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Introduction to

Immunology

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What is the Immune System?

A macrophage engulfing bacteria

An Immune system protects the

body from infection What is a Pathogen?

An infectious organism that cancause disease.

Examples: Bacteria

Fungi

Viruses

Parasites Are Humans the only ones with an

Immune system?

No, other animals, plants, fish,reptiles all have immune systems

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What happens when we get an infection?

There are 2 components of the

immune system:

1. Innate Immunity: Present in all animals

Rapid response

Non-specific

2. Adaptive Immunity

Present only in vertebrates

Slow response Specific

Generates memory for faster

recognition on second attack

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PHAGOCYTES attempt to engulf

a rose thorn inserted into the

transparent larva of a starfish.

In 1882 the Russian

zoologist lieMetchnikoff first noted

this example of an

innate host defense

response.

http://www.youtube.com/watch?NR=1&v=MgVPLNu_S-w&feature=endscreen

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Innate Immunity

Courtesy of Susan Arnold, Dr. Raowf Guirguis/National Cancer Institute

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Phagocytosis

Principles of science by Nature Education

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How does the body recognize pathogens?

Principles of science by Nature Education

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How do mammals respond to infection?

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If there are several types of pathogens, do theyall look similar or different?

There are LOTS of different

pathogens.

How does our immune

system recognize them all?

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The Adaptive Immune response

B cells T cells

B cells are the cells of the immune systemthat make antibodies

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Each B cell produces a uniqueantibody that

recognizes a specificpiece of foreign material (e.g.,

pathogen)

The different antibodies are unique from each other by having

different variable regions!

Pathogens

Antibodies

B cells

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How do B cells producedifferent variable regions of

antibodies?

Our B cells can make 1011

different antibodies

100,000,000,000

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Could it be that in our DNA wehave a genefor each of these

1011antibodies?

The entire human

genome containsabout 30,000 genes

30,000

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Gene A Gene B Gene C Gene D



Every cell in your body has the exactsame genetic information encoded in

your DNA

Skin cell

B cell

Nerve cell

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Gene A Gene B Gene

C

Gene D


However, different cells havedifferent

genes turned on or off

OFF OFF OFF

OFF OFF

ON


OFF OFF OFFON

ON ON

Skin cell

B cell

Nerve cell

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How do B cells producedifferent variable regions of

antibodies?

In the DNA of B cells, specific antibody genes are turned on.

Part of the answer isthat.


OFF OFF OFFON

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How do B cells produce different

variable regions of antibodies?

We are able to make so many different antibodies

due to another phenomenon called VDJRecombination

VDJ recombinationis the process by whichV, D, and J genes are randomly selectedand combined to form the heavy and light

chains that make antibodies.

VDJ recombinationis specific to certain cells of

the immune system and does not occur in other cells

of our body.

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V

D

JV

J

o Antibodies are made up of 2 light chain proteinsand 2 heavy chain proteins.

o The genes that encode these proteins are found

in your DNA. These are referred to as V, D, and Jgenes.

V

VD

J

J

Genes that encode antibodyproteins are found in DNA

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There are 45 V, 27 D, and 6 J genes in

the heavy chain DNA sequence

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Through VDJ recombination, the cell randomlychooses 1 V, 1 D, and 1 J gene to make the heavy

chain

V34 V35 V36V37

V38

V39

V7 V8 V9 V10 V11 V12 V13 V14 V15 V16

V17

V40

D1

D2

D3

D4

D5 D6 D7

D20

D21

D22D21

D23

D24

D25

D22

In this example,

the heavy chain

DNA randomly

recombines to

join the V36 and

the D5 genes.

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V34 V35V36

V7 V8 V9 V10 V11 V12 V13 V14 V15 V16

V17

V37

V38

V39

V40D1

D2

D3

D4

D5 D6 D7

D20

D21

D22D21

D23

D24

D25

D22

The cell randomly chooses 1 V, 1 D, and 1 J gene

to make the heavy chain

In this example,

the heavy chain

DNA randomly

recombines to

join the V36 and

the D5 genes.

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V34 V35V36

V7 V8 V9 V10 V11 V12 V13 V14 V15 V16

V17

D5

Then, the

heavy chainDNA randomly

recombines to

join the D5 and J3

genes.

The cell randomly chooses 1 V, 1 D, and 1 J gene

to make the heavy chain

J3

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V34 V35 V36

V7 V8 V9 V10 V11 V12 V13 V14 V15 V16

V17

D5

The cell randomly chooses 1 V, 1 D, and 1 J geneto make the heavy chain

J3

Then, the

heavy chainDNA randomly

recombines to

join the D5 and J3

genes.

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DNA RNA Protein

Heavy chain DNA

Heavy chain mRNA

Heavy chain protein

Transcription

Translation

V36

V36

Only the V36, D5 and J3

genes are turned ON.

The remaining heavy

chain genes are turned

OFF.

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Heavy and light chain

proteins are translated

Heavy and light

chain proteins are

assembled into

antibodies within the

cytoplasm

Antibodies are

exported to the

cell surface where

they can recognize

pathogens

Antibodies made and assembled

in B-cells

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The inability of immune cells to perform

VDJ recombinationhas very serious

consequences!

Individuals with a defect

in VDJ recombination,

lack diversity in their

antibody production, and

as a result have severely

weakened immune systems

(immunodeficiency)http://en.wikipedia.org/wiki./The_Boy_in_the_Plastic_Bubble

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One B cell isnt going to release enough antibody

on its own to fight a pathogen. So it makes clones of

itself.

A cloneis an

exact

genetic copy of

another cell.

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1000 B

cells thatrecognizethepathogen

4-5 days

An activated B cell that has come in contact with itscorresponding pathogen and helper T cell will go through

clonal expansion.

Clonal expansion

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Memory B Cells

After clonal expansion,

some B cells turn into

memory B cells.

These cells will

remain in your body

for years, ready torespond immediately

if you encounter that

pathogen again.

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Memory B Cells

Memory B cells protect us from future infections

Can we take advantage of memory B cellsto prevent

ourselves from getting sick?

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How do vaccineswork?

Vaccines contain non-infectious versions of a pathogen:

Subunitvaccines

Killedvaccines

Modifiedlive

vaccines

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How do vaccineswork?

Vaccines contain non-infectious versions of a pathogen:

Subunitvaccines

Killedvaccines

Modifiedlive

vaccinesThese incomplete or weakened versions wont make us

sick, but our body will still mount an immune response

against them, creating memory B cellsin the process.

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Name some diseases we are

vaccinated against?

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H1N1Influenza

Virus

Neumann et al. Nature

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Summary

Antibodiesare proteins created by B cellsthat

bind to pathogens, a key step in our immuneresponse.

We are able to create a large variety ofantibodies using VDJ Recombinationandturning genes on and off.

B cells mount an immune response by

undergoing clonal expansion.

We are protected from future infections bymemory B cells.

Vaccinesare a method of creating memory B

ll ith t i ill

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