BIO10003

The Immune System

Reference Text:
Janeway’s Immunobiology, 8th Edition
Biology, 8th Edition, Campbell, Reece and Meyers,
Biochemistry. Andrew.
 Popular phrase

"Next to sanitation and clean drinking water,

vaccines have been called the greatest public
health intervention in history”
 John Snow, water pump, cholera,
chlorination of tap water & epidemiology
 John Snow, water pump, cholera,
chlorination of tap water & epidemiology
 Diseases from toilet

Lab Office Toilet

“River toilet”
 The world is dirty!!

• We are constantly surrounded by

organisms that can cause disease:
> Parasites (worms, Plasmodium, etc.)
> Bacteria (E. coli, Vibrio cholerae, etc)
> Viruses (influenza virus, etc.)

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For info

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For info

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For info

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For info

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 Why aren’t we sick?

• With all of these microbes around us,

why aren’t we sick?
• Do we need to be vaccinated for ALL
of them?

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 We have a good immune system

Immunology is the
Anatomical

study of the body’s

Physiological

defense against
infection.

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Our immune system

Anatomical
Physiological

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Our immune system

Respiratory system - lung carries out the

function

Circulatory system - heart & blood vessels

provides the main functions

Digestive system – stomach & intestines

provides the main functions

Immune system – which organs provide

the main functions?

It is not the organs but the cells that

provide the main functions.

e.g. macrophage (a phagocyte) can be

found in almost all organs

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 Immunology
• Its origin linked to Edward Jenner

• Jenner observed that milkmaids infected with cowpox

would “immune” to smallpox

• He unethical injected a young boy in 1796 with weaken

cowpox to see if immune against smallpox

• His experiments lead to the idea of vaccination (vaccinus

means “from cows”)

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Conduct an totally unethical experiment …
The Innate Immune System
 Innate immunity

• Is the first line of defense

• Mechanisms not specific to a
particular pathogen.
• Fast: activated within minutes after
Anatomical
infection Physiological

• These mechanisms can be broadly

separated into two parts:
• Barrier defense: anatomical and
physiological

• Internal defenses: phagocytic cells,

antimicrobial proteins, inflammatory
response, natural killer cells, etc.
Anatomical
Physiological
If there wasn't any injury,
microbes would be prevented
from entering our skin

Skin – example of anatomical

barrier

Lysozyme in sweat – example

of physiological barrier

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 How barriers work?

(=Anatomical)

(=Physiological)

Urine in urinary tract – physiological

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• Hair

• Sebum (“natural
wax”)

• Physiological
barrier,
antimicrobial…

• No need to wash
hair!
 Barrier
1. Anatomic barriers:
- The skin & mucous membranes.

2. Physiological barriers:
• include temperature, low pH & chemical mediators
• these factors make the host environment hostile for
pathogens

Anatomical & physiological barriers cannot be altered & are not

responsible for the induction of adaptive immune response

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 Anatomical barrier

• Skin:
> Probably the main barrier
> Our skin is about 2 square meters

• Mucous Membranes:
> Line our digestive, respiratory & reproductive
Herpes
tracts
> About 400 square meters
> Much of it is lined with cilia, covered with mucus
or acids

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 The secretions from skin is a
physiological barrier
• Secretions (e.g. sweat, tears, urine, mucus) prevent entry or kill pathogens:
> Acid in gastric juice
> Spermine & zinc in semen
> Lactoperoxidase in milk
> Lysozyme in tears, nasal secretions & saliva
> Antimicrobial peptides, e.g. psoriasin kills E. coli

• Normal flora which compete for pathogens for food or secrete inhibitory
substances, thus preventing the growth of the pathogen

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 Antimicrobial peptides/proteins
Examples:
Chemokines
- protein messengers that stimulate migration & activation of cells)
Cytokines (-, -, -interferons)
– antiviral, activate macrophage

C-reactive proteins in the complement system – lyse bacteria

Psoriasin (S100A7)

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No need to wash hands after toilet visit?

• Psoriasin is secreted by epithelial cells of

the skin against Escherichia coli by
disrupting their cell membranes.

• This is the reason that in countries with poor

sanitation, human skin is exposed to E.coli
strains from faecal matter but it does not
usually result in an infection.

https://en.wikipedia.org/wiki/S100A7
 Antimicrobial peptides e.g. complement proteins

https://www.youtube.com/watch?v=OubAhPYGDsc
 Membrane attack complex
(=complement dependent cytotoxicity)
 C reactive proteins

Bacterial surface They regulate:

Complement
dependent
cytotoxicity (CDC)

Antigen antibody complex initiate

classical pathway

All three pathways come to formation

of C3 convertase, an active enzyme

The other fragments, C3b binds to

bacteria for opsonization. While
fragment C3a & C5a are important for

  inflammation.

 But it is C3b that triggers C5b, C6, C7,
Also known as CDC C8 and finally C9 to form membrane
attach complex
Barrier defenses:
• Anatomical
• Physiological Anatomical
Physiological

Internal defenses:
• Phagocytic cells
• Antimicrobial proteins
• Inflammation
• NK cells
 What is inflammation?

Anatomical
Physiological

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 How if microbe enter the skin due to puncture wound?

Your wound swollen – fluid enters the tissue

Swollen + heat + painful – This is inflammation

Phagocytosis by
neutrophil & macrophage

+ histamine

Neutrophil

Pus, a fluid rich in white blood cells, dead microbes, and cell debris, accumulates at the site of
inflammation
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 Phagocytosis & inflammation

Phagocytosis & inflammation CAN

INDUCE adaptive immune response i.e.
the production of antibodies.

• The major functions of phagocytosis & inflammation:

• Identify pathogen
• Kill pathogens by phagocytosis (internalization of
pathogen)
• Release cytokines to signal immune cells to migrate to
infection site (trigger inflammation)
• Pathogen digested, but some antigens are preserved &
display on cell surface for recognition by T cells. This is
how inflammation ACTIVATE adaptive immune system.

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 Phagocytic cells
• Macrophages – located mainly in tissue, waiting
for pathogens, presenting antigen.
• Dendritic cells – better than macrophage in
displaying pathogen's antigen on cell surface
(therefore the most important “antigen
presenting cells”)
• Neutrophils – located mainly in blood, can
migrate out to the tissue (When?)
• Eosinophils – like neutrophil, but triggered by
parasites instead of microbes.
• Basophils – phagocyte, but similar to mast cell
that they can release chemical signals.
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 Phagocytosis
Phagocytosis is the internalization
of pathogens/particles by cells

Ingested particles is contained in a

vesicle (called phagosome)

Phagosome fuses with lysosome to

form a phagolysosome

Lysosomal enzymes released →

killing & degradation of
pathogens/particles

And presenting some of these

particles for T cell recognition (thus
linking to adaptive immunity)
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Macrophage

• Large mononuclear phagocytic cell

• Important functions of the macrophage:

> Scavenger cell – phagocytizes microbes, debris etc.
> Release cytokines, trigger inflammation
> Antigen presenting cell
• Are called monocytes in blood. Monocytes are not active
• Once migrate to tissue, become active macrophages, & stay
mainly in the tissues

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Dendritic cell
• Found in lymphoid tissues & most other tissues
• At certain development stage, grows branches or “dendrites”
• The most important antigen presenting cells

• There are two main functional subsets:

> Plasmacytoid – produce interferons
> Conventional – stimulate T cell response

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Neutrophil
• Also known as polymorphonuclear neutrophilic
leukocytes – has multi-lobed nucleus

• They are a major class of white blood cell in

blood.

• Neutrophilic granules – do not take up stains.

• Remember inflammation! They enter infected

tissues & engulfing the pathogens!

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Eosinophil
• They are a bit different from neutrophil:
• Granules stained bright pink by eosine dye
• In blood too, but number is low.
• Number increased (called eosinophilia) due to:
• Parasitic infections – worms, fleas, etc.(vs. neutrophil increased
due to microbes!)
• Allergic / Atopy - tendency for some people to produce
immediate hypersensitivity reactions against harmless
substances

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Basophil
Also found in blood like neutrophil, BUT:
• Granules stained bluish by basic dyes
• Number extremely low (lower than eosinophil)
• Function unknown, probably function similar to mast cells and also perform
phagocytosis.

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 Inflammatory Response
Can be local or systemic (throughout the body)

Systemic – usually has fever due to pyrogens.

Pyrogens could be some things released by
macrophages, and/or the toxins from pathogens

Systemic inflammation can be overwhelming –

remember fluid escape from blood > septic
shock > death
Mast Cells
• Large
• Found in tissues, most abundantly
in submucosal tissues & dermis
• Functions:
• Detect pathogen into the skin,
• Phagocytosis
• Release histamine & other
chemical signals

• PROBLEM: Also trigger by certain

antigen, causing allergic reactions
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Mast Cells
• Mast cell bind IgE (it has Fc
receptor),
• And IgE binds antigen.
• This cause degranulation,
histamine will be released
White blood cells differentiation
Phagocytes and lymphocytes
Lymphoid lineage:
cytotoxicity
• B cells, T cells
and NK cells
• Not performing
phagocytosis

Granulocyte lineage
• Performing
phagocytosis
 Natural killer (NK) cells
• Large, granular NK immunosurvellance
• Non-T, non-B lymphocytes

Three main functions:

1. Immunosurveillance:
• Cells in our body must have
protein called MHC on the
surface
• Abnormal cells (virus-infected,
tumors) don't have MHC, thus
recognized by NK cells through
receptors
• Kill via cytotoxicity - granules
containing granzymes & perforin
2. Early response against viral
infection
3. ADCC (need antibody)
 Pathogen destroyed by Infected cells Pathogen destroyed by
interferons produced destroyed via antibodies & cytotoxic T
2. NK cells are an early component of by macrophages, cytotoxicity cells (under adaptive
host response against virus infection dendritic cells, etc. immunity)

• When the body infected by a

NEW virus, NK cells reacts first
to CONTAIN the virus by
cytotoxicity & releasing
interferon gamma),

• This gives time for adaptive

immunity i.e. T cells and B cells
to be generated.

• Persons without NK cells are

susceptible to early phase of
viral infection i.e. herpes virus
infection
 ADCC – NK cell has Fc receptors …
The person already has The “tail” of antibody is Binding trigger release of Pathogen dies (apoptosis).
antibodies. Antibodies Fc. NK cells have granules containing
bind to the pathogen. receptors for Fc. granzyme & perforin.

Pathogen

NK can also react following mediation by antibodies, a process

known as Antibody dependent cell mediated cytotoxicity (ADCC)
For general knowledge only!

C
How could a white blood cell know the
presence of pathogen?
 PAMPs and PRRs
PAMP: pathogen-associated molecular patterns
PRR: Pattern recognizing receptor

White blood cell

 Das ist ja toll!
That is great!

Toll gene identified in Drosophila in 1985 by Christiane

Nüsslein-Volhard.

The gene in question, when mutated, makes the

Drosophila flies look unusual due to inhibition in larval
development.

The researchers were so surprised that they

spontaneously shouted out in German "Das ist ja toll!"
which translates as "That's great!".

Besides development, Toll has effects in immune system

as well.

Mammals have similar proteins like Toll, so they are

called toll-like receptors.
Macrophage has PRR that recognize PAMPs on
the pathogen surface

Pattern Recognition Receptors (PRR)

PAMP PRR
---------------------------------------------------
Lipopolysaccharide (LPS) TLR4
Lipopeptide TLR2
Flagellin TLR5
CpG island (mutation) TLR9
ssRNA (viruses) TLR7
dsRNA (viruses) TLR3

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 Many pathogen has PAMPS on their surface
These can be recognized by pattern recognition receptors

Very important PRRs are Toll like receptors (TLRs)

Characteristics of PAMPs:
1. Expressed by a many pathogens (e.g.
LPS by bacteria)
2. Essential for the survival of the
pathogen (e.g. dsRNA for certain
viruses)
3. Hosts (like us) has no PAMPs (so killing
pathogens will not kill us) – e.g.
flagellin, CpG DNA sequence, …
 Antigen presenting cells link between innate &
adaptive immunity
Antigen presentation cells (APC) i.e. dendritic cell
engulfs pathogen & breaks it into antigens (which are
peptide fragments) & display them on MHC molecules
on the cell surface.
(These APCs would normally not perform phagocytosis
immediately, even though they are phagocytes)

Because T cells can only recognize antigen that

presented on MHC.
(Otherwise our immune cells will attack all sorts of small
molecules like protein, carbohydrate, penicillin, etc., but
these allergic reactions do happened in some people)

Recognition will then trigger adaptive immunity

 Antigen Presenting Cells

Major functions of antigen-presenting cells (APCs):

1. Process antigens.

2. Display their peptide fragments on the cell surface.

3. Display other co-stimulatory proteins required for activating T cells.

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Dendritic cell,
Macrophage,
Neutrophil

Require MHCII, co-stimulation to

stimulate helper T cell through TCR
(TCR: T cell receptor) Phagocytosis ?
Dendritic cell,
Macrophage,
Neutrophil

Require MHCII, co-stimulation to

stimulate helper T cell through TCR
(TCR: T cell receptor)
 Innate Immunity
Summary
• Innate immunity
> present before exposure to pathogens (no need prior exposure)
> effective from the time of birth (always available to combat wide range of
pathogens)
• It involves non-specific responses (the response is not specific to any individual
pathogens)

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 Adaptive Immunity
Introduction
• Acquired immunity (= adaptive immunity):
> develops after exposure to pathogens, toxins or foreign substances.

• It involves a very specific response to pathogens.

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 Know how to link…

Can anyone explain what happened?

Next lecture notes

THE ADAPTIVE IMMUNE SYSTEM
Also known as Acquired Immunity
 Picking nose – Good or bad ?
2018 – bad !
 Shaking hands is definitely bad,
immunologically speaking

Louis Pasteur did not shake

hands with anyone at all because
he was afraid he would catch
diseases
 AQUIRED IMMUNITY

• Description:
> Also known as ADAPTIVE IMMUNITY
> Both vertebrates & invertebrates have innate
immunity
> But, only vertebrates have acquired immunity
> Innate immunity is a generalized response to
a broad range of pathogens
> Acquired immunity involves lymphocytes (B
and T cells) that recognize specific pathogens
& elicit responses specific to each pathogen
 AQUIRED IMMUNITY

Acquired immunity = Humoral immune + cell-mediated immune (CMI)

responses

Humoral – is mediated by B lymphocytes (= B cells)

CMI – is mediated by T lymphocytes (= T cells)

AQUIRED IMMUNITY
 AQUIRED IMMUNITY

• T cells - matured in the thymus (Where

is thymus?)

• B cells - matured in bone marrow

Thymus & bone marrow are central

immune organs

The others i.e. lymph nodes, spleen,

are peripheral immune organs
75
 Cell with receptors that could not
bind to an antigen:
• will be destroyed by
apoptosis.
Cell with receptors that are self-
reactivity (bind to our own
molecules):
• apoptosis, or anergy
(nonfunctional).

http://people.eku.edu/ritchisong
/301notes4b.html
 The adaptive immune response

• How each individual B and T cells can be specialised to recognise

specific antigen (or epitope of foreign molecule)?
• Answer – they have specific antigen receptors
• One lymphocyte has one type of receptor to recognise one epitope
(= antigenic determinant)
• One lymphocyte can have 100,000 receptors, all the same type !
• Antigen receptor for B-cell – membrane bound antibody
• Antigen receptor for T-cell - T cell receptor (TCR)
• B cells give rise to plasma cells, which
secrete proteins called antibodies or
immunoglobulins
Clonal expansion & selection
Two types of “clones” are produced
• Effector cells – short-lived
• Memory cells – long lived

Effector cells:
• Effector B cells (plasma cells)

• Effector T cells (CTL)

 The adaptive immune response

• The acquired immune system has the following important

properties:
> Not reactive against host cells - attack only the antigen
but not self
> Immunological memory - can remember previous
infection
 Why are so many types of antibodies, each
against a single pathogen?

DNA

TRUE
NOT TRUE

mRNA

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The segment of genes randomly combined >

random mutation > diverse population of
antibodies
 The adaptive immune response

• Memory cells (both B and T)

were created during the first
exposure.

• Memory cells cause hasten

secondary immune
response to the same
pathogen.
THE HUMORAL IMMUNE RESPONSE
 The humoral immune response

• Humoral immunity is immunity due to antibodies

• Humoral immunity can be transferred by the transfer of

serum containing specific antibodies (passive
immunisation)
 B cells
• Produce antibody

• Develop in the bone marrow from progenitor

cells, they have a membrane bound antibody (B
cell receptor = BCR)

• Each B cell produce a single antibody because

their genes already mutated and undergone
random rearrangements.
• B cells are produced in bone marrow but
circulating to various parts of body, including
lymph nodes
• While at secondary lymphoid organ (i.e. lymph
nodes), B cells are exposed to antigens & helper
T cells (Th)
• If a single B cell has “receptor” that can bind the
antigen, it will be activated by Th to become
plasma cells that secrete antibodies
Key points:
• Antigen recognition by B cell
• Receptor mediated endocytosis
• Antigen presentation on MHCII to
Helper T cell
• Activation into plasma cells and
more memory cells
 Antibodies

• All antibodies have same basic structure Fab

• Antibody is immunoglobulins, a protein
• Structure has:
• One constant (C) region
• Two variable (V) region, (variable because its
amino acid sequence varies from one B cell to
another due to gene rearrangement) – enable
binding specifically to a particular antigen Fc
 Antibodies

Antigen can have more than one epitopes.

In this example, the antigen has two epitope.

One epitope bind to one antibody

The other bind to another antibody.

Both bindings are specific.

 How antibodies combat pathogen?
The 4 Mechanisms

1. Neutralization:
> Antibody bind to pathogens, prevent their
binding to cellular receptors, thus
preventing entry of the pathogen into
cells to cause infection

2. Opsonisation:
> facilitates the phagocytosis of pathogen
by neutrophils and macrophages
 How antibodies combat pathogen?
The 4 Mechanisms
3. Complement dependent cytotoxicity (CDC).
• Pathogens bound by Ab can activate the classical pathway of
complement system, causing membrane attach complex.
Remember the complement system?

4. Antibody-dependent cell-mediated cytotoxicity (ADCC)

• Infected host cells express antigens on their surface
• Antibody's “heads” (Fab) bind to antigens on pathogen
• Antibody's tail (Fc) can bind to Fc receptor of NK cell
• This activate NK cells to release toxins to killthe infected cells
 How antibodies combat
pathogen?
or virus Killed via CDC Killed via ADCC

The 4 Mechanisms
 Antibodies

• Isotype or class of an antibody determines its specific

“effector mechanism”
• 5 isotypes/classes:
• IgG, IgM, IgA, IgE & IgD
94
Also important
in inflammation

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Summary
Summary
Summary
Summary
Summary
CELL MEDIATED IMMUNITY
 The adaptive immune response

Specific & tightly fit (high affinity) Not that specific, not that fit (lower affinity)
 The cellular immune response

• T cells play the main role

• T cells cannot be transferred to another person –

therefore unlike antibody, which can be transferred
(passive immunisation)
 The cellular immune response

• Two types of T cells:

> T Helper Cells (= CD4 T cell, or Th cell)
> Cytotoxic T Cells (= CD8 T cell, or cytotoxic T lymphocyte, CTL)
 The cellular immune response

• The CD4+ and CD8+ T cells are different in

functions because they bind to different Major
Histocompatibility complex (MHC) molecules:
> CD4+ (or Helper T cells) – bind to MHC II 4, H, II (more angles!)

> CD8+ (or cytotoxic T cells) – bind to MHC I 8, C, I (more rounded!)

HELPER
T LYMPHOCYTES
Helper T cells “help” many other
immune cells!

107
Helper T cells “help” many other
immune cells!

108
Helper T cells “help” many other
immune cells!

“Help” = activate
(use the most
correct term)

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 Helper T cells (TH cell)

• T Helper cells stimulate or “help”:

• B cells to multiply & make antibody (clonal
expansion)
• Cytotoxic T cell to multiply (clonal expansion)
Can skew immune response either 100% antibody or 100% cytotoxic

T cell, or mixed

• Has TCR (T cell receptor) that can bind antigen

• TCR only bind to peptide fragment (=epitopes) in

complex with MHC class II on the surface of APCs 110

 Helper T cells

• Based on different cytokine

secretion patterns, TH cell
groups into two types:
> TH1 cells – secrete mainly
IL2 >> macrophages

> TH2 cells – secrete mainly

Neutralizing
IL4 >> antibodies antibody
 SUMMARY

• TH1 cells: • TH2 cells:

> Activate macrophages to > Initiate B-cell responses by
destroy microbes (e.g. activating naïve B cells to
mycobacteria) that already proliferate & secrete IgM
engulfed.
> And further drive B cells to
> Activate B cells to produce
differentiate & produce
strongly opsonizing IgG
IgG for neutralization
subclasses
> Produce mainly IL-4
> Produce IFN-γ, IL-2
Neutralizing
antibody
 CYTOTOXIC
T LYMPHOCYTES
T cell releases cytotoxins
(perforin and granzymes)
 CYTOTOXIC T LYMPHOCYTES

• For killing intracellular pathogens i.e. viruses & mycobacteria

• TCRs recognize antigen bound to MHC I.
• Once activated, CTL undergo expansion leading to more CTLs & memory T cells
• Cytolytic: toxin released from CTL upon binding to antigen-MHC I complex, causing apoptosis
(cell death)
 CYTOTOXIC T LYMPHOCYTES
• Pathogen's peptide that induce CTL are call “CTL epitopes”
• CTL important for intracellular – bacteria or virus hiding inside cells, or tumour cells
• CTL epitope must bind to MHCI
• Each individual has different MHC (=HLA). The reason for organ transplant
rejection.
• Diversity of MHC is due to polygenic (control by several genes) and polymorphism
(many alleles for each gene)
 Acquired level:
PROFILE:
Name T Helper cell (TH).
HELPful but bossy.
See ANTIGEN cases presented by APC
B cell
“I want to be APC too once in a while”
Innate level:

for unusual crimes, need in inform superior (T helper cell) for his HELP.
But antigen (case) need to be PRESENTED first by APC police.
APCs need to digest their cases and put it nicely on a MHC plate.

Dendritic cell Neutrophil Macrophage

(main duty: (patrol the blood vessels) (patrol the tissues)
antigen presentation)
APC “policemen”
NK cell
“I’m not doing antigen presenting.
My job is immunosurveillance, ADCC.”
 “SWAT team”
(Special Weapons TH 1 TH 2
and Tactics) -Like to direct -Like to ask B cell to
macrophage to work produce IgM & other
-Also ask B cell to antibodies
produce IgG to
enhance phagocytosis

Acquired level: Cytotoxic T

cell (CTL)
- A bit like boss
(also a T cell)
B cell - Cloning more of
Presenting himself as
cases (Antigen) SPECIFIC troops
actually to for SPECIFIC
PLASMA CELL pathogens
TWO bosses
Shoot antibody
bullets
One clone shoot
one type of bullet
to kill one specific
type of pathogen
“CTL troops”
Each specialized to attack one
Antigen coated
Innate level:

with “bullets “ specific pathogen, & kill them

for opsonization using cytotoxic “chemical
(enhance weapons”
phagocytosis)

NK cell
Dendritic cell Neutrophil Macrophage Using antibody to kill via cytotoxic
chemical weapon
APC “policemen”
IMMUNE SYSTEM

END OF PRESENTATION

Next: Applications of immunology

APPLICATIONS OF
IMMUNOLOGY
IMMUNE DISORDERS
Immune responses are mostly beneficial, but they can be harmful

To understand the disorders, we must know the normal immune

responses. Let us revise …
 The immune system gone wrong

• Understanding the adaptive immune response is

important for the control of:

• Allergies

• Organ graft rejection

• Autoimmune disease

• Immunodeficiency

• Cancers
3
 Allergy &
hypersensitivity

4
 Hypersensitivity
Hypersensitivity is a adverse reaction
(symptomatic) to a normally innocuous
(harmless) environmental antigen

Allergy (Hypersensitivity
• Antigen can interact with antibody lead Type I) to seafood

to Type I, II & III

• Antigen can also interact with T cells to
cause Type IV
• In other word, hypersensitivity types are
classed by their mechanism Reaction to TB vaccine
(Type IV)
5
 Hypersensitivity Type I
(= allergy; immediate hypersensitivity)
Allergic reactions occurs when an individual has IgE
against certain environmental antigen.

IgE normally bound to mast cell.

The binding of antigen to IgEs activates mast cell to
release chemical mediators/histamine, lead to
inflammation

Different allergens, route of entry & doses determine

the different types of allergic reactions (see next
slide)
Inflammation:
- ↑ blood flow
- ↑ fluid in tissue
- ↑ mucus >> block airway 6
- ↑ fluid in intestine >> diarrhea
Hypersensitivity Type I:
Symptoms varies according to route of entry & doses

7
Have some ideas on common allergic syndromes
 Hypersensitivity Type II
• For some people, antigen such as penicillin can bind to the surface of cell (i.e. RBC)
• The membrane bound antigen attracted IgG
• And the Fc of IgG attracts macrophage, which come & destroy the RBC (=haemolysis)
• Can also bind to other cells, and non cells i.e. platelet, matrix

Haemolysis

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 Hypersensitivity Type III
▪ Antigens are normally soluble
▪ But if antigen forms complexes with IgG, they become insoluble
▪ This “deposits” can cause Type III
▪ E.g. Arthus reaction. The person has IgG in the tissue but doctor doesn't know.
▪ Doctor inject something that contain the antigen, the antigen form complex with IgG
in tissue.
▪ Fc tail of IgG can bind to Fc receptors of mast cells & other WBCs, blood vessel
become permeable, inflammation will happen.

9
Antibody – complement system - inflammation

Good Bad
Antibody – complement system - inflammation

Good Bad

C5a
 Hypersensitivity Type IV (Delayed type)
> Type IV are T cells mediated, e.g. tuberculin reaction
T helper cells already Macrophages release more cytokines >>>
present and “learned” to more macrophages & more fluid >>
recognize antigen due to severe inflammation
previous exposure.

Antigen of They activate macrophages.

Mycobacterium
used to inoculate
the skin to test if
positive for TB

Macrophage
recruitment

iNOS: inducible nitric oxide synthases, signalling molecule for autoimmune

T helper cell

Good Bad
Hypersensitivity Type IV (Delayed type)

> Three types

– TH 1 cells e.g. tuberculin
reaction
– TH 2 cells e.g. chronic
asthma
– CTL e.g. graft rejection.

14
 Hypersensities – Which one is Type I, II, III or IV …

Inflammation is out of control !

Antigen IgG Macrophages Antigen

IgE IgG

Antigen

Antigen

• Type I (=allergy):
• IgE + mast cells + histamine = serious inflammation!
• Type II:
• Innocuous antigen (e.g. penicillin) binds to surface of RBC/platelets > WBC
though it is foreign protein or pathogen > phagocytosis of RBC/platelet >
serious inflammation
• Type III: antigen + antibody = complex > kick starts classical pathway of
complement system > release C5a > inflammation
• Type IV: macrophage > chronic phagocytosis + inflammation
 Hypersensitivities - SUMMARY

IgG

Compare & contrast as much as you can

How is Type I different from Type II?
Covid-19 Cytokine Storm

COVID-19 infection can be

accompanied by an aggressive
inflammatory response with the
release of a large amount of pro-
inflammatory cytokines in an
event known as “cytokine storm”.

The host immune response to

the SARS-CoV-2 virus is
hyperactive resulting in an
excessive inflammatory reaction.
 Autoimmunity

• Happen in some people

• Diseases that caused by the adaptive immune response
to self antigens are called autoimmune diseases

18
Autoimmunity
Is it due to
antibody?

Autoantibodies activate the

receptor of thyroid-stimulating hormone Yes

No

No

No

Yes (also
T cells)

19
 Autoimmunity – Type I diabetes

Pancreas is an unique organ that is both producing enzymes and hormones!

Digestive:
• Acinar cells produces enzymes to digest carbohydrate, protein and fat.

Endocrine:
• Alpha cells produce glucagon (more glucose release into blood)
• Beta cells produce insulin (more glucose absorbed from blood)
• Delta cells produce somatostatin (control acid secretion in stomach, etc.)
Immunodeficiency

21
 Immunodeficiency
• Immunodeficiency are disorders in which the ability of the
immune system to protect against pathogens is defective
or absent.

SCID “bubble boy”

• These can be either:
> “inborn immunodeficiency” which results from
genetic or developmental defects in the immune
system
> “acquired immunodeficiency” which develops later in
life following exposure to chemical or biological agents

22
 Inborn Immunodeficiency

• No/lack of immune system cells or specific proteins i.e. antibodies or

complement system proteins
• Example:
• Severe Combined Immunodeficiency (SCID) – no lymphocytes, cannot
SCID “bubble boy”
develop acquire immunity

• Can cause death during infancy

• Unless treated - bone marrow transplants & stem cell transplants

23
 Acquired Immunodeficiency
• Acquired immunodeficiency results from exposure such as:
> Immunosuppressants (drug) given for organ transplant patient
> Chemo & radio therapy given for cancer treatment patients (the
therapy stops all cells from dividing, including B & T cells that are
important for immunity)
> Pathogens that infect the immune system (i.e. Human
Immuodeficiency virus (HIV)
> Pathogens that cause latent infection in immune cells (i.e. HIV &
Epstein–Barr virus)
> Cancers such as Hodgkin’s disease, which damages the lymphatic
system

24
APPLICATION OF
IMMUNOLOGY
 Applications of immunology for human
disease

• Several applications of immunology are:

> Diagnosis of disease – e.g. by detecting the level of antibody in the blood

> Treatments of autoimmune diseases such as multiple sclerosis

> Vaccines

> Organ donations

> Blood typing

26
Applications of immunology

BLOOD TYPING

27
 Blood typing
• Blood group antigens are surface molecules on RBC that are detectable
using antibodies
• Major blood group antigens are ABO & Rh (rhesus)
• However, there are many other minor blood group antigens (over 50
different proteins have been identified on the surface of human RBC’s)

GlcNAc: N-acetylglucosamine
GalNAc: N-acetylgalactosamine
Gal: galactose
Fuc: fucose

28
 Blood typing
• These glucosamines also naturally present in bacteria, pollen, etc.
• Prior exposure to these antigens (e.g. bacteria, etc.) causing our body to
produce anti-A and anti-B antibodies. This explain why people with blood
type O “somehow” has anti-A and anti-B antibodies.

GlcNAc: N-acetylglucosamine
GalNAc: N-acetylgalactosamine
Gal: galactose
Fuc: fucose

29
 Blood typing
• Humans & many primates can be typed for the ABO blood group.

• There are 4 principal types: A, B, AB, & O.

There are:
• 2 antigens (A & B surface proteins) &
• 2 antibodies (anti-A & anti-B antibodies)

30
Agglutination
 Blood typing

Type A Type O
Universal donor

Blood with antigen A Blood without antigen

Antibody anti-A (No) Antibody anti-A (Yes)

Antibody anti-B (Yes) Antibody anti-B (Yes)

Type A can donate Type B can donate Type AB can donate 32

blood to type A and blood to type B and blood to type AB
type AB type AB
 Blood typing

Type A Type O Type A Type O

Blood with antigen A Blood without antigen

Blood with antigen A Blood without antigen
Antibody anti-A (No) Antibody anti-A (Yes)
Antibody anti-A (No) Antibody anti-A (Yes)
Antibody anti-B (Yes) Antibody anti-B (Yes)
Antibody anti-B (Yes) Antibody anti-B (Yes)
 Blood typing
• This is important to prevent transfusion of incompatible blood

• Incompatible blood can cause a transfusion reaction where

> The presence of antibodies from donor will destroy RBC from recipient and
vice versa
> The destroyed RBC releases haemoglobin into plasma which can become
toxic

• Blood typing is also used during pregnancy to determine if a mother & unborn
child carry Rh antigens

34
 Blood typing & cross matching

• Blood typing is used to determine whether

donor & recipient have compatible ABO & Rh
blood group antigens before blood
transfusions

• A cross-match where serum from the donor

is tested on the cells of the recipient & vice
versa
• This is to rule out any other incompatibilities

Blood typing is not cross matching ! 35

 Blood typing & cross matching

Blood typing or
Blood ABO typing

= Anti O

Blood typing is not cross matching ! 36

Applications of immunology

VACCINATION

37
Rabies vaccination for dogs
 Vaccines
• Why are they important:

> For prophylactic (=prevention of disease) - prevent some infectious diseases &
cancers
> For therapeutic treatment
> For treatment of autoimmune disease

40
 How do vaccines work
▪ To prevent a viral infection, you need to
trigger the adaptive immune response
prior to the infection

▪ Vaccine fools the immune system into

thinking they have already seen the virus
& inducing a memory response

▪ Antigen presenting cells (APCs) present

the vaccine antigens to helper T, leading
to activation of T & B cells, thus provided
protection from the disease

41
 How do vaccines work
▪ Vaccine induces a “primed” state in the vaccinated subject. In the following
exposure, a rapid secondary immune response will be generated

▪ Success depends on the generation of memory T & B cells & the presence
neutralizing antibody and/or T cell in the serum (depending on the disease)

42
 Current Antiviral Vaccines
Vaccine Viral Pathogen Vaccine Type

HAV vaccine Hepatitis A virus Inactivate

HBV vaccine Hepatitis B virus Subunit/Virus like particle
HPV vaccine Human Papillomavirus types 16 Subunit/Virus like particle
and 18
Influenza vaccine Influenza type A and B viruses Inactivated/Attenuated
Japanese encephalitis vaccine Japanese encephalitis virus Inactivated/Attenuated
MMR vaccine • Measles Virus Attenuated
• Mumps Virus
• Rubella Virus
Tick bourne encephalitis Tick Bourne Encephalitis (TBE) Inactivated
virus
Rabies Vaccine Lyssavirus Inactivated
Rotavirus Vaccine Rotavirus Attenuated
Shingles/Chicken pox vaccine Varicella zoster Attenuated
Small pox vaccine Smallpox Virus Attenuated
Yellow fever vaccine Yellow fever virus Attenuated
Polio Vaccine Polio virus Inactivated/Attenuated 43
 Current Antibacterial Vaccines
Vaccine Bacterial Pathogen Vaccine Type

Anthrax Bacillus anthracis Attenuated

Diptheria Toxiod Corynebacterium diphtheruae Subunit (toxin only)

Haemophilus influenzae Haemophilus influenzae Subunit (capsid protein only)

Salmonella enterica serovar Inactivated, Subunit,

Typhoid Fever Typhi Attenuated

Cholera Vibrio cholerae Inactivated

Plague Yersinia pestis Inactivated (no longer in use)

Pneumococcal Streptococcus pneumoniae Subunit

Meningococcal Neisseria meningitidis Subunit (not great protection)

Pertussis Bordetella pertussis Attenuated

Tetanus Toxoid Clostridium tetani Subunit (toxin only)

BCG (Bacille Calmette-Guerin) Mycobacterium tuberculosis Attenuated

44
BCG – for Tuberculosis
Hepatitis B
DTaP – diphtheria + tetanus + pertussis
IPV – inactivated polio vaccine
HiB – haemophilus influenzae type B
MMR – mump + measles + rubella

Most parents also add on:

- Pneunomoccus (Streptococcus pneumoniae) 13 strains > 23 > … 90++ ?
More on vaccine under:

PEH20005 Communicable disease control

- Immunization schedule
- Common vaccines – BCG, polio, etc.

BIO30004 Molecular Biotechnology

- How to produce conventional vaccines i.e. polio
- How to produce new vaccines i.e. Dengue vaccine