How your immune system is fighting for you | Julia Jellusova | TEDxFreiburg

Did you know that we live in a dangerous world? We are surrounded by viruses and bacteria, and the only reason why we survive is our immune system! In her humorous talk, Julia Jellusova, a biologist focusing on immunology, explains the role of B cells, and what toymaking has to do with our immune system. Using interesting examples, she explains the importance of further research on B cells, and how our body can even fight cancer. Julia Jellusova is a scientist in one of the University of Freiburg’s new Excellence Clusters: CIBSS - the Centre for Integrative Biological Signalling Studies. Her research group focuses on how the metabolism of immune cells controls their function and their ability to fight infection and cancer. She also explores how defects in the immune system can lead to autoimmune disease.

Julia has a passion for sharing her fascination with the immune system with young scientists and with the public. Aside from her research activities, she is also a writer and illustrator of children’s books, including a recent book entitled "Entdecke dein Immunsystem" [Discover Your Immune System].

This talk was given at a TEDx event using the TED conference format but independently organized by a local community. Learn more at https://www.ted.com/tedx

So, good evening Freiburg.

I don't know if you are aware of it,
but we live in a dangerous world.

We are surrounded by millions and millions
of bacteria and viruses.

They're everywhere.

They're in the air, they're on our skin,

they're in our food.

And the only reason
why we don't get sick all the time

is because we have our immune system.

(Laughter)

The immune system consists of
different types of cells

that can recognize and destroy bacteria,
viruses, worms, even cancer cells.

These cells swim through our blood,

and they patrol our body
for invading pathogens.

You might think this is
an easy task to do, right?

How hard can it be to tell
that we have been infected?

I mean, this is clearly different
from our own body, right?

But actually, it is pretty difficult

because these are the -

these are the cells of your immune system,

these are the little soldiers
fighting in your army.

They have no eyes, they have no hands,

and even if they did have eyes,

it wouldn't be so easy
to tell good apart from evil.

This is something the cells might see
when they travel through your body.

And what do you think this is?

Is this a normal cell,
or maybe it's a cancer cell?

Or is it a cell that has been
infected with a virus

and is now spewing
millions of virus particles?

And how about this thing?

Is this a bacterium
that wants to make you sick,

or is it a bacterium that wants
to help you digest your food?

Or maybe it's just some dust?

So, you see, it's not
that easy to tell, is it?

So how does our immune system do it?

Well, to explain this to you,

let me introduce you to one of the cells
of the immune system, the B cell.

Maybe you already know these cells.

These are the cells
that produce antibodies,

and these are the cells that work for you
when you get a vaccination.

So, this is what they look like.

They have the so-called
B-cell receptors on their surface.

These are proteins that help the cell
communicate with the environment.

They are like little hands

that help the cell feel around
and discover what's out there.

But unlike your hands,

these B-cell receptors
can recognize only one structure.

So, for example, this B cell
would be able to recognize

this red spiky protein,

but it wouldn't be able to recognize
the blue, bumpy protein.

And this is a problem, right?

Because there's millions
of different bacteria and viruses,

and if we only had
this one type of B cell,

we would be only able
to recognize this one bacterium,

and all the other ones would make us sick.

So, what's the solution?

Well, of course, to have B cells
with different B-cell receptors.

And, in fact, we have millions of B cells,

and every one of them is carrying
a different B-cell receptor

and can recognize a different bacterium.

So, no matter with what you get infected,

there always is a B cell
that can sound the alarm

and tell the body something is happening.

But how is that possible?

How is it possible that we have
so many different B cells?

How is it possible that we can
recognize all the bacteria

that we meet at home,

and also all the bacteria that we meet
if we travel to foreign countries?

I mean there are a lot of -

(Laughter)

there are a lot of bacteria out there.

So, how do the cells do it?

So, this is how your body works.

If you want to make a protein,
you need to have it encoded in your DNA.

So, every protein in your body
is encoded by a stretch of your DNA,

which is called a gene.

You can imagine the DNA
to be like a library,

full with information
on how to make a functional human body.

So, every protein in your body
is encoded by your DNA,

and every single cell in your body
is carrying the same DNA.

And now you might think,

"Oh, this sounds strange,

I mean I have all these different cells

which look different
and have these different functions,

how is it possible
that they all have the same DNA?"

And the trick is that although they have
the same information,

they use it differently.

So, they read different information,

and only read the ones
they need for their work.

So, that is as if a baker
and a car mechanic

were to own the same library.

The baker would read
the books on how to make cakes,

and the car mechanic would read
the books on how to fix cars.

So, this is the same with your cells.

The cells from your eye
will read the information

on how to make light-sensitive protein
that helps you see,

and the cells of your liver

will read the information
on how to get rid of the alcohol

that you keep mysteriously
poisoning yourself with.

(Laughter)

But all of these cells have the same DNA,

they just use it differently.

Now, coming back
to the problem with the B cells,

if you wanted to make
a million different B-cell receptors,

you would need a million different genes.

And this is certainly quite a lot.

So, currently, a human cell
has 20,000 genes,

and if you were to add
a million on top of that,

your cell would be chock full with DNA,

it would be bursting with DNA.

So, this is clearly
impossible to accomplish,

yet we do have millions
of different B cells,

with different B-cell receptors.

So, how do the cells do it?

They have developed a simple strategy:

instead of encoding
the B-cell receptor with one gene,

what they do instead is

they put it together
from different pieces.

These pieces are called
the V, D, and J segments.

The cells have different
variations of these pieces,

and then they randomly assemble them
and make their B-cell receptor.

And because this process is random,

you always end up with
a different B-cell receptor.

So, in case you're now confused,

and you don't understand
how this strategy works,

don't worry, I will explain it
with another example.

So, imagine yourself
in the business of toymaking.

Your boss gives you three blueprints
on how to make toys.

These blueprints have information
on how to make the head,

and how to make the body,

and how to make the feet,

and you set to work and you make
a nice business bear,

and a ballerina doll, and a butterfly.

You're very happy with yourself,

and you want to keep on and make new toys.

But then your boss tells you,

"I'm sorry, but you know,
the shelf for storing blueprints

only has space for three blueprints,

so this is all you get."

So, what could you do now?

What could you do to make more toys?

You could cut

these blueprints into pieces,

and then you could randomly pick
pieces to make new toys.

This way you would get
this wonderful butterfly bear,

you would get a ballerina doll
who is also a businesswoman,

and you would get a butterfly
wearing baggy pants,

and a butterfly wearing a skirt.

You would have all these new toys,
although you only have three blueprints.

So, this is exactly
what the B cells are doing as well.

They have these different
variations of these parts,

and they randomly assemble them.

And if you remember
your math lessons from school,

if you had 3 variations
for all these 3 segments,

you could make 27 different
B-cell receptors,

but if you had 100 variations
for every of these segments,

you could make a million
different B-cell receptors.

This would clearly
save you a lot of space.

You would only need 100 DNA stretches,

but you could randomly assemble them

and get a million
different B-cell receptors.

And the second strategy the cells use is

they introduce small
mutations into the DNA.

By introducing mutations into the DNA,

they slightly change the protein,

and this way they have
another new B-cell receptor.

This is similar to if you were
to randomly doodle on your blueprint

and make small changes.

And then, you could go
from a bear to a pig.

So, this is what the cells
are doing as well:

they introduce small changes

and then end up with
a slightly changed B-cell receptor.

So, these two strategies are so successful

that we have millions of B cells

and each of them carrying
a different B-cell receptor.

So, all of these cells have the same DNA,

they have the same information,

but because they randomly assemble
their B-cell receptor,

and because each of them
is making the decision by itself,

they all end up with
a different B-cell receptor.

This way you have B cells
that can recognize

any type of pathogen in the world.

This strategy is so successful
that you even have B cells

that can recognize proteins
that don't exist yet.

So, even if we get invaded
by alien bacteria,

we still have a B cell that would be able
to recognize this bacterium

and sound the alarm.

But maybe now you can see
the problem, right?

I mean, if you produce something
by just randomly assembling parts,

you might end up with
something you don't want.

If you randomly assembled doll parts,
you might end up with this.

I mean it's hideous,
nobody would want to play with that.

(Laughter)

And this is the same for the B cells.

They might end up with
a B-cell receptor they don't like.

So, a B-cell receptor we don't like
is one that recognizes our own protein.

Because our own cells
are also made out of protein,

and if a B cell binds
to any of these proteins,

it will target the cell for destruction.

So, nobody wants an army like that, right?

Nobody wants an army
that destroys all the enemies,

but then continues on
and destroys all the friends as well.

So, you know, there must be a strategy

for how to silence these cells,

or how to remove them.

And this is where things get
a little bit difficult and complicated.

But what the cells
of your immune system do

is that after they have
recognized a protein,

they don't attack right away,
but first they analyze the situation.

They ask a lot of questions.

They ask, for example:

Was there a wound when I saw this protein?

Was the skin broken?

Did I see a lot of it, or just a little?

Was it just freely floating around,
or was it on the surface of something?

Did other cells see this
as dangerous as well?

This is what we are studying in my lab,

and this is what a lot of labs
in Freiburg study as well.

We are trying to understand
how B cells receive information,

how they communicate with other cells,

how they analyze this information,

and then how they make their decisions.

And if you understand
the language of the immune system,

you know, this is very useful,

because you can talk back
to your immune system,

you can tell it what to do.

This can be useful in many
different types of diseases.

So, for example, during autoimmunity,

if you are suffering
from an autoimmune disorder,

such as lupus, rheumatoid arthritis,

or multiple sclerosis,

what happens in your body

is that the immune system
misunderstood something,

that it misunderstood some information,

and it's now attacking your own cells.

And similarly in allergies.

If you get an allergy, your immune system
misunderstood some situation,

and now thinks harmless stuff,
such as dust and pollen,

is actually dangerous.

So, what you want to do
is you want to tell your immune system

just to quiet down.

And this is exactly what you're doing
if you get an anti-inflammatory drug:

this is your way of telling
your immune system

just to shut up, you know, keep it quiet,

this is not as dangerous
as you think it is.

And then on the other side,

there are diseases where you want
your immune system to be more active.

So, every time you get an infection,

every time you, for example, get the flu,

what happens is that your immune system

either didn't recognize the pathogen,
or decided it's not dangerous,

or was just too slow in responding.

So, what you want to do here is

you want to tell the immune
system to be more active.

And this is exactly what you're doing
when you get a vaccination.

When you get a vaccination,

you get injected
with a tiny piece of protein,

and this is basically
a heads up to your immune system.

It tells your immune system,

"This is dangerous, you might
see it in the future, get ready."

So then, later on, when the immune system
really sees the real pathogen,

it will respond much faster
and much more strongly.

So, vaccinations are the most elegant
type of treatment there is.

I mean, think about it,

if you're treating an infection
with antibiotics,

you have to take antibiotics
maybe twice a day

for several weeks,

and the moment you stop taking them,
you are not protected anymore.

But this is completely different
with a vaccination.

Most of the time,
it's enough to be injected once,

and then you're protected
for years to come.

There's no need to retake any medication;

there's no need to stuff
yourself with chemicals;

and you are still protected.

And the best thing is
that you are protected

no matter how often and when
you meet the dangerous bacterium.

And this amazing type of therapy

is only possible because we understand
what the immune system sees as dangerous,

because we know how to talk
to the immune system.

And lastly, your immune system
is also able to fight cancer.

It is also able to tell
that cancer cells look kind of weird,

that they are behaving strangely,

and is able to destroy them.

But sometimes this doesn't work.

Sometimes, these cancer cells

show basically stop signs
to your immune system.

They have learned
to talk to your immune system,

and they are trying
to trick it into believing

that they are not harmful.

And there are new types of therapies

that are currently being
developed and used

where we can destroy these stop signals,

where we can prevent the cancer cells
from talking to the immune system.

Then the immune system stays active
and destroys these cancer cells.

This therapy was
so revolutionary and so amazing

that the two researchers,
James Allison and Tasuku Honjo,

who have pioneered this field,

are going to receive
the Nobel Prize of Medicine

for this finding in two days.

So, you see, you have a great friend
in your immune system.

It can protect you from infections,

and it can help you fight cancer.

It can keep you safe
in this dangerous world.

And, sometimes, you just need
to talk it out of doing stupid stuff.

Thank you for listening.

(Applause)