ADAM MARTIN: And
today, we're going
to talk about immunity, which
is important, especially
at this time of the year.
So immunity is the
resistance to disease
based on a prior exposure.
Based on prior exposure.
And of course, this is the
principle behind vaccination.
So humans have
been sort of using
the properties of
the immune system
to prevent themselves from
getting disease for centuries.
One of the first very
clear examples of this
is back in the 18th century with
the English physician, Edward
Jenner, and Edward Jenner found
out or came to the realization
that farm hands on
farms, specifically
milk maids, that were exposed
to a variant of smallpox
from cows, which is
known as cow pox,
could become immune to smallpox.
So cow pox is a less
severe form of the disease.
And what Jenner did
was to take pustules
from individuals who
had the cow pox disease
and inject them into
an eight-year-old boy,
and then infect that
boy with smallpox
to show that the boy was
immune to smallpox after having
received the cow pox material.
And so this is the first
example of the vaccine.
And because the vaccine was
derived from basically someone
with cow pox, the
word vaccine is
from the Latin root
of vaca, which is cow,
so that's where the word
vaccine comes from, OK?
So today, we're going to
talk about the systems
that our bodies have
to fight disease
and there are several
different all levels
of the immune system.
So I'm going to talk
about two of them.
So I'll talk about two
levels of immunity.
The first I want to
mention is the one
that we're all just
like born with,
which is known as
innate immunity.
[SNEEZING]
[SNEEZING]
Bless you.
So innate immunity,
as the name implies,
is something that we are
born with, so this is inborn.
It also doesn't have a delay
in when it's activated, right?
So if you have an
infection, this
is sort of the first
line of defense, right?
There is an immediate response,
and that's the innate immune
system, so this is immediate.
Here, I'll put this down here.
It's immediate.
So one example is of an
innate immune response.
This is not in the
body but ex vivo,
but here you see a
human neutrophil,
and neutrophils are part of
our innate immune system.
And neutrophils hunt and
kill bacteria, right?
You see that neutrophil
chasing after that bacterium,
and it's going for it.
It's really trying to get
it, but that bacteria really
wants to get away, but got it!
OK, great.
So these neutrophils are part
of the innate immune system.
It's inborn, it's immediate.
And in addition, the response
of the innate immune system
doesn't really
change if you've been
exposed to an infectious
agent prior to the--
OK, so this does not change.
I'm using the Greek
delta for change.
Does not change
with prior exposure.
OK, so it's sort of like
a constant surveillance
mechanism in your body that will
go after foreign agents, OK?
Now, this is very different
from the next level
of immunity, which is
known as adaptive immunity.
And as the name adaptive
immunity implies,
this is a type of
immunity that does change.
It adapts, OK?
And this type of
immunity is acquired,
so it's also known
as acquired immunity,
but it's acquired with exposure
to a foreign agent, OK?
So this involves a change in
immunity, this one does not,
but the innate immune
response is immediate,
whereas adaptive
immunity takes time.
There's a delay, so
this is also delayed.
It's also highly specific, OK?
So it's highly specific
to the foreign agents
that you are infected with.
The innate immune
system is less specific.
It'll recognize, like,
things like bacteria,
but it won't be able to
necessarily distinguish
between different
types of bacteria.
So this is more specific than
the innate immune system.
This is why every year,
you have to get a flu shot,
because the flu virus
is constantly changing.
And our immune
system is so specific
that unless we get
a new vaccination,
our bodies will not be
able to recognize it, OK?
So this is-- so now I'm going
to break down adaptive immunity
into two branches.
One is known as
humoral immunity,
and humoral immunity is
basically protein-mediated,
and there are
proteins that mediate
this are called antibodies.
These antibodies are proteins,
and it's called humoral
because the antibodies
can be secreted
into the fluids or humors of
our body, which is basically
the blood, OK?
So there is humoral immunity.
The other type of
adaptive immunity
is cell mediated,
and one thing I
want to point out that the types
of cells that make an antibody
are known as B cells.
What the B stands for
isn't really important,
but one thing that's
helpful is that these cells
mature in the bone marrow, and
B stands for bone marrow, OK?
So you can always remember
where they mature.
Now cell-mediated
immunity, in contrast,
involves a different type
of cell called a T cell,
and the T of T cell
stands for thymus
because these cells
mature in the thymus.
And I just want to point out
where these cells come from.
So we talked about adult
stem cells earlier,
and in this case, these T
and B lymphocytes over here
are derived from a
multipotent hematopoietic stem
cell, which generates
a whole bunch
of different types of cells.
Many of them are involved in
the innate immune response,
but this common lymphoid
progenitor over here
gives rise to D--
T lymphocytes and B
lymphocytes, which are
involved in adaptive immunity.
OK, so it's not important
that you remember where--
what all these cells come
from or what they, like,
what the tree is, but
that these cells arise
from a common progenitor cell.
OK, so both of these branches
of the adaptive immune system
have what are known
as antigen receptors.
I'll abbreviate antigen, AG.
So they have antigen
receptors, meaning
that they have
things on them that
recognize specific antigens,
and antigens are basically
things that result in
an immune response.
They could be proteins.
Antigens are substances that
activate the immune system.
That's just immune system, OK?
Another abbreviation
that I'll use
is when I refer to an antibody,
I'm going to abbreviate it, AB.
All right, so we have these two
branches of the immune system,
and they each have the
type of antigen receptor,
so now I want to go through
what these different types
of antigen receptors
look like, OK?
And I'm going to start with the
B-cell antigen receptor, also
known as the antibody, also
known as an immunoglobulin.
OK, so another-- these
are all synonymous,
but you will see them
in different contexts.
Immunoglobulin is
abbreviated IG.
And what the antibody
looks like structurally,
it looks like
this, and I'll just
draw it out for you down here.
So I'm drawing a
lipid bilayer that
represents the plasma membrane.
The outside of the
cell is going to be up,
so that's the exoplasm up here.
The inside down here
is the cytoplasm.
And this would be a B cell,
then, we're talking about here.
I'm going to draw just a segment
of the B cell plasma membrane.
And the B-- the antibody can
have a transmembrane domain
that spans the plasma membrane,
and then there are domains--
and what I'm drawing here is
a circle, is an IG domain,
so this is going to
equal an IG domain.
It's just a type of protein
fold that is modular, OK?
So you can see up on
my diagram here, right?
You see these like here there
are these two green segments
labeled V and C. Each of
those is a single IG domain.
OK, it's just a
modular fold that
is separate from the
other part of the protein.
OK, so here we have along--
this is one
polypeptide chain that
has a transmembrane domain, and
it is inserted into the plasma
membrane.
The N-terminus is here, the
C-terminus is down here,
and each antibody protein has
two of these long peptides.
And because they're the
longest part of the molecule,
they're known as heavy chains,
so these are the heavy chains.
And each antibody protein
is composed of two
identical heavy chains, OK?
So these are identical.
And then also there's
another component,
which is present up here, and
this is a shorter polypeptide.
And because it's
shorter and smaller,
it's known as the light chain.
OK, that's the light chain.
OK, so that's more or less
what an antibody looks like.
The part of this
antigen receptor that
recognizes the antigen
are the tips right here,
so this is where
the antigen binds,
and it can bind on either
this side or this side.
This molecule is
laterally symmetric.
One side is identical
to the other, OK?
Now, the T-cell receptor
looks different,
and the T cell receptor
has fewer names.
It's just called the T-cell
receptor, or the TCR,
for short.
And the T-cell receptor is
structurally very different,
so now I'm drawing here
a T-cell plasma membrane.
Here's the plasma membrane.
The exoplasm, again, is up.
The cytoplasm is down
below this plasma membrane.
And the T-cell receptor
has two chains.
One is called alpha
and the other is beta,
and it has fewer
immunoglobulin repeats,
so that you can see you just
have this sort of smaller
system here, where you have
an alpha and a beta chain.
And in this case,
this region here
recognizes the antigen, OK?
So basically the T-cell
receptor, or the tip of it,
interacts with the antigen.
Now, the B-cell receptor,
or the antibody,
has different forms, so let's
talk about the different forms.
And these are shown up
on my slide above, right?
So you see over here,
here is an antibody that
has a transmembrane domain
and is anchored in the plasma
membrane, but there's
another form that
lacks that transmembrane
domain, and instead
of being an integral
membrane protein,
is instead secreted
into the blood, OK?
So the forms of
the B cell receptor
are both a membrane-bound
form, which is initially
how this antibody is
presented, but later on, it
can be secreted, and
this often changes
when there is an infection, OK?
So once you have a virus
or bacteria in your system,
then you get the B cells
sort of pumping out
the secreted form
of the antibody
in order to fight
the infection, OK?
In contrast, for
the T-cell receptor.
For the T-cell receptor,
there's only one form, which
is the membrane-bound form, OK?
So for T-cell receptors,
it's membrane only.
OK, another thing that differs
between these antigen centers
receptors is the types of
antigens that are recognized.
So antibodies can recognize all
sorts of different molecules,
OK?
They're very
promiscuous, but they--
and a given antibody
is not promiscuous.
A given antibody will recognize
a very specific structure,
but the possibility
for antibodies
is that they can
recognize small molecules.
They can recognize proteins,
they can recognize DNA,
they can recognize
carbohydrates,
you get the idea, right?
They really can recognize a
whole range of different types
of molecules.
In contrast, the T-cell
receptor is more restricted
in that T-cell receptors will
recognize peptides or short
sequences of amino acids.
So it recognizes peptides,
and these peptides
are presented to the T
cell on a type of molecule
presented by the MHC complex.
There are two classes,
1 and 2, and we're
going to talk about this in
detail in Friday's lecture.
So I just want to point
out the difference
in the types of antigens
that can be recognized here,
and we'll talk about exactly
what that means on Friday.
OK, so now we have to talk
about the amazing properties
of the immune system.
The first is how specific
it is, its specificity,
and I think this is a really
amazing property, the ability
to really discriminate between
very closely related molecules,
right?
And this is essential for
immunity to work well.
You want to recognize things
that our foreign agents that
have like invaded your system.
You don't want to be recognizing
proteins and structures that
are natively present
in your body,
because if your immune
system did that, you'd
have an autoimmune disease,
so this specificity
is really crucial for the
function of the immune system.
So now I want to talk how is it
that the immune system achieves
such high levels of
specificity, and the way
I want to illustrate
this is I want
to bring this down quickly.
So if we consider the
structure of the antibody,
these different domains
are different in that--
in how variable they are,
so some are variable.
So this domain here
for the heavy chain
is the variable domain of the
heavy chain, which I'll just
abbreviate VH, and then these
other immunoglobulin domains
are constant, meaning they
don't have a lot of variation
in sequence.
Like the heavy chain,
there is a variable domain
for the light chain,
which I'll abbreviate VL,
and then there is a constant
domain for the light chain, OK?
And so what I want
to do now is consider
what the sequence variation
is here on this antibody
is the same over here.
This is the same
thing over here.
You have a variable
domain for the heavy chain
and a variable domain
for the light chain.
So let's consider the amino
acid sequence of the antibody
molecule specifically at that
variable part of the protein.
So let's say we could
take individual antibodies
and define their sequence
from end to C-terminus.
That would be from tip
towards the end here.
So if we take a number
of different antibodies
and align their
amino acid sequence--
so what I am--
I'm not writing out an
amino acid sequence,
but I'm just illustrating
like a particular type
of computational
experiment you could do.
So these would be aligned
amino acid sequences
where each of these represents
a different antibody, let's say,
heavy chain polypeptide that's
produced from a different B
cell, OK?
So each of these is a different
antibody from a unique B cell.
And then we just consider
the residue number
and how much each
amino acid residue
varies along this sequence.
So if we were to align antibody
gene stretches like this
and look at how much
variation there is,
you'd get a graph that
looks like this, OK?
So the y-axis is the
amount of variation
and the x-axis here
is the residue number
along this polypeptide sequence.
And what you see, probably
even without the color here,
is that there are these
three regions where there's
a lot of variation
in the sequence
of different antibodies, OK?
So here you see the blue segment
here has a lot of variation,
the yellow segment has
a lot of variation,
and the reds segment here has
possibly the most variation.
And what these are known as
are hypervariable regions,
meaning that they exhibit
a lot of variation.
Another name for
them is that they
are complementarity-determining
regions.
Complementarity.
Complementarity-determining.
Determining regions,
or CDRs, and there are
three of them, 1, 2, and 3, OK?
So there are regions in
this antibody molecule
which are much more
variable than others, OK?
So what are these regions?
Well, this is a sort of
crystal structure of the--
of an antibody, and you
can see how the antigen is
bound at the end.
That would be this
end of the molecule
or this end of the molecule.
And here you see
a ribbon diagram
of the structure
of the antibody,
and the complementary
complementarity
determining regions
are the regions here
that contact the antigen.
And what they are
are basically here's
an IG fold, this whole thing,
and there are these three loops
that extend out of the
end of this molecule,
and you can think of them
as three fingers, OK?
Then these fingers are able to
reach out and sort of grab on
to like a foreign particle
and/or any particle
and stick to it, OK?
So these are the
variable regions,
and they have differences
in amino acids--
in amino acid sequence,
and even very small
differences in the
amino acid sequence
at this particular
part of the antibody
can have a huge effect
on whether or not
they're able to stick
to something, right?
You can imagine if
I lost my thumb,
then right now, I'm not
able to sort of stick
to that anymore, OK?
So small differences
in amino acid sequence
result in large changes in
the affinity of this antibody
for an antigen. And antibodies
have different sequences,
meaning that they're able to
bind to specific substances
differently.
So if an antibody has
one set of sequence,
it might recognize
one structure.
If it has another
sequence, it might
recognize another structure.
So just by changing
the sequence at
these
complementarity-determining
regions has a huge influence
on what these proteins will
bind to, OK?
Now, each B cell expresses
a unique antibody
and just one unique antibody.
So each B cell in our body
expresses one and only
one antibody protein,
and that antibody protein
has a unique sequence
at the CDR region,
and this one antibody has unique
specificity for an antigen, OK?
So here you can
see in my diagram,
I have a whole bunch
of B cells here.
They all express a
different antibody,
and you can see that the way
you could get more of a given
antibody is to clonally
expand one of these cells,
and all of the cells that result
from that colonial expansion
will express the
exact same antibody.
And when you have a clonal
population of a cell
that all has the same antibody,
that's known as monoclonal, OK?
So each B cell will have a
B-cell receptor or an antibody
with unique specificity.
So now the question
becomes, OK, so I told you
how you get specificity,
but in order
to have a functioning
immune system,
you need to have lots
of different cells
that each express a
different cell receptor,
so there needs to be a
way to generate diversity.
And the answer to how
we generate diversity
has an MIT connection.
The research wasn't done
at MIT, but the person
who discovered the
mechanism is now at MIT.
This research was performed
by Susumu Tonegawa,
and Professor
Tonegawa, for his work
on how this diversity
is generated,
was awarded the Nobel
Prize in medicine in 1987.
OK, so Professor Tonegawa
did this research elsewhere,
but now he is a faculty
member here at MIT.
All right, so diversity.
The problem of diversity, right?
We have millions of B cells
that have a unique antibody.
OK, so one solution
to this problem
would be we have a million
different antibody genes,
and each B cell clone sort
of expresses one of them
OK how many genes do we have?
Anyone know, roughly, on
the order of magnitude?
Do we have a million?
What's that?
AUDIENCE: 30,000?
ADAM MARTIN: Exactly.
Yeah, so Mr. George
has suggested--
Miles, I believe.
Yeah, OK, good.
Miles suggested 30,000, which
is the good upper limit, right?
So having a million
antibody genes
sounds a little
bit unfeasible, OK?
And so it's basically
unfeasible for us
to express as many
antibody genes
or have as many antibody
genes as we have antibodies.
We just don't have enough
real estate in our genome, OK?
But there's another
solution to generate
the diversity,
which is essentially
a form of shuffling.
So we have a single heavy
chain gene for antibodies,
and we have two genes
for the light chain,
but these genes are composed
of multiple gene segments.
There are multiple
gene segments.
Specifically, the
segments that make up--
that generate this
variable domain is composed
of multiple gene segments,
and these gene-shaped segments
are shuffled during the
development of the B cell
to give rise to
different proteins.
OK, so these gene segments
are shuffled to generate
this diversity.
OK, so now I'm showing
you on the top here,
this is the human immunoglobulin
heavy chain locus here.
You can see it's pretty big.
There are lots of components.
I want you to focus on this.
So there is-- you see in orange,
there's this variable gene
segment, and there are 45
variable gene segments here.
There's this
diversity, or D segment
here, which there are
23 of, and then there
are six of these
joining or J segments.
OK, so these are all
distinct parts of the gene.
They're all distinct
parts of the exon
that encodes this variable
region of the antibody, OK?
So you have multiple V,
D, and J gene segments.
And in order to generate
a functional antibody,
one V has to be brought
together with one D, which
has to be brought together with
one J for that heavy chain, OK?
So you have multiple
V-D gene segments,
and they have to
be brought together
to form a functional antibody.
OK, that's illustrated
right here.
So here you see this
is the light chain.
For the light chain, there are
only V and J gene segments.
V For the heavy chain,
there there's V, D, and J.
And so most of the
cells in our body
and the cells of our
germline, at the very earliest
stages of development,
all have this arrangement,
where you have
everything still intact.
But during lymphocytes
development,
specifically in lymphocytes,
there is a recombination event
that brings together V
and J segments or V, D,
and J segments, OK?
So this is mediated
by recombination
at the heavy and light chain
genes for that antibody, OK?
And so this is very different
from the recombination we
talked about earlier in the
semester, where recombination
is happening during meiosis and
the formation of the gametes,
right?
In that case,
recombination is happening
between homologous chromosomes.
Here we're not talking
about recombination between
homologous chromosomes.
We're talking
about recombination
that brings together
and deletes segments
along a single chromosome
to bring these V and J
segments together, OK?
So this is sort of
a intra-chromosomal
recombination, which deletes
the intervening sequences
and brings these gene segments
together to form a functional
antibody protein.
So this process is known
as V(D)J recombination,
and this is lymphocyte specific.
OK, and that's because during
the development of B and T
cells, there is an induction
of recombinases that
mediate this recombination.
So in this case, there
is recombination,
which is mediated by
recombination-activating genes
1 and 2, called RAG1 and 2, OK?
So there are these are
lymphocyte-specific
recombinases which mediate
this rearrangement, which
bring together a unique V, D,
and J segments together, OK?
So the diversity
comes from the fact
that each of these V, D and
J segments, each V segment--
you could-- this also applies
to D segments and also J
segments--
has a unique sequence.
So it encodes for a unique
amino acid sequence,
meaning that if
you bring together
different combinations
of Vs, Ds, and Js,
you get a distinct protein, OK?
Now even if you had all of the
combinations of V, Ds, and Js,
you still don't
have the diversity
that we see in the human body.
So there is another process that
further generates diversity,
which is the fact that when
these segments are getting
shuffled, it's imprecise in
that nucleotides can be inserted
or deleted as these
segments are joined,
which generates greater
amino acid diversity,
and this is called--
it's called junctional
imprecision.
So this recombination
is not precise,
but it leads to the
insertion or deletion
of nucleotides of nucleotides.
And if there's a
multiple of 3 nucleotides
either inserted or deleted, then
you get a functional antibody.
Why is it that it has
to be a multiple of 3?
Jeremy?
AUDIENCE: Otherwise, you end
up with a frameshift mutation.
ADAM MARTIN: Exactly.
Right?
This is and the--
this is on the more sort
of like on the N-terminus
side of the gene, right?
So if you inserted one
nucleotide between V and J,
then the downstream portion of
the gene, the downstream part
of the open reading frame
would be out of frame
and wouldn't generate
a functional protein.
OK, so it has to
be a multiple of 3.
Yeah, Georgia?
AUDIENCE: How is functional
precision lymphocyte-specific?
Or is it not?
ADAM MARTIN: It's
just the RAG1 and RAG2
are turned on specifically in
the lymphocytes as they mature.
AUDIENCE: And that also affects
the insertion, deletion?
ADAM MARTIN: Well, if you
don't have recombination,
you can't get junctional
precision, right?
So the junctional imprecision--
or junctional imprecision.
The junctional imprecision
is a consequence
of the recombination
process itself, right?
So if you're not
having recombination,
you're not having any
junctional imprecision
because you're not
generating a junction.
OK, now there's one more
thing that's important here,
which is something
that happens not
as a consequence of this
recombination process
but as a consequence of
activating the T cell
response, which is that in
addition to these variations,
there's also something
known as somatic mutation.
So there's an elevated
mutation rate at the IG locus
that further increases the
diversity of the amino acid
sequence at these variable
regions of the antibody, OK?
Another way this
is referred to is
because it can increase the
affinity of the antibody
for a antigen, it's also
known as affinity maturation,
so these are synonymous.
Maturation.
Maturation.
OK, so-- and this
depends on the T
cell, the cell-mediated
branch of adapted immunity,
so this is T-cell mediated.
So one other aspect
of this process
that I want to talk about
is until this recombination
happens, the immunoglobulin
gene is not expressed,
so it's this
recombination that leads
to the expression of the--
either the heavy chain
or the light chain gene, OK?
And that's because the
enhancer is sort of downstream
in the gene, and by deleting
the intervening sequence here,
you bring the promoter
in range of the enhancer,
and now this gene
is expressed, OK?
But remember you have two
copies of each of these genes.
You have a parental copy
and a maternal copy,
and another feature
of this system
is that there is what is
known as allelic exclusion.
So the system is such that
a B cell expresses only one
antibody, and so if you had
both alleles expressing,
that wouldn't be the case, OK?
So allelic exclusion makes it
that if you get a recombination
event that leads to a
functional antibody for one
of your sort of inherited
copies of the gene, one
of your alleles, it suppresses
recombination on the other one,
OK?
So you will only get one of
these genes, one heavy chain
and one light chain,
expressed per B cell.
OK, so only one gene expressed
so that each B cell only
has one antibody.
OK, I just wanted to
point out, finally,
that these junctions
between V-D and J segments
fall right in this
CDR-3 region, so they're
responsible for the high
level of variability
at the CDR or
hypervariable 3 region.
OK, and because of
the allelic exclusion,
each B cell expresses
only one antibody, OK?
So all of the antibody
proteins expressed by that cell
will be exactly the same.
OK, so now the last property
of the immune system we
need to talk about is memory.
And so the immune
system needs to be
able to recall past infectious
agents that it's experienced,
and so it needs--
I guess we're kind
of personifying here,
but it needs some
sort of memory, right?
It needs the ability
to recall this, OK?
And this is the principle
behind vaccination, right?
The way vaccines
work is to put in one
of these attenuated or
inactivated foreign agents,
such that your body is
able to remember that
later on when you
get the real deal,
and it's able to
fight it off, OK?
So the body has to
be able to remember.
And several ways in which
this manifests itself,
if we compare a primary
infection, the first time
you've seen an infectious agent,
versus a secondary infection,
they have very
different responses
from the standpoint of the
adaptive immune system, OK?
So if we consider the lag before
your adaptive immune system
really takes off,
the primary response
takes about five to 10
days, so it's a bit delayed,
whereas the secondary response
can be one to three days, OK?
So it's faster.
It's able to react faster when
you see an infectious agent
the second time.
If we also just consider the
magnitude of the response
by considering how much
antibody, the antibody
concentration that's like
put into your system,
then the primary
response is smaller
and the magnitude of the
secondary response is larger.
So you basically-- your body's
able to produce more antibody
against an infectious agent
the second time it sees it.
Not only is the antibody
amount better the second time,
but actually the
antibodies themselves
are better antibodies, OK?
And we can show that by thinking
about antibody affinity, which
is how tightly the antibody
recognizes the antigen,
and I'll give you
numbers that represent
the dissociation constant for
an antibody to a given antigen.
So the lower that number
is, the tighter the binding.
So for the primary infection,
the antibody affinity
is weaker on the order of 10 to
the negative 7th molar in terms
of KD, and this
secondary infection
generates antibodies that are
functionally quite better.
They bind much tighter.
It can be less than 10 to the
negative 11th molar, which
is sub-nanomolar.
Right?
That's a really
tight interaction
between two molecules.
So the antibodies,
you get more of them,
and they're better
antibodies, OK?
So what makes this memorable
is that when-- what lasts
in your body from the first time
you see the agent to the next
is there's a type of B cell
known as a memory B cell,
and this memory B cell will
express a given antibody,
and that antibody will be
specific to the substance
you saw previously.
And because recombination
is-- this recombination
is irreversible,
then that B cell
is going to remember that
antibody because it's still
encoded in the genome.
So the memory results from
V(D)J recombination being
irreversible and the fact
that these memory B cells stay
in your body, even if the
antigen is not present,
so these also stay in the body.
OK, so effective vaccines
generate these types
of cells, these memory B cells.
OK, that's important if you
want an effective vaccine,
that you have these B cells
that retain information
about the past infection.
All right, so what exactly
is it that the antibodies do?
So I'll talk about effector
functions of antibodies.
So antibodies can bind
to a foreign substance
and interfere with the
normal function, right?
If you have a bacteria
and maybe the antibody
binds to some part
of the bacteria
to interfere with that
bacteria getting into the cell,
and this type of effect is
known as neutralization.
If you had an antibody
that bound to something
like a bacteria,
you could also have
it recruit phagocytic cells
to internalize that bacteria,
and so you could also
induce phagocytosis.
In addition, antibodies, when
bound to a foreign substance,
if that foreign
substance is a cell,
then it could recruit a
killing cell to kill that cell,
so there's also a killing
aspect to this, OK?
So what's in this diagram
here is a type of cell
known as a natural killer cell
that is killing its target
cell, and so you
can kind of think
of this cell as
the Terminator, OK?
So right, if the natural killer
cell recognizes this target
here, then it's
hasta la vista, baby,
and that cell is dead, OK?
I just want to point out one
thing that I mentioned before,
which is that antibodies
can be leveraged to generate
treatments for certain
types of diseases.
And we talked about a drug
called Herceptin-- or not
a drug but a-- it's
an antibody, but it's
a treatment for HER2
positive breast cancer,
so this is used to treat
HER2-positive breast cancer.
And it's really been a nice
success story in the cancer
field because what this--
what Herceptin is-- it was
derived from a mouse antibody,
so this is a mouse
monoclonal antibody
that recognizes this
HER2 growth factor
receptor, which
is over expressed
on 30% of human breast cancers.
And what Herceptin is is that
researchers took this mouse
antibody and engineered
a human antibody
to have the mouse sequence at
its complementarity-determining
regions, such that you
have a human antibody that
won't be sort of removed
by the human immune system
but will recognize HER2 and
recruit human immune cells
to HER2 positive cells,
possibly killing those cells
or binding to HER2 and somehow
neutralizing the activity
of HER2 on these cancer cells.
So antibodies can be very
useful for therapeutics, as well
as being useful in our own
bodies to mediate immunity.
OK, we'll talk about
T cells on Friday.
Remember to bring your projects.
