MEDF1012A (2022-2023)

The Biology of Blood Cells

Francis Lam
School of Biomedical Sciences
email: [email protected]

24th March 2023 (Fri), 9:30-11:15

Lee Shau Kee Building (LSK), LT6
Identify the major blood components and their functions

Understand ABO and Rhesus (Rh) blood typing

Describe the pathophysiology of haemolytic disease of the

new born

Describe the three major components of haemostasis

Describe the mechanisms of the fibrinolytic system and

natural anticoagulants

Understand the roles of blood components in the innate and

adaptive immunity

2
General Functions Regulation:
of Blood (1) Blood transfers heat to the skin surface to be lost
(2) Blood buffers blood pH at about 7.4, and
maintains osmotic composition
Prevention of blood
loss:
Blood elements form a clot Defence:
to reduce blood lost Blood elements defend against
(haemostasis). microbes entering body openings or
wounds

Hydraulic Force:
Blood’s hydraulic force (blood
pressure) sustains urine formation
by kidneys
Transport:
Blood transport gases (e.g. O2),
nutrients, waste products, and
chemical messages between
organs, tissues, and cells.
3
 Composition of Blood
• Two major components of blood:
 Fluid (Plasma)
 Solid matters (Formed
elements)

4
Plasma Function Source
Water Maintains blood volume; transports Absorbed from
(90-92% of plasma) molecules intestine
Plasma Proteins Maintain blood osmotic pressure and pH Liver
(7-8% of plasma)
Albumins Maintain blood volume and pH
Globulins Transport: fight infection
Fibrinogens Coagulation
Salts Maintain blood osmotic pressure and pH; Absorbed from
(less than 1% of plasma) aid metabolism intestine
Gases Lungs Tissues
Oxygen Cellular respiration
Carbon dioxide End product of metabolism
Nutrients Food for cells Absorbed from
Lipids intestine
Glucose
Amino acids
Nitrogenous wastes Excretion by kidneys Liver
uric acid
urea
Other
Hormones, vitamins, etc. Aid metabolism Varied
5
 Formed elements (I) - Buffy Coat
• Constitutes <1% of whole blood; it contains

Leukocytes

Platelets

https://cdn4.vectorstock.com/i/1000x1000/74/33/leukocytes-vector-10497433.jpg
6
 Formed elements (II)
- Haematocrit (packed cell volume)
Erythrocyte (red blood cell) volume
Haematocrit =
Total blood volume
= 0.45 (45%)

• Constitute ~45% of whole blood

• The most dense component of blood

• Red blood cells (RBCs) are the most prevalent

cells in blood (~6,000,000 per l blood)

 transport O2 from the lungs to tissues and

CO2 from tissues to the lungs
7
Haematopoiesis is the formation of blood cellular components

Red bone marrows are active, whereas, yellow bone marrow

are inactive

From http://en.wikipedia.org/wiki/File:Hematopoesis_EN.svg 8
 多能造血幹細胞 Leukocytes (white blood cells; WBCs)
白細胞 (白血球)

( ) = Amount present in white blood cells

存在於白血細胞數量

骨髓祖 淋巴祖

原始粒 
巨核細胞 小淋巴 細胞

紅血球 肥大細胞
 B淋巴 
自然殺傷細胞
（大顆粒淋巴細胞） 細胞

T淋巴
細胞
單核細胞
嗜鹼性粒 嗜酸性粒細 Total = (25 to 38%)
中性粒 (3 to 7%)
細胞 細胞 胞
(<1%) (54 to 62%) (1 to 3%)
漿細胞
(Platelets)
血小板

巨噬細胞
http://upload.wikimedia.org/wikipedia/commons/f/f0/Hematopoiesis_simple.svg
9
Identify the major blood components and their functions

Understand ABO and Rhesus (Rh) blood typing

Describe the pathophysiology of haemolytic disease of the

new born

Describe the three major components of haemostasis

Describe the mechanisms of the fibrinolytic system and

natural anticoagulants

Understand the roles of blood components in the innate and

adaptive immunity

10
 Blood group is determined by antigens called agglutinogens
on red blood cells

The most well known blood group system is the ABO blood
group

 determined by the absence or presence of two antigens

on red blood cells; A antigen and B antigen

A antigen B antigen A antigen Neither A or

B antigen

B antigen

Blood Group A Blood Group B Blood Group AB Blood Group O

11
Antigens determine Antibodies determine blood Transfusion reaction
blood group group that cannot be received (antibody-antigen reaction that
causes haemolysis of donor
RBCs)

Anti-B antibodies can bind to

B antigens on RBCs of blood
group B donor

Anti-A antibodies can bind to

A antigens on RBCs of blood
group A donor

Has no antibody and so will

not affect donor blood of any
blood group

Anti-A and anti-B antibodies

can bind to A and B antigens
on RBCs of donors of different
blood groups
12
 Blood Transfusion Reaction
Antibodies can bind to specific antigens on RBCs to cause
agglutination and destruction (haemolysis) of cells

It can be prevented by cross matching of blood before blood

transfusion

(type B)

13
 Donor is blood
B
group _____.
Host is blood
A
group _____.

Transfusion reaction
From:
http://www.pc.maricopa.edu/Biology/rcotter/BIO%20205/LessonBuilders/
Chapter%2016LB/Ch16LessonBuilder_print.html

Transfused blood are haemolysed and cannot carry oxygen

Clumped RBCs clog small blood vessels throughout the body

Haemoglobin from haemolysed RBCs passes into kidney to

cause cell death and renal shutdown, and recipient may die
14
First studied from the blood of Rhesus monkey

Consists of 50 defined blood-group antigens

The commonly-used terms Rh factor, Rh positive and Rh

negative refer to the D antigen only

 Rh+ ( has D antigen , common)

 Rh- ( no D antigen )

15
 Transfusion reaction
The Rhesus (Rh) Blood Groups Antibody-antigen
reaction that causes
haemolysis of donor
RBCs

Has no anti-Rh D
antibody and so will not
affect donor blood of
Rh+ or Rh- blood group

On second exposure,
anti-Rh D antibodies
can bind to D antigens
on RBCs of Rh+ blood
donor

Rh- subject should not receive Rh+ blood

 exposure to the foreign Rh D antigens
causes anti-Rh D antibodies in the
Rh- subject

From: http://www.nobelprize.org/educational/medicine/landsteiner/readmore.html 16
 Development of haemolytic disease of the
foetus and newborn (HDFN; HDN)

Rh- mother with Rh+ baby:

1st birth: Rh+ RBCs leak into maternal circulation during delivery

Mother produces anti-Rh Ab (anti-D antibodies)

Subsequent birth with second Rh+ baby

Anti-Rh Ab cross the placenta into foetal circulation

Anti-Rh Ab attack the foetal RBCs, causing haemolysis

17
First pregnancy Second pregnancy

18
 Preventive measure on HDFN

Rh- mothers pregnant with a Rh+ infant are given Rh immune

globulin (RhIG) at 28 and 34 weeks during pregnancy, and
within 72 hours after delivery

Injection with RhIG soon after birth so that it

Rh antigen on
binds to any foetal red cells with the D
foetal blood
antigen before the mother is able to produce
cells in maternal
an immune response and form anti-D IgG
circulation
From Fig. 15.3 Principles of Hematology P. J. Haem P. 168

19
Identify the major blood components and their functions

Understand ABO and Rhesus (Rh) blood typing

Describe the pathophysiology of haemolytic disease of the

new born

Describe the three major components of haemostasis

Describe the mechanisms of the fibrinolytic system and

natural anticoagulants

Understand the roles of blood components in the innate and

adaptive immunity

20
Haemostasis is the instinctive response for the body to prevent
or stop bleeding (haemorrhage)

Significant blood loss is associated with low oxygen transport

capacity (due to reduced RBCs) and low blood flow and pressure
(due to reduced blood volume)

There are 3 components in haemostasis

 (1) vasoconstriction

 (2) platelet plug formation

 (3) coagulation

21
1 Vasoconstriction Vessel lumen’s original size
Contracted smooth muscle

• When a blood vessel is broken,

it triggers vascular spasm by release of vasoconstrictors from:

 damaged endothelial cells, e.g. endothelin

 platelets, e.g. 5-hydroxytryptamine (5-HT; serotonin)

 pain reflex activation of autonomic nerves, e.g. noradrenaline

(NA; norepinephrine)

• Vasoconstriction limits but does not stop blood loss from the
ruptured vessel

 it is instantaneous but short-lived; nevertheless, it buys precious

time for platelets and coagulation to effect a lasting solution
22
 2 Platelet plug formation Normal blood vessel

• Platelet adherence to undamaged

blood vessels is normally prevented by
prostacyclin (prostaglandin I2, PGI2)
and nitric oxide (NO) released from the
endothelium
Damaged blood vessel
• In damaged blood vessels, platelets
will adhere to the exposed collagen Platelet
activation

fibres of the subendothelial vessel wall;

the first of the 3 processes for platelet
plug formation…

23
i Platelet adhesion - Platelets adhere to the exposed
collagen fibres via interaction of its glycoprotein 1b (GP1b)
receptors with von Willebrand factor (vWF) synthesized by
endothelium

ii
i

Blood
vessel wall

Modified from: C. VanPutte, J. Regan, & A. Russo.

Seely’s Anatomy & Physiology, 9th ed., 2011 Platelet plug Smooth muscle cell

ii Platelet activation - Activation is initiated by collagen

fibres, adenosine diphosphate (ADP), and thrombin; causes
platelets to synthesize thromboxane A2 (TXA2) and to release
contents of their dense granules, which contain ADP and 5-HT 24
iii Platelet aggregation - The released mediators cause
platelets to change from a discoid shape to a sphere with spiny
projections (pseudopods), which increase the chance of
making contact with other platelets

iii
ii
i

Blood
vessel wall

Platelet plug Smooth muscle cell

Platelets aggregate, or clump together, using fibrinogen and

vWF as connecting agents via their glycoprotein IIb/IIIa
(gpIIb/IIIa) receptors
25
ADP and TXA2 cause further platelet activation and act as
chemotactic factors to attract more platelets

iii
ii
i

Blood
vessel wall

Platelet plug Smooth muscle cell

This positive feedback loop forms the platelet plug, which

temporarily seals the break in the vessel wall

26
3 Coagulation (blood clot)

• Reinforces platelet plug with fibrin threads

• Blood transformed from liquid to gel by a series of reactions

using clotting factors (procoagulants); nos. 1 to XIII

 Vitamin K needed to synthesize 4 of clotting factors

Fibrinogen is converted into fibrin, which forms

a clot with platelets and RBCs to stop bleeding.
From Fig.10.10 Human Form/Human Function P.394

27
28
The blood clotting (coagulation) cascade

• Intrinsic pathway

 triggered by negatively charged surfaces

(activated platelets, collagen, glass)

 uses factors present within blood

• Extrinsic pathway

 triggered by exposure to tissue factor (TF),

i.e. factor III

 bypasses several steps of intrinsic pathway,

so faster

• Once prothrombin activator formed, clot forms

in 10–15 sec
29
Identify the major blood components and their functions

Understand ABO and Rhesus (Rh) blood typing

Describe the pathophysiology of haemolytic disease of the

new born

Describe the three major components of haemostasis

Describe the mechanisms of the fibrinolytic system and

natural anticoagulants

Understand the roles of blood components in the innate and

adaptive immunity

30
• Limit blood clot to avoid intravascular coagulation

• Macrophages in blood and tissues help to remove

activated clotting factors

• Coagulation automatically initiates fibrinolysis

• Plasma coagulation inhibitors

 natural anti-coagulants

 anti-coagulant drugs

31
The fibrinolytic (thrombolytic) system
Removes unneeded clots after healing

Begins within two days; continues for several

Plasminogen activators convert plasminogen to plasmin;

a fibrin-digesting enzyme

Factor XI Thrombin Streptokinase (from bacteria)

Factor XII Tissue plasminogen activator (tPA)

Plasminogen Plasmin

Fibrin Soluble fibrin fragments

32
 Natural anti-coagulants

1 Protein C & protein S

• Thrombin binds to
thrombomodulin on the
surface of endothelial cells
and activates protein C

• Activated protein C (APC)

together with protein S (cofactor)
can digest factors Va and VIIIa
From http://206.47.151.137/bcdecker/figures/acp/1002_fig5.gif

33
2 Antithrombin III (AT-III)

• Circulating protease that blocks the activity of thrombin

(factor II) and some other clotting factors

• Facilitated by heparin, a substance present in plasma

and on the surface of endothelial cells

Heparin binds to ATIII

to increase its actions

Modified from http://journals.prous.com/journals/dof/20022705/html/df270446/images/deligoparin_f2.gif

34
3 Tissue factor pathway inhibitors (TFPI)

• Secreted by endothelial cells and 3

binds to tissue factor/ factor VIIa
complexes

• Inhibits the ability to generate

factor Xa, and the subsequent
generation of thrombin
2
1

Modified from http://www.nature.com/bmt/journal/v41/n8/images/1705990f2.jpg 35

Identify the major blood components and their functions

Understand ABO and Rhesus (Rh) blood typing

Describe the pathophysiology of haemolytic disease of the

new born

Describe the three major components of haemostasis

Describe the mechanisms of the fibrinolytic system and

natural anticoagulants

Understand the roles of blood components in the innate and

adaptive immunity

36
• The ability of an organism to resist the development of a disease
by the entry of foreign organisms is called immunity.

Microorganisms Bacteria Fungi Protozoa Viruses

細菌 真菌 原生動物 病毒

Example of tuberculosis candidiasis malaria Covid-19

diseases 結核病 念珠菌症 瘧疾 新冠肺炎

• Functional system rather than organ system

37
 Innate defence system Adaptive defence system
(non-specific) (specific, acquired)

Surface barriers Internal defences Cell-mediated Antibody-mediated

(humoral)

In born; always present and Slow responses (days)

available
Provide a more powerful defence
Rapid responses (min); than the innate response
activated immediately following
Highly specific for the invading
infection or injury
pathogen
No memory
Provide “immunological memory”
38
 Innate defence system (non-adaptive)

Surface barriers Internal defence

(1st line defence) (2nd line defence)
Necessary when microorganisms
Skin, mucous membranes,
invade deeper tissues
chemicals
 Phagocytes
 Natural killer cells
 Cytokines
 Complement proteins
 Inflammation
https://image.slidesharecdn.com/chapter21theimmunesystem1innateimmunity-150223173052-
conversion-gate01/95/chapter-21-the-immune-system-1-8-638.jpg?cb=1424712977

39
White blood cells (WBCs)

WBCs and the cells derived from

them are the most important cellular
components of the immune system

To be effective, WBCs must move

into tissues where they are needed

 chemotactic factors are parts of microbes or chemicals

released by tissue cells that act as chemical signals to attract
WBCs
 important chemotactic factors include complement proteins,
leukotrienes, kinins, and histamine
40
Examples of blood cells and their primary functions in immunity

Cells Primary Function

Monocyte Leaves the blood and enters tissues to become macrophage
that can phagocytize pathogens and cellular debris.

Neutrophil Phagocytosis and inflammation; usually the first cell to leave the
blood and enter infected tissues.

Basophil Motile cell that leaves the blood, enter tissues, and releases
heparin and histamine, which can promote inflammation.

Eosinophil Phagocytize antigen-antibody complexes and allergens.

Releases an array of cytotoxic granule cationic proteins that are
capable of inducing tissue damage and dysfunction.

Natural killer Nonphagocytic large granular lymphocyte. Kills virus-infected or

cell cancerous cells before the adaptive immune system occurs.

Lymphocytes Responsible for adaptive (specific) immunity

41
 Phagocytes
Phagocytes include many types of WBCs, e.g. macrophages,
neutrophils, monocytes, mast cells, and dendritic cells

1. Phagocytes adheres to pathogens or debris.

2. Phagocyte forms pseudopods that eventually

engulf the particles, forming a phagosome.

3. Lysosome fuses with the phagocytic vesicle,

forming a phagolysome.

4. Lysosomal enzymes digest the particles,

leaving a residual body.

5. Exocytosis of the vesicle removes indigestible

and residual material.
42
 Recruitment of phagocytes at site of injury
(3) Mast cells secrete factors that mediate (2) Platelets from blood (1) Bacteria and other
vasodilation. Increase delivery of blood, release blood-clotting pathogens enter wound.
plasma, and cells to injured area. proteins at wound site.

(4) Neutrophils secrete

factors that kill and (5) Neutrophils
degrade pathogens. and macrophages
remove pathogens
by phagocytosis.
(7) Inflammatory response
continues until the foreign
material is eliminated and (6) Macrophages secrete
the wound is repaired. cytokines that attract immune
cells and activate cells
involved in tissue repair.
http://infoaboutorgantransplants.weebly.com/uploads/2/3/1/2/23127080/1752340_orig.jpg
43
Macrophages and other sentinel cells such as dendritic cells
are present in tissues such as skin
 they have Toll-like receptors (TLRs) that recognize
pathogen-associated molecular patterns (PAMPs)
that are expressed specifically by microbes

Once microbes have breached

physical barriers, their PAMPs
are recognised by TLRs of
sentinel cells, which activate
immune cell responses such
as release of cytokines

44
 Self
Natural Killer cells

• Recognise abnormal cells by a lack

of “self” cell-surface receptors, i.e.
major histocompatibility complex
class 1 (MHC-1) molecules Missing
self
• When in contact with cells that have
no MHC-1 or cells with non-self or
abnormal MHC-1 molecules, the
natural killer cell will release its
granular contents (perforin and
α-defensins) to destroy the foreign Non-self
cell

• Kill virus-infected or cancerous cells

45
 Cytokines

Produced by a broad range of cells, including immune cells like

macrophages, B lymphocytes, T lymphocytes and mast cells, as
well as endothelial cells, fibroblasts, and various stromal cells
(connective tissue cells of an organ)

Cytokines include chemokines, interferons (IFN), interleukins

(IL), and tumour necrosis factors (TNF)

Cytokines utilize both autocrine and paracrine mechanisms to

regulate the action and expression of cells of the inflammatory
and immune systems

46
 Complement proteins

Complement factors (Complement; C) comprise of ~30 blood

proteins that could enhance both innate and adaptive defences

Activated by lectins binding to specific

sugars on microorganism’s surface

Activated spontaneously.
Lack of inhibitors on
microorganism’s surface
Activated by antibodies
allows process to proceed
coating target cell
2

1
(MAC) formed from activated
complement components (C5b,
C6-C9) that insert into the target
membrane, creating pores that
3 can lyse the target cell

47
 Inflammation

Prevents injurious agents from spreading to adjacent tissues

Disposes pathogens and dead tissue cells by releasing

inflammatory chemicals

Promotes tissue repair;

release chemotaxins that attract
phagocytes (and other immune
cells) to the area

Alerts adaptive immune system

Heat Redness Swelling Pain Loss of function

48
 Tissue Injury

Release of inflammatory chemicals

(e.g. histamine, complements, prostaglandins, kinins, etc.)

Increased capillary permeability

Arterioles dilate Activation of
sensory neurones Capillaries leak fluid
Local hyperaemia (exudate formation)
(increase blood flow
to area) Leaked protein-rich fluid in
tissue spaces

Compression of
Hot Redness Pain sensory neurones Swelling

Severe pain and structural damage

Loss of function
49
 Innate defence system Adaptive defence system
(non-specific) (specific, acquired)

Induction phase Effector phase

Th1 Th2
Cell-mediated Antibody-mediated
component (Humoral) component

Th1, Th2 = T helper 1 and 2 lymphocytes

50
 多能造血幹細胞 Leukocytes (white blood cells; WBCs)
白細胞 (白血球)

( ) = Amount present in white blood cells

存在於白血細胞數量

骨髓祖 淋巴祖

原始粒 
巨核細胞 小淋巴 細胞

紅血球 肥大細胞
 B淋巴 
自然殺傷細胞
（大顆粒淋巴細胞） 細胞

T淋巴
細胞
單核細胞
嗜鹼性粒 嗜酸性粒細 Total = (25 to 38%)
中性粒 (3 to 7%)
細胞 細胞 胞
(<1%) (54 to 62%) (1 to 3%)
漿細胞
(Platelets)
血小板 Lymphocytes are the key
cells in adaptive immunity
巨噬細胞
http://upload.wikimedia.org/wikipedia/commons/f/f0/Hematopoiesis_simple.svg
51
 Cell-mediated immune response

CD8+ T cells give rise to cytotoxic T cells that can destroy

virus-infected cells by programming them to undergo apoptosis
(programmed cell death)

CD4+ Th1 cells can release cytokines to recruit and activate

macrophages
 macrophages can kill intracellular pathogens by generating
and secrete cytokines and many other inflammatory mediators

Note:
CD8 and CD4 are protein markers on T cells
CD (cluster of differentiation) is a transmembrane glycoprotein that serves as
a co-receptor for the T cell receptor (TCR)
52
 Antibody-mediated (humoral) response

Five main classes of antibody – IgG, IgM, IgE, IgA, and IgD

The side arms (Fab portion) of

the Y shape antibody are the
recognition sites for specific
Fab
antigens (i.e. foreign proteins
or polysaccharides to the host)
Fc

The stem (Fc portion) activates

host defences
53
Functions of antibodies

54
 Lymphocyte induction and effector mechanisms
Induction phase Effector phase
Antigen presentation Clonal expansion and maturation
Antibodies
P
Antigen Th2 B P
P
MB Antibody-mediated immunity
IL-4
TGF-,
IL-10 Treg
Restrain immune response
IL-2 IL-2
Th0
T TGF-,
Th0 Th0 IL-6, IL-21
CD4 Th0 Th17
Cell-mediated immunity
Th17 Th17
Th17
MHC II IL-2
Th17
Th17
Th17
MHC I
Th1 Th17Th17
Th1 Th1 Th1 Activation of
Th1 macrophages
T MT Th1 Th1
CD8
Th1
IL-2 Th1 Th1
Tc
Tc
Tc Tc Kill virally infected cells
Antigen-presenting cell e.g. dendritic cell

MHC = major histocompatibility complex molecules; T = naïve T cells (CD8+ or CD4+); Tc = cytotoxic T cells; Th = T helper cells;
Treg = T regulatory cells; MB / T = memory B / T cells; TGF- = transforming growth factor-; IL = interleukin; P = plasma cells
Modified from Rang et al. (2012). Rang & Dale’s Pharmacology, 7th ed., Churchill Livingstone, Elsevier 55
 Secondary immune response to antigen A is faster
and larger because antibodies and memory B cells that
recognise antigen A are present; enable rapid cloning of
Primary immune response to
plasma cells to secrete antibodies against antigen A.
antigen A occurs after a delay
Primary immune response to antigen B is similar to the
primary immune response to antigen A.

Vaccination;
first exposure = killed
microbe or its protein

56
 Identify the major blood components and their functions

Understand ABO and Rhesus (Rh) blood typing

Describe the pathophysiology of haemolytic disease of the new born

Describe the three major components of haemostasis

Describe the mechanisms of the fibrinolytic system and natural

anticoagulants

Understand the roles of blood components in the innate and adaptive immunity

Read:
(1)“Human Anatomy & Physiology” (11th edition) by E.N. Marieb & K.H.
Hoehn (2019), Chapter 17, Publisher: Pearson.
(2) “Human Physiology” by Cheryl Watson (2015), Chapter 4, P.71-86,
Publisher: Jones & Barlett Learning.

Attempt an online Quiz on Blackboard.

Answer will be released on Monday (27 March) afternoon
57