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J. IMMUNITYImmune system = bodys defense system
Antigen = any molecule that body recognises as foreign
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Learning Objective / Outcomes:
Phagocytes & lymphocytes: Structure, origin,maturation & mode of action
To explain meaning of the term immune response
T & B lymphocytes : mode of action, origin, function Role of memory cells in long-term immunity
Molecular structure of antibodies related to theirfunction
Active & passive immunity
Natural & artificial immunity
Vaccination
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4co
mponents
ofblood???
1
2
3
4
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White Blood Cells/ Leucocytes (0.5%):
Lifespan: (varying)Contents: Phagocytes
Lymphocytes
Function:
Immunity
- inflammation- phagocytosis- antibody production
Eosinophils, basophils
Monocytes/macrophages
neutrophil
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Blood cells
:: how to tell them apart::
RBC
- 7 m wide- nonucleus- biconcave
WBCs
Granulated Agranulated
Eosinophil- 2 x RBC- multilobe
nucleus
Basophil
- 2 x RBC- bean nucleus
Monocyte
- 2 x RBC- bean nucleus
Macrophage- 2.5 x RBC- bean nucleus
Neutrophil- 2 x RBC
- multilobenucleus
Lymphocyte- same as RBC
- oval nucleus
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Functions of WBCs
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White blood cells
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Origins - Cells of the immune system
The cells of the immune system originate fromthe bone marrow.
There are 2 groups of these cells:
i) phagocytes (e.g. neutrophils and macrophages/ monocyte)
ii) lymphocytes (T and B cells)
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Phagocytes & phagocytosis
(Non specific immune response) Phagocytes
- produced & stored in bone marrow before distributed in blood circulation- feed likeAmoeba on bacteria, viruses and dead body cells.
Neutrophils Macrophages
60% of WBC in blood (most
abundance)travel throughout the body (blood)
squeeze through the capillary wall
and into the infected tissue, engulf and
digest offending bacteria
short-lived cells released in largenumbers during infection
Larger than neutrophils
found mostly in lung, liver, kidney,spleen, & lymph nodes, rather remain
in blood
leave the bone marrow & travel in
blood as MONOCYTES then
develop into MACROPHAGES oncesettle in organs
long-lived cells which initiate
immune response by displaying
antigens to be recognised by
lymphocytes
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ingestion of invading microorganisms by certain type of
white blood cells which are phagocytic / phagocytes Phagocytes attach to microbes via microbes surface receptors
Phagocyte engulfs the microbes, form a vacuole that fuses with
a lysosome
Lysosomes destroy microbes by 2 ways:
1. Nitric oxide & other toxic forms of oxygen contained in
lysosomes poison the engulfed microbes
2. Lysozyme & other enzyme degrade the microbial
components However, some microbes can evade from the attachment &
destruction of phagocytes because their receptors are
surrounded by outer capsule. Some resistant to lysosomes.
Phagocytosis
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Cells under attack respond by
releasing histamine, attractpassing neutrophils (chemotaxis)
neutrophils move towards the
pathogen & its plasma membrane
engulf the pathogens & trap it toform a phagosome.
Inside the vacuole, digestive
enzymes are secreted to kill the
pathogen
After killing & digesting the
pathogens, the neutrophils die.
Dead neutrophils often collect at a
site of infection to form pus
Phagocytosis - Neutrophils
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Phagocytosis - Neutrophils
1. Attraction (chemotaxis)
2. Recognition & attachment
3. Endocytosis
4. Bacteria within a phogocytic vacuole
5. Fusion of lysosomes & phagocytic vacuole
6. Killing & digestion
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Phagocytosis - Macrophage
Cut antigen up that it
can be recognised by
lymphocytes
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Phagocytosis of bacteria by a macrophage
bacteria
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Smaller than phagocytes, with a large nucleus fills
most of the cell 2 types:
1. B lymphocytes ( B-cell)
2. T lymphocytes ( T-cell)
Similarities:
Both B & T cells are produced before birth in bonemarrow
Only mature lymphocytes can carry out immuneresponse.
When mature, all B & T cells circulate betweenblood & lymph
Lymphocytes
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Lymphocytes: B cells and T cellsDifferences:
B cells T cells
remain in bone marrow until
they are mature
then spread throughout the
body concentrating in lymph
nodes & spleen
Y-shape and 4 polypeptide
chain
Bind with 2 antigen
Immune system- humoral
respond
T cells mature once migrated
from the bone marrow to the
thymus gland.
2 polypeptide chain
bind with 1 antigen.
Immune system- cell mediated
respondThymus- a gland lies in
the chest just beneath thesternum
Double in size between
birth & puberty
Shrinks after puberty
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Adenoid
Tonsil
Lymph nodes
Right lymphatic
duct, entering
vein
Thymus
Appendix
Thoracic
duct
Bone
marrow Lymphatic
vessels
Spleen
Thoracic duct,
entering veinLymph node
Masses of
lymphocytes and
macrophages
Valve
Lymphatic vessel
Blood capillary
Tissue
cellsInterstitial
fluid
Lymphatic
capillary
Human lymphatic system consists of lymphatic vessels, through whichlymph travels, & various structures that trap foreign molecules. These
structures include the adenoids, tonsils, lymph nodes, spleen & appendix.Macrophages are either residents permanently in the spleen, lymph nodes &
other tissues of lymphatic system to combat infectious agents or migrate
throughout the body.
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???
State the sites of origin & maturation of B cells & T cells.
Suggest why the thymus gland becomes smaller after
puberty.
Origin: bone marrow
B cell mature in bone marrow; T cell mature in thymes gland
By puberty, T cell have matured and left the thymus gland. Thus, thymus has
no further use so it decrease in size.
NKC k b
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Immunity
There are 2 major kinds of defense:
1. Innate Immunity External defenses & Internal defenses
2. Acquired Immunity
Overview ofvertebratedefensesagainstpathogens
NKC- non phagocytic WBC,
patrols in body,
performs apoptosis
Phagocytes & NKC
Lymphocytes
NKC work by
undergoes
apoptosis
which is burst
together with
the bacteria
Cytotoxic T-cells (Killer T-cells)
Only B-cells can secrete
antibodies.
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How do lymphocyteswork? Antigen Recognition
2 main types of lymphocytes:
B lymphocytes (B cells): helper B cell
T lymphocytes (T cells): cytotoxic/ killer, helper T
Both circulate through blood & lymph, concentrated inlymphoid tissues
Posses many identical antigen-specific receptors which
embedded in their plasma membranes can recognizesame epitope(name) of antigens or closely related antigens
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B Cell Receptors
A Y-shaped molecule
Consist of 4 polypeptide chains: 2 identical heavy chains
2 identical light chains
These chains linked by disulfide bridges
Tail portion of molecule is the transmembrane regionanchors
receptor in the cells plasma membrane
Short region at the end of tail extends into cytoplasm
Variable regionsamino acid sequences vary extensively from 1 B
cell to another
Remainder of the molecule made up of constant (C) regions Each B cell receptor has 2 identical antigen-binding site
Interaction with antigen stabilized by multiple non-covalent
bonds between chemical groups on molecules
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Immunoglobulins
An antibodies secreted by lymphocytes
Structurally similar to B cell receptors
But lack of the transmemberane regions that anchor
receptors in plasma membrane
Thus, B cell receptors also called = membrane
antibodies / membrane immunoglobulins
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Consists of2 different polypeptide chains ( and
chains) linked by disulfide bridge Transmembrane region anchors the molecule in the
cells plasma membrane
Out tip of these chain are variable (V) regions, form a
single antigen binding site
Remainder of the molecule is constant (C) regions
T Cell Receptors
B Cell Receptorsvs
T Cell Receptors B cell receptors recognize intact antigens
T cell receptors recognize small fragments of antigens that
bound to normal cells surface proteins (MHC molecules)
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Interaction of T cells with MHC molecules
MHC
Antigen presentation
MHC Major Histocompatibility Complex
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Acquired Immune Response
Cell-mediated immune response involves the activation & clonal selection ofcytotoxic T
cells, which directly destroy certain target cells
Humoral immune response
involves the activation & clonal selection ofB cells, causes
the production of secreted antibodies which will circulate in
blood & lymph
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T cells develop surface receptors called T-cellreceptorswhere they become programmed for theantigen of their specific enemy
If an antigen is presented to a T cell with a
complementary shaped receptor, the T cell isstimulated, increases in size and starts to dividecytotoxic T cells/ killer cells + helper T cellsmemory cells
T cells reproduce rapidly, however they do notproduce antibodies like B cells
Cell-mediated immunity
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Chemical
substances
Only Active helper T-
cell will release
chemical substance
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T Helper Cytotoxic T cell /Killer T
recognise the non-self antigen
(from the foreign cells) that themacrophages display on their outer
surface.
release a powerful group of
chemicals called cytokines tostimulate B cells to proliferate
stimulate macrophages to carry out
phagocytosis more vigorously.
Cytotoxic (kill cell)
attack & kills body cells that have
been infected by virus, bacteria or
fungus.
Kill the infected cells by secretingproteins (perforin) that punch holes
in the membrane of the cell, and the
contents ooze out.
In addition to helper & killer cells, memory T cell are produced whichremain in the body & become active quickly during secondary response
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A T cell
l
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ytotoxicT
cellsattackingaca
ncercell
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A human helper T cell (green) under attack by HIV
(red spheres)
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When the pathogen first enter the body, macrophages engulf anddigest microbes (including their antigens) through a process of
called phagocytosis.
Some of the digested antigens are then displayed on the surfaces of
the macrophages. This is called antigen presentation T-helpercellsantigen presentation B cell
OR any B cells whose cell surface receptors fit theantigens, can
respond directly
B cell dividing repeatedly by mitosis& after several generations
will differentiate intoplasma cell (antibodies) + memory B cells
Humoral Immunity response
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of Humurolell-Mediatedond
by antigen,nition
mitosis
atured
s(receptor)
een Humurolell-Mediatedondcell
HC molecule
estroy
infected celldirectly (Killer-
T cell
produced
perforin)
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Memory Cells
Remain circulating in the bodies for long time/ life
time
If antigens reintroduce after 1st infection, memory
cells divide rapidly & develop into plasma cell (Bcells) or killer cells (T cells) + more memory cells
Thus, infection can be destroyed & removed before
any symptoms of disease develop
Ch i ib d i i bl d
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Changes in antibody concentration in blood
Primary
response:1st response at 1st
infection
Slow
Why?
Very few B cells
are specific to the
antigen at this stage
Take times toreplicate more
plasma cell (give
antibodies)
Secondary
response
2nd exposure toantigen
Faster
Why?
Many memory
cells available
Can quickly
divide &
differentiate into
plasma cells
Give antibodies
~15 days~8 days
************
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What is antibody? Antibodies are globular glycoproteins and form the group of
plasma proteins called immunoglobins.
A protein made by the immune system in response to the presence
of an antigen & targeted specifically at it
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Antibody Structure
Four polypeptide chains
two light chains
two heavy chains
All the chains are joint bydisulphide bond
Each chain has a variableregion
Made up of different aminoacid
Bind to same Antigen Different Antibody has
different variable region
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Hinge region.. Spring like..
The hinge region gives theflexibilityfor antibody to
bind to antigens that are
differently spaced
microorganism
antigen
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Fab and Fc Regions
Fab (Fragment antigen binding)
region contains the antigen-binding
site
Different antibody has different
antigen-binding sites Fc (Fragment crystallisable)
region
Different Antibodies have same
Fc region
Fab
Fc
Disulphide bridges
How do Antibodies Work?
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How do Antibodies Work?(1) Prevent entry (2) prevent movement (3) agglutination
(4) lysis (5) opsonisation (6)neutralisation
Four Classes of Antibodies
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Four Classes of Antibodies
monomer
monomer
dimer
pentamer
Ig GAME
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A ib d (R )!!!!
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Antibody (Recap)!!!!
Definition of antibody
Globular glycoprotein, immunoglobulin Molecular structure of antibody
4 chains: 2 light & 2 heavy chains
disulphide bridges
Antigen-binding sites : variable regions Fab (Fragment antigen binding) region& Fc (Fragment crystallisable)
region
4 classes of antibody
IgG, IgA, IgM, IgE 6 functions of antibody
(1) Prevent entry (2) prevent movement (3) agglutination(4) lysis (5) opsonisation (6)neutralisation
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??? Why polysaccharides would not be suitable for
making antibody molecules?
There are many different strains of the rhinovirus,
which causes the common cold. Explain why peoplecan catch several different colds in the space of a fewmonths.
-Polysaccharides are made from only a small number of different sugar unlike
protein that are made from 20 different amino acid.
- Polysaccharides would not give the same huge number of different molecule
shape as is achieved with protein in the variable region of antibodies.
-Immunity to one strain does not provide immunity to all of them as they do not
all share the same antigens.
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Why people are often ill for several weeks after they
catch a disease, even though they can makeantibodies against the disease?
- Because the primary respond to an antigen is slow.
- It take several weeks (usually~16 days) to produce enough antibody to
fight the infection effectively
- During this time, we usually shows the symptoms of the disease
concerned.
June 07 Paper 1
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June 07/P1
N/04
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N/06
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J/08
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J/08
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- Infection todisease
- Maternal
antibodies
- Vaccination
- Synthetic
antibodies
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Active immunity
immunity gained following infection
Because lymphocytes are activated by antigens on surface ofpathogens that invaded into the body
Activate B or T cells to give effective defense
1. Natural Active immunity
body manufactures antibodies when exposed to an
infectious agent.
2. Artificial Active Immunity
injection of antigens into body, taking by mouth
vaccination or immunisation
Does it safe?
ll d f ti i ll f b th th i
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small dose of antigen is usually safe because the pathogen is
either killed or attenuated (pathogen has being weaken)
individual does not contract the disease itself, but is stimulated to
manufacture antibodies against the antigen. second booster/ injection is given and this stimulates a much
quicker production of antibody.
Longterm
immunity
V i ti
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Vaccination
Is a preparation containing:
antigenic material (live/ dead/ harmless/ attenuatedmicrobes),
harmless toxin,
or a preparation of surface antigen
Highly effective vaccines1 injection may give alifetimes protection
Less effective vaccinesneed booster injections tostimulate 2nd respond
Does every single vaccine work?
Problems with vaccines
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Problems with vaccines
1. Poor respond
Some people do not respond well / or not at all to vaccines Because ofdefective immune system:
a) Inborn / Primary Immunodeficiency
An immunodeficiency disease caused by a genetic or
developmental defect in immune system Example: Severe combined immunodeficiency (SCID)
both humoral & cell-mediated branches of acquiredimmunity fail to function
b) Acquired / Secondary Immunodeficiency
An immunodeficiency disease that develops later in lifefollowing exposure to various chemical or biologicalagents
Example:Acquired immunodeficiency syndrome (AIDS)
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Poor respond also because ofmalnutrition
Especially protein energy malnutrition
Do not have enough protein to make antibodies or clonesof lymphocytes
Higher risk to develop infectious disease
2. Antigenic variation
Rhinovirus- colds- has at least 113 different strains
Trypanosoma- sleeping sickness- has 1000 different
antigens, & changes them every 4 or 5 days
Antigenic drift- minor changes in antigen structure,
memory cells can work
Antigenic shift- major changes
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3. Antigenic concealment
Some pathogens hide inside cells
Plasmodium enters liver cells or red blood cells,
protected against antibodies in the plasma
Some parasitic worms cover their bodies in host
proteins, invisible to immune system
Some pathogens parasiting the macrophages & T
cells
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Passive immunity
immunity gained by antibodies made other than in the host
1. Natural passive immunity
Antibodies made in one individual are passed into another
individual of the same species.
Mother fetus
Antibodies from mother cross the placenta during
pregnancy, remain in the infant for several months
Example: Ig G ( circulates in the blood, prevent the growthof bacteria & virus)
Explain the pattern of maternal & infant IgG.
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Concentrations
of antibody in
the blood of
fetus & an infant
Maternal IgG increases during pregnancy as it crosses the placenta (natural passive
immunity)
It decreases after birth as it is removed from the circulation
Fetus does not produce its own antibodies because does not have mature T/B cells,
& is kept in sterile environment
Infant produces its own antibodies shortly after birth as it begins to encounter
infections
fetus
2 A tifi i l i i it
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2. Artificial passive immunity
Antibodies which have been made in one individual are
extracted and then injected into the blood of another
individual which may, or may not, be of the same species
Tetanus: kills quickly, body needs immediate defense
a prolonged contraction of skeletal muscle fibres, bacterial
infection at wound contamination.
Injection of antitoxin: provides immediate protection but
only temporary. Why?
Antibodies not produced by the bodys own B/T cells &therefore regarded as foreign
Will remove from circulation by phagocytes in the liver &
spleen (No memory cells)
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Immunity Antigen
encountered
Immune
respond
time before
antibodies
appear in blood
Production of
memory cells
protection
Active yes yes Several week yes long term
Passive no no immediate no temporary
???
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???What are the difference between artificial active immunisation
(vaccination) and artificial passive immunisation?
Artificial Active Imm Artificial Passive Imm
Antigen are introduced into the
body by injection/ by mouth
Antibodies are injected into the
body
To stimulate an respond by B /
T cells
Temporary /Short-term
immunity, no immune respond
Gives a long term immunity
(memory cells are generated)
Temporary/ short-term
immunity, remove from
circulation soon
But respond not immediate Gives an immediate respond
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Pass Year Questions J
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Pass Year Questions - J
O/N 08/ P2 No.1
O/N 05/P2 No.4 (c)
M/J 04/ P2 No. 6
O/N 03/ P2 No. 3, No.5 (c) and (d) O/N 02/ P2 No. 5