j immunity defense sys.student

7/30/2019 J Immunity Defense Sys.student

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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

j immunity defense sys.student

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