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Introduction to the Immune

Response
Session 1 Immunology 5 ONPS2294
Danilla Grando
Reference: Nester 4th, 5th ,6th Chapter 15 intro, 15.1, .2, .3,
.7 Chapter 16 intro and 16.1
Nester 7th Chapter 14 intro, 14.1, .2, .3, .7 Chapter 15 intro
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and 15.1

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Introduction to immunity

We live in an environment of microorganisms


So why dont we get sick all the time?
A human that survives the encounter probably
does so because of an intact immune response
The immune response can be viewed as three
lines of defence

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First line of defence

Consider you are under attack by invaders


What would be your first line of defence?
A physical barrier helps as well as chemicals
that you can throw on the invader

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Antimicrobial aspects of physical
first-line defences
Desquamation and dryness
Fatty acids secreted by sebaceous glands
(lower pH)
Mucociliary escalator

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Antimicrobial aspects of physical
first-line defences
Anatomical features
e.g. curvature of
respiratory tract, cough
reflex, eye-lashes,
drainage of urinary
tract or tears

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Problems
Desquamation leads to organism dispersal, e.g.
Staphylococcus aureus, Chicken Pox
Some organisms can multiply to large numbers in sweat
glands, blockages can result in abscesses, e.g. Staph.
aureus boils
Mucociliary escalator damaged by smoke, cilia sleep
too with anaesthetics
As we age our anatomy changes or is damaged, e.g
prolapsed bladder, blockages of tear ducts, chronic
cough

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What would be a symptom?

1. Tear film
2. Drains to
lacrimal
duct, may
get blocked
3. Babies
may have
malformed
naso-
lacrimal
duct

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Antimicrobial activities

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Antimicrobial aspects of chemical
first-line defences
The tear film and saliva has an antibacterial enzyme
called lysozyme
Acid (HCl) present in stomach
Lactobacilli make Lactic acid in vagina
Special antibodies present on mucus membranes
(IgA)
Bacteria in mouth and bowel compete for food and
do not allow overgrowth of any one bacteria or
yeast

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Sites of
Nose normal flora
Mouth
Throat
Stomach

Small intestine

Large intestine
Perineal skin
Vagina

Opening of
urethra

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Sites that should remain sterile

Bladder (UTI)
Lung (Pneumonia)
Blood (Bacteraemia and Septicaemia)
Cerebrospinal fluid CSF (Meningitis)

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Problems

Lysozyme limited usefulness as not effective if


plaque or blockages in eyes
Stomach acid neutralised by food and ingested
chemicals
Lactobacilli may be lost in the vagina
Bacteria can break down antibodies
Bowel bacteria may be lost on antibiotic
treatment leading to over-growth

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Lactobacilli stuck to vaginal Lactobacilli lost, other


epithelia smelly bacteria grow

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The second line of defence

Also has a physical and chemical aspect


This time the physical = non-specific immune
cells
There are a large number of non-specific
immune chemicals
These cells and chemicals cannot tell one
pathogen from another

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Non-specific immune cells
Neutrophils (name given to them in blood stream) migrate
into tissue and are called polymorphs
(polymorphoneutrophils or PMNs)
Large numbers congregate at the site of tissue damage =
pus and these are phagocytic
Dendritic cells are also phagocytic
Monocytes (blood) migrate to tissue (macrophages)
and also phagocytes
Natural Killer cells look like large lymphocytes but are
actually granulocytes, non-specific but act differently from
phagocytic cells

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How do phagocytes do their job?

They are attracted to surface


molecules on bacteria
They are also attracted to
other immune signals (see
specific immunity later)
The prefix phago comes
from Greek to eat

A phagocyte eating a bacteria

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Telling a neutrophil from a monocyte

Polymorphs or neutrophils have a many shaped


nucleus, when they are young, called band-form

RBC
Neutrophil lymphocytes

band-neutrophil
Monocyte

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Process of phagocytosis

Bacteria are ingested, broken down and then


pieces are placed on outside of the phagocyte

Enzyme packets

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Granulocytes

Activated neutrophils (PMNs) and monocytes


(macrophages) have visible granules which are
the enzyme containing packets that fuse with
phagosome
Basophils (blood) and mast cells (tissue) have
granules that contain histamine
Eosinophils release their granules onto parasites
NK cells also have packets but these are release
on binding a target cell

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Granulocytes

Basophil Neutrophil Eosinophil

Mast cells in
tissue

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Dendritic cells

Develop from monocytes but have a spiked


appearance and have Toll receptors
In various tissues in the body and can present
antigen
Toll-like
receptors

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Antigen Presentation

The pieces of protein placed on the outside of


macrophages are called peptides
These peptides have a shape that can be
recognised by the immune system and thus are
called antigens
Blood cells have antigens on them, e.g A, B, Rh
factor
One bacterium may have a number of different
antigens, e.g parts of its wall, swimming tail

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Chemicals of the second line of
defence
Interferon used by cells to signal imminent viral
attack

Interferon leaves
infected cell,
signals
neighbouring cells
Cell then makes anti-viral protein

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Problems with interferon

When discovered, thought to be the magic bullet


against viral infections
Synthetic interferon only small effect
Now know interferon needs to be made in
vicinity of infection
Interferon therapy for Hepatitis C has had some
success in slowing damage

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Chemicals of the second line of
defence
Complement proteins present in blood stream
punch holes in bacteria and help coat bacteria
and mark them for destruction
Complement proteins also help trigger the
process of inflammation
People can be deficient in complement and be
more susceptible to bacterial infections

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Inflammation

What are the four signs of inflammation?


Redness
Swelling
Pain
Heat
How can you explain these symptoms?

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Process of inflammation

Tissue damage causes subcutaneous mast cells


to release histamine
Histamines causes
capillaries to swell
and become
leaky Mast cell
releases
histamine

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Inflammation continued

Histamine and other chemical signals cause


neutrophils to extravasate and are attracted
(chemotaxis) to site of injury

Endothelial cells
line capillaries Bacteria
at site of
injury
Neutrophils
Chemotactic signals

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Questions

Now explain the fours signs of inflammation


based on what you understand about
inflammation at the cellular level

Explain why there is pus at the site of injury

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Specific immunity

Ist and 2nd lines also called Innate Immunity


3rd line of defense called specific or adapted immunity
We are not born with this, our immune system learns
to recognise one pathogen from another
It remembers it has seen the pathogen before
It responds very fast the next time it meets a pathogen
it has met before
It knows what is foreign and what is self

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Elements of specific immunity

There are cells, e.g. lymphocytes


And chemicals, e.g. antibodies

Some of the lymphocytes can kill, this is called


cellular immunity

The antibodies can mark foreign material for


destruction, this is called humoral immunity

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Two arms of the immune response
Response to infection can be humoral or cellular

Antibody

Cytotoxic
T-lymphocyte

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Questions

Why have two arms of specific defence

Which would cause more damage in the body?

Tuberculosis bacteria get inside macrophages


and stop them from doing their job. Explain why
lung damage occurs.

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How do Cytotoxic T-cells do their
job?
When a cell is infected with an intracellular
organism, cell moves some of the organisms
proteins to the outside of the cell
Cytotoxic T-cell that has a receptor that
recognises the protein, locks on
This creates a signal that makes the T-cell divide
Army of cytotoxic T-cells lock onto infected host
cells and kill them (causes lots of damage)

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Helper T-cells

Signals are very important to the immune system


Helper T-cell influences whether killer-T cells or
antibodies needed
Helper T-cells get attacked by HIV so immune
system fails

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Where do antibodies come from?

You are exposed to and infectious agent or


better still, a vaccine
A B-lymphocyte that has a receptor that
recognises the protein, locks on
This creates a signal that makes the B-cell divide
Army of B-cells with same receptor
Some become memory cells, others become
antibody producing factories called plasma cells

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How do antibodies work?

The arms of the antibody can recognise a shape


Proteins have shapes and are present on most
cells
The body is able to generate Protein
antibodies that recognise
any protein

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Antibodies bind
After antibodies have bound to an antigen, their tail
becomes attractive to macrophages

Antigen can be virus, toxin or bacteria once bound by


antibody, no longer able to cause disease

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