrophils move by diapedesis towards the site of
infection due to chemotaxis.
•Chemotaxis occurs due to the attraction by some chemical
substances called chemoattractants, which are released from the
infected area.
Cont’d…
Mechanism of Action of Neutrophils
•Neutrophils are released in large number at the site of infection
from the blood.
•At the same time, new neutrophils are produced from the
progenitor cells.
•All the neutrophils move by diapedesis towards the site of
infection due to chemotaxis.
•Chemotaxis occurs due to the attraction by some chemical
substances called chemoattractants, which are released from the
infected area.
Cont’d…
106
•After reaching the area, the neutrophils surround the area
and get adhered to the infected tissues.
•Chemoattractants increase the adhesive nature of
neutrophils so that all the neutrophils become sticky and get
attached firmly to the infected area.
•Each neutrophil can hold about 15 to 20 microorganisms at a
time.
•Now, the neutrophils start destroying the invaders.
•First, these cells engulf the bacteria and then destroy them
by means of phagocytosis.
Cont’d…
•After reaching the area, the neutrophils surround the area
and get adhered to the infected tissues.
•Chemoattractants increase the adhesive nature of
neutrophils so that all the neutrophils become sticky and get
attached firmly to the infected area.
•Each neutrophil can hold about 15 to 20 microorganisms at a
time.
•Now, the neutrophils start destroying the invaders.
•First, these cells engulf the bacteria and then destroy them
by means of phagocytosis.
Cont’d…
107
•Neutrophils are also involved in removal of tissue debris
and therefore play a role in the healing process.
Neutrophils eliminate bacteria and tissue debris by way
of phagocytosis.
As a result, these materials are internalized within a cell
membrane-bound vesicle.
In this way, the phagocytized material is degraded by
these enzymes without any damage to the rest of the cell.
Cont’d…
•Neutrophils are also involved in removal of tissue debris
and therefore play a role in the healing process.
Neutrophils eliminate bacteria and tissue debris by way
of phagocytosis.
As a result, these materials are internalized within a cell
membrane-bound vesicle.
In this way, the phagocytized material is degraded by
these enzymes without any damage to the rest of the cell.
Cont’d…
•Most neutrophils have a short life span, surviving in the
bloodstream for only about 10 hours.
When actively engulfing debris or pathogens, they may
last 30 minutes or less.
•A neutrophil dies after engulfing one to two dozen bacteria.
But its breakdown releases chemicals that attract other
neutrophils to the site.
•A mixture of dead neutrophils, cellular debris, and other
waste products form the pus.
Slide 108
Cont’d…
bloodstream for only about 10 hours.
When actively engulfing debris or pathogens, they may
last 30 minutes or less.
•A neutrophil dies after engulfing one to two dozen bacteria.
But its breakdown releases chemicals that attract other
neutrophils to the site.
•A mixture of dead neutrophils, cellular debris, and other
waste products form the pus.
Slide 108
Cont’d…
Eosinophils
•Named – their granules stain darkly with eosin, a red dye.
•Has typically bilobed (two-lobed) nucleus.
•Represent 2 – 4 % of the circulating WBCs and are similar in
size to neutrophils.
•Eosinophils attack objects that are coated with antibodies.
They will engulf antibody-marked bacteria, protozoa, or
cellular debris.
Slide 109
•Named – their granules stain darkly with eosin, a red dye.
•Has typically bilobed (two-lobed) nucleus.
•Represent 2 – 4 % of the circulating WBCs and are similar in
size to neutrophils.
•Eosinophils attack objects that are coated with antibodies.
They will engulf antibody-marked bacteria, protozoa, or
cellular debris.
Slide 109
•Eosinophils are responsible for detoxification, disintegration
and removal of foreign proteins.
Their primary mode of attack is the exocytosis of toxic
compounds – nitric oxide and cytotoxic enzymes.
•The number of circulating eosinophils increases
dramatically during a parasitic infection.
Are particularly effective against multicellular parasites
that are too big to engulf.
•They are sensitive to circulating allergens – their increase in
number during allergic reactions as well.
Slide 110
Cont’d…
and removal of foreign proteins.
Their primary mode of attack is the exocytosis of toxic
compounds – nitric oxide and cytotoxic enzymes.
•The number of circulating eosinophils increases
dramatically during a parasitic infection.
Are particularly effective against multicellular parasites
that are too big to engulf.
•They are sensitive to circulating allergens – their increase in
number during allergic reactions as well.
Slide 110
Cont’d…
•Eosinophils are also attracted to sites of injury.
Where they release enzymes that reduce inflammation
produced by mast cells and neutrophils.
This will control the spread of inflammation to adjacent
tissues.
Slide 111
Cont’d…
Where they release enzymes that reduce inflammation
produced by mast cells and neutrophils.
This will control the spread of inflammation to adjacent
tissues.
Slide 111
Cont’d…
112
Mechanism of Action of Eosinophils
•Eosinophils are neither markedly motile nor phagocytic like
the neutrophils.
•Some of the parasites are larger in size.
•Still eosinophils attack them by some special type of cytotoxic
substances present in their granules.
•When released over the invading parasites from the granules,
these substances become lethal and destroy the parasites.
Mechanism of Action of Eosinophils
•Eosinophils are neither markedly motile nor phagocytic like
the neutrophils.
•Some of the parasites are larger in size.
•Still eosinophils attack them by some special type of cytotoxic
substances present in their granules.
•When released over the invading parasites from the granules,
these substances become lethal and destroy the parasites.
113
•The lethal substances present in the granules of eosinophils
and released at the time of exposure to parasites or foreign
proteins are:
i.Eosinophil peroxidase:
This enzyme is capable of destroying helminths
(parasitic worms), bacteria and tumor cells.
ii.Major basic protein (MBP):
It is very active against helminths.
•The lethal substances present in the granules of eosinophils
and released at the time of exposure to parasites or foreign
proteins are:
i.Eosinophil peroxidase:
This enzyme is capable of destroying helminths
(parasitic worms), bacteria and tumor cells.
ii.Major basic protein (MBP):
It is very active against helminths.
114
It destroys the parasitic worms by causing distension
(ballooning) and detachment of the tegumental sheath
(skin-like covering) of these organisms.
iii.Eosinophil cationic protein (ECP):
This substance is the major destroyer of helminths
and it is about 10 times more toxic than MBP.
It destroys the parasites by means of complete
disintegration.
It is also a neurotoxin.
It destroys the parasitic worms by causing distension
(ballooning) and detachment of the tegumental sheath
(skin-like covering) of these organisms.
iii.Eosinophil cationic protein (ECP):
This substance is the major destroyer of helminths
and it is about 10 times more toxic than MBP.
It destroys the parasites by means of complete
disintegration.
It is also a neurotoxin.
Basophils
•Named – granules that stain darkly with basic dyes.
In a standard blood smear – deep purple or blue.
•Measuring 8–10 µm in diameter, basophils are smaller than
neutrophils or eosinophils.
•Are also relatively rare, accounting for less than 1%.
•Their granules contain histamine and heparin.
Slide 115
•Named – granules that stain darkly with basic dyes.
In a standard blood smear – deep purple or blue.
•Measuring 8–10 µm in diameter, basophils are smaller than
neutrophils or eosinophils.
•Are also relatively rare, accounting for less than 1%.
•Their granules contain histamine and heparin.
Slide 115
•The same compounds are released by mast cells in damaged
connective tissues.
But mast cells and basophils are distinct populations
with separate origins.
•The mast cells and basophils release histamine, as well as
smaller quantities of bradykinin and serotonin.
Indeed, it is mainly the mast cells in inflamed tissues that
release these substances during inflammation.
•The immunoglobulin E (IgE) – causes allergic reactions.
Slide 116
Cont’d…
connective tissues.
But mast cells and basophils are distinct populations
with separate origins.
•The mast cells and basophils release histamine, as well as
smaller quantities of bradykinin and serotonin.
Indeed, it is mainly the mast cells in inflamed tissues that
release these substances during inflammation.
•The immunoglobulin E (IgE) – causes allergic reactions.
Slide 116
Cont’d…
Slide 117
•Basophils and mast cells play an important role in allergic
reactions.
This is because of the presence of receptors for IgE in
mast cells and basophil membrane.
Then, when the specific antigen for the specific IgE
antibody subsequently reacts with the antibody.
The resulting attachment of antigen to antibody causes
the mast cell or basophil to rupture.
Cont’d…
•Basophils and mast cells play an important role in allergic
reactions.
This is because of the presence of receptors for IgE in
mast cells and basophil membrane.
Then, when the specific antigen for the specific IgE
antibody subsequently reacts with the antibody.
The resulting attachment of antigen to antibody causes
the mast cell or basophil to rupture.
Cont’d…
Slide 118
And release exceedingly large quantities of histamine,
bradykinin, serotonin, heparin, slow-reacting substance
of anaphylaxis, and a number of lysosomal enzymes.
Other chemicals released by stimulated basophils attract
eosinophils and other basophils to the area.
•Functions of basophils are executed by the release of some
important substances from their granules such as:
Heparin: essential to prevent the intravascular blood
clotting.
Cont’d…
And release exceedingly large quantities of histamine,
bradykinin, serotonin, heparin, slow-reacting substance
of anaphylaxis, and a number of lysosomal enzymes.
Other chemicals released by stimulated basophils attract
eosinophils and other basophils to the area.
•Functions of basophils are executed by the release of some
important substances from their granules such as:
Heparin: essential to prevent the intravascular blood
clotting.
Cont’d…
119
Histamine, slow-reacting substances of anaphylaxis,
bradykinin and serotonin: produce the acute
hypersensitivity reactions by causing vascular and tissue
responses.
Proteases and myeloperoxidase: destroy the
microorganisms.
Cytokine: Cytokine such as interleukin-4 accelerates
inflammatory responses and kill the invading organisms.
Basophils cont’d…
Histamine, slow-reacting substances of anaphylaxis,
bradykinin and serotonin: produce the acute
hypersensitivity reactions by causing vascular and tissue
responses.
Proteases and myeloperoxidase: destroy the
microorganisms.
Cytokine: Cytokine such as interleukin-4 accelerates
inflammatory responses and kill the invading organisms.
Basophils cont’d…
•Are spherical cells that may exceed 15 µm in diameter.
•Due to size – monocytes are fairly easy to identify.
•Their nucleus is large and tends to be oval or kidney bean–
shaped rather than lobed.
•Account for 2 – 8% of circulating WBCs.
•Remaining in circulation for only about 24 hours before they
enter into peripheral tissues and become tissue macrophage.
Monocytes
Slide 120
•Due to size – monocytes are fairly easy to identify.
•Their nucleus is large and tends to be oval or kidney bean–
shaped rather than lobed.
•Account for 2 – 8% of circulating WBCs.
•Remaining in circulation for only about 24 hours before they
enter into peripheral tissues and become tissue macrophage.
Monocytes
Slide 120
•Macrophages are aggressive phagocytes, often attempting to
engulf items as large as or larger than themselves.
They also release chemicals that attract and stimulate
neutrophils, monocytes, and other phagocytic cells.
Also secrete substances that draw fibroblasts into the
region.
oThe fibroblasts then begin producing scar tissue,
which will wall off the injured area.
Slide 121
Cont’d…
engulf items as large as or larger than themselves.
They also release chemicals that attract and stimulate
neutrophils, monocytes, and other phagocytic cells.
Also secrete substances that draw fibroblasts into the
region.
oThe fibroblasts then begin producing scar tissue,
which will wall off the injured area.
Slide 121
Cont’d…
Slide 122
•Another large portion of monocytes becomes attached to the
tissues and remains attached for months or even years until
they are called on to perform specific local protective
functions.
They have the same capabilities as the mobile
macrophages to phagocytize large quantities of bacteria,
viruses, necrotic tissue, or other foreign particles in the
tissue.
•And, when appropriately stimulated, they can break away
from their attachments and once again become mobile
macrophages that respond to chemotaxis and all the other
stimuli related to the inflammatory process.
Cont’d…
•Another large portion of monocytes becomes attached to the
tissues and remains attached for months or even years until
they are called on to perform specific local protective
functions.
They have the same capabilities as the mobile
macrophages to phagocytize large quantities of bacteria,
viruses, necrotic tissue, or other foreign particles in the
tissue.
•And, when appropriately stimulated, they can break away
from their attachments and once again become mobile
macrophages that respond to chemotaxis and all the other
stimuli related to the inflammatory process.
Cont’d…
Slide 123
•Thus, the body has a widespread “monocyte-macrophage
system” in virtually all tissue areas.
The total combination of monocytes, mobile
macrophages, fixed tissue macrophages, and a few
specialized endothelial cells in the bone marrow, spleen,
and lymph nodes is called the reticuloendothelial system.
However, all or almost all these cells originate from
monocytic stem cells; therefore, the reticuloendothelial
system is almost synonymous with the monocyte-
macrophage system.
Cont’d…
•Thus, the body has a widespread “monocyte-macrophage
system” in virtually all tissue areas.
The total combination of monocytes, mobile
macrophages, fixed tissue macrophages, and a few
specialized endothelial cells in the bone marrow, spleen,
and lymph nodes is called the reticuloendothelial system.
However, all or almost all these cells originate from
monocytic stem cells; therefore, the reticuloendothelial
system is almost synonymous with the monocyte-
macrophage system.
Cont’d…
Slide 124
•Tissue macrophage is a first line of defense against infection.
Within minutes after inflammation begins, the
macrophages already present in the tissues.
When activated by the products of infection and
inflammation, the first effect is rapid enlargement of each
of these cells.
Next, many of the previously sessile macrophages break
loose from their attachments and become mobile,
forming the first line of defense against infection during
the first hour or so.
Cont’d…
•Tissue macrophage is a first line of defense against infection.
Within minutes after inflammation begins, the
macrophages already present in the tissues.
When activated by the products of infection and
inflammation, the first effect is rapid enlargement of each
of these cells.
Next, many of the previously sessile macrophages break
loose from their attachments and become mobile,
forming the first line of defense against infection during
the first hour or so.
Cont’d…
Slide 125
•Within the first hour or so after inflammation begins, large
numbers of neutrophils begin to invade the inflamed area.
•This is caused by products from the inflamed tissues that
initiate the following reactions:
1)They alter the inside surface of the capillary
endothelium, causing neutrophils to stick to the capillary
walls in the inflamed area.
Cont’d…
•Within the first hour or so after inflammation begins, large
numbers of neutrophils begin to invade the inflamed area.
•This is caused by products from the inflamed tissues that
initiate the following reactions:
1)They alter the inside surface of the capillary
endothelium, causing neutrophils to stick to the capillary
walls in the inflamed area.
Cont’d…
Slide 126
This effect is called margination.
2)They cause the intercellular attachments between the
endothelial cells of the capillaries and small venules to
loosen, allowing openings large enough for neutrophils
to pass by diapedesis.
3)Other products of inflammation then cause chemotaxis of
the neutrophils toward the injured tissues.
•Because the blood neutrophils are already mature cells, they
are ready to immediately begin their scavenger functions for
killing bacteria and removing foreign matter.
Cont’d…
This effect is called margination.
2)They cause the intercellular attachments between the
endothelial cells of the capillaries and small venules to
loosen, allowing openings large enough for neutrophils
to pass by diapedesis.
3)Other products of inflammation then cause chemotaxis of
the neutrophils toward the injured tissues.
•Because the blood neutrophils are already mature cells, they
are ready to immediately begin their scavenger functions for
killing bacteria and removing foreign matter.
Cont’d…
Lymphocytes
•Are slightly larger than RBCs.
•Have a large, round nucleus surrounded by a thin halo of
cytoplasm.
•Account for 20 – 30% of the circulating WBC population.
•Lymphocytes continuously migrate from the bloodstream,
through peripheral tissues, and back to the bloodstream.
Circulating ones represent only a small fraction.
Slide 127
•Are slightly larger than RBCs.
•Have a large, round nucleus surrounded by a thin halo of
cytoplasm.
•Account for 20 – 30% of the circulating WBC population.
•Lymphocytes continuously migrate from the bloodstream,
through peripheral tissues, and back to the bloodstream.
Circulating ones represent only a small fraction.
Slide 127
Most of them are in other connective tissues and in
organs of the lymphatic system.
•The circulating blood contains three functional classes of
lymphocytes.
1.T cells are responsible for cell-mediated immunity.
A specific defense mechanism against invading foreign
cells, and for the coordination of the immune response.
T cells either enter peripheral tissues and attack foreign
cells directly, or they control the activities of other
lymphocytes.
Slide 128
Cont’d…
organs of the lymphatic system.
•The circulating blood contains three functional classes of
lymphocytes.
1.T cells are responsible for cell-mediated immunity.
A specific defense mechanism against invading foreign
cells, and for the coordination of the immune response.
T cells either enter peripheral tissues and attack foreign
cells directly, or they control the activities of other
lymphocytes.
Slide 128
Cont’d…
2.B cells are responsible for humoral immunity.
A specific defense mechanism that involves the
production of antibodies.
oThese antibodies are distributed by blood, lymph, and
interstitial fluid.
oAntibodies – capable of attacking foreign antigens
throughout the body.
Activated B cells differentiate into plasma cells, which
are specialized to synthesize and secrete antibodies.
Slide 129
Cont’d…
A specific defense mechanism that involves the
production of antibodies.
oThese antibodies are distributed by blood, lymph, and
interstitial fluid.
oAntibodies – capable of attacking foreign antigens
throughout the body.
Activated B cells differentiate into plasma cells, which
are specialized to synthesize and secrete antibodies.
Slide 129
Cont’d…
•The T cells responsible for cellular immunity must migrate
to their targets.
But antibodies produced by plasma cells in one location
can destroy antigens almost anywhere in the body.
3.Natural killer (NK) cells – responsible for immune
surveillance – detection and subsequent destruction of
abnormal cells.
NK cells, also known as large granular lymphocytes, are
important in preventing cancer.
Slide 130
Cont’d…
to their targets.
But antibodies produced by plasma cells in one location
can destroy antigens almost anywhere in the body.
3.Natural killer (NK) cells – responsible for immune
surveillance – detection and subsequent destruction of
abnormal cells.
NK cells, also known as large granular lymphocytes, are
important in preventing cancer.
Slide 130
Cont’d…
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