OK. So I'm Claudette Gardel. And I am in the instructor of this
course. And I've been asked to do the second immunology lecture
because Professor Jacks is out of town.
So he talked to you on Friday. And he introduced the topic of
immunology. And he talked about the cells that one finds in the blood.
And these are the cells that are important for immunology.
They're responsible for the immune response. And he mentioned,
I believe he mentioned mast cells and macrophages and neutrophils and
plasma cells and B cells and T cells. And those are really the main
players of immunology. He also, no, no,
no. He also talked to you about the incredible diversity,
incredible, tremendous repertoire of antibodies that we have that
recognize variable, based on their variable regions they
can recognize a whole slew of antigens. OK?
And this is like a graphic depiction of an antibody.
This is a hetero-dimer, excuse me, tetramer. And this
diversity is a result of gene rearrangement in the variable region
of the antibody chains. And so you heard VDJ recombination.
So this is at the level of DNA recombination.
Similar to the gene rearrangement that occurs in B cells that results
in the diversity of antibodies, T cells also have rearrangement for
their variable region of their T cell receptors.
So we have a population of B cells and T cells that can recognize a
wide array of foreign antigens. OK. So this is immunology. This
is a topic that makes grown scientists run away.
And partly it is because there are so many terms and so much jargon and
it just seems so confusing to get it all straight. And it is.
There is a lot of jargon. So my goal in this lecture is to
try and make you understand conceptually what's going on.
OK? And I don't have handouts, but I promise I will put this on,
now, this isn't very helpful. But I will put this PowerPoint presentation
on the Web. And I have like tried to elucidate
the main concepts of immunology, which is so cool. It is like such a
cool topic. OK? So we're going to get through this.
OK. So what is immunology? It's how we fight infections.
And what causes infections? Pathogens. So let's have a look
and see what we're up against. This is what we're fighting. OK?
There are parasites and funguses,
fungi and bacteria and viruses. And they cause a whole slew of diseases.
You've heard of some of them, right? Smallpox we've heard of.
Influenza. We're going to study AIDS. We talked about polio a
little bit. We had cholera perhaps. And tetanus we talked about. And
what must every pathogen do to cause disease? They must enter you.
They want to live on you. They want to grow on you.
You are their food source. So they want to enter you. They
want to evade the immune system, which we're about to learn about.
They want to colonize and multiply and grow. And then they want to
spread to other hosts. That's all they want. Whether you
get hurt in the process they don't care. They can cause disease three
different ways. Pathogens have basically three main
strategies to cause disease. They can cause disease from an
extracellular point of view. And so here I've drawn some,
could you keep it down? Some epithelial cells.
These little spots here are nuclei. The pink represents damage. So
these pathogens can cause damage without being in close proximity to
the cell. This is usually the result of secreting a toxin.
And this occurs with tetanus, anthrax, gangrene. Other pathogens
have to be right up close to the cell surface to cause disease.
And this is true of the positive agent of cholera.
So they get up close and then they can cause damage.
And then there are others that are intracellular.
They actually get within the cell. And this is true of many bacterial
pathogens like chlamydia and the causative agents of tuberculosis.
And it's true of every single virus. OK. So we have developed
strategies to deal with this. And this strategy goes under the
main umbrella called the immune response. And the immune response
can be divided into two main parts, innate or nonspecific and/or acquire
adaptive and specific. OK. So this slide is actually my
summary slide. And it's going to blow you away a
little bit, but by the end of the talk you're going to understand it.
OK? So we're going to go through it really quickly,
you're going to like glaze over, and then we're going to go through
it. Oops. What happened? Tom? OK. Oh, that was good.
OK. So the innate. The innate response is composed of
things that we have all the time, natural barriers to the disease.
They're always present, it's a quick response, and it
doesn't result in anything long-lived. The acquired or
adaptive response takes longer. And it's divided into two kinds,
humoral and/or the other kind is cell-mediated or sometimes it's
called cellular and sometimes it's called cell-based.
This is why immunology is so confusing. Professor Jacks used the
word cell-based. And the main players of these,
they're going to be shown here. So humoral has macrophages,
helper T cells and B cells. The main player of the cell-base is
killer T cells. This is the pathway that they work.
You're going to learn about this in detail. Lysosome breaks up the
antigen into epitopes. It's presented on MHC-2 molecules.
In the case of cell-based it's a proteasome that breaks it up into
epitopes presented on MHC-1 molecules. And it's presented to
the helper T cell by way of its receptor which is associated with
CD4 or to the killer T cell which has a T cell receptor with an
accessory protein called CD8. The end result of the humoral
response, antibodies and memory B cells.
The end result of the cell-based response, memory T cells.
That's it. OK. So that's what you're going to know by the end of
the lecture. Here's the immune response. Excuse me.
Here's the innate. We're going to discuss the innate.
This is like an exploded diagram of a human sort of.
Now, I talked about pathogens and I talked about bacteria being
pathogens, but not all bacteria are pathogens. In fact,
we are colonized by bacteria. We are colonized by microbes.
In fact, they outnumber us. There are ten to the thirteen cells that
we have and there are ten to the fourteen bacteria.
They live on your skin. They live in our large intestine.
And this is a good thing, OK, because they're commensals and they
take up space to prevent real professional pathogens from honing
in on that space. So commensals are beneficial.
Plus we have this thing called skin.
Skin is a good barrier. It prevents us from looking like a
piece of meat. You know, it's tough.
It's thick. It's salty. It has a low pH. It's not exactly
37 degrees. It's a little bit cooler. Pathogens like to be at 37
degrees. It has fatty acids which is sort of anti-microbial.
Skin is good, yet some pathogens have evolved systems to get through
the skin. For instance, malaria gets in on a mosquito bite.
Yersinia pestis, the causative agent of bubonic plague which gets
in on a flee bite. OK. So some can get through the
skin. And then, of course, there are cuts.
The eye is mostly sterile due to lysozyme which is an enzyme that
breaks down bacterial cell walls. Your respiratory tract is
surprisingly sterile considering there are 500 to 1,
00 microbes per cubic meter of air. And as you're sitting here at rest
in 10-250 breathing in about six liters a minute,
that translates to about 10, 00 microbes a day. And why is this?
But I just told you that your respiratory tract is relatively
sterile. And that's because it's lined with mucus which traps the
microbes. And the cells along the respiratory tract have these little
cilia that look like little hair-like projectiles.
And they're beating up, constantly beating up the microbes.
And they get to the back of your throat and you swallow them.
OK? So you swallow them. And then the stomach, a sterile environment
because of the low pH. There are some microbes that can
live in the stomach and they cause ulcers. Small intestine.
Is that sterile or not? Nobody knows. It's very sterile.
It's a hostile environment. It's full of bile. If you can live
there, like vibrio cholerae, you'll be causing disease. The
large intestine. Is that sterile?
No. No. There are so many bacteria in the large intestine that
per gram of feces there's ten to the eleventh bacteria.
That's a one with 11 zeros after it. So it's a lot of bacteria.
And this is a good thing. E. coli secretes little vitamin K for
us and there are commensals. The bladder should be sterile.
The kidneys should be sterile. And the flushing action of urine is
constantly pushing down microbes that might be wanting to infect us.
OK. Within the blood there are also some innate components.
One of them is the complement system. The complement system is a
series of serum proteins that can recognize nonspecifically many
different bacterial pathogens. And they come, and it's an
enzymatic cascade, and they land on the surface of the
bacteria. And then they can either recruit other members of the immune
system or they can actually physically drill a hole in the
bacteria and then kill it like a little oil rig.
And then there are macrophages which I like to abbreviate this way,
macrophage. Macrophages are white blood cells that engulf,
they swallow, they phagocitize. Phago means to eat. Macro means a
lot. They eat a lot, and they eat nonspecifically.
They just swallow and take things away nonspecifically.
There are also interferons, a component of the innate response.
And that's interesting in that when a cell is infected with a virus
sometimes it will secrete. And it knows it's infected.
Sometimes it knows it's infected, and sometimes it has the ability to
secrete interferon. And there are other cells that have
receptors for interferon. And when it's through a signal
transduction mediated pathway they go into an anti-virus state and they
stop making protein and they start cutting away RNAs.
And so, actually, some of the bad feelings that we have when we have
flu is not really the flu virus. It's the result of interferons
being globally secreted in our body and our cells sort of
shutting down. OK. So here's the inflammatory response.
OK? And here we have a splinter. This is a piece of wood coming in
and look. Oh, look, it's coated with little
bacteria. OK? And, actually,
this experiment was done by Mesnekoff many,
many years ago where he took a splinter and he put it in a starfish
leg. Leg? You know, one of those little projectiles of
the starfish. And he looked. And he saw these cells trying to
engulf, actually trying to engulf the wood. And that turned out to be
the macrophage. OK? So he was actually the first
person who discovered the macrophage. So here we see the splinter
penetrating the dermis. And these cells here are called
mast cells. And they're full of vesicles that secrete histamines.
And the histamines cause the blood vessel that's underlying to become
more permeable such that the macrophages and neutrophils,
phagocytes can come to the area and swallow the bacteria.
So this is histamine, these are the macrophages that are
coming and swallowing. And also you can see these little
red dots are complement. Those are the serum proteins that
will come and land nonspecifically on bacteria and lyse them.
And the macrophage will also secrete something we
call cytokines. Cytokines are signaling molecules
that immune cells use. And there is a whole array of
cytokines and they have a whole different variety of affects.
Some cytokines have global affects upon us. They cause us to have
fever and not feel too well. OK. So after the infection you'll
notice the macrophage is swallowing a dead, infected cell.
They clean up. And then these cells with grow and
will be repaired. So this is the inflammatory response.
The hallmark is redness and swelling and heat.
So now let's discuss the acquired response. The acquired takes longer.
There was the humoral cell-mediated. The end result of the humoral
response are antibodies and memory B cells. The end response of
cell-mediated are killer T cells. We're going to talk about the
humoral response right now. And I'm going to give you an
example of a disease. This is vibrio cholerae.
It's a bacterium that causes cholera. There are some places in
the world where some people get cholera. And this person is
suffering. And the doctor has squeezed her skin,
and you can still see that the skin is upright because she is severely
dehydrated. The disease is marked by severe diarrhea that can lead to
death within hours. And they measure --
What they do to treat cholera is they measure the amount of diarrhea
that happens, and that is the exact amount that they replace in fluids.
The lifecycle of the bacterium is shown here. You ingest contaminated
food or water. The bacteria get through the low pH
of the stomach. They swim through the mucus gel
overlying the small intestine epithelial cells at which point they
adhere. And they start to elaborate cholera toxin and other factors that
allow them to colonize and multiply.
It's the action of cholera toxin which causes the severe diarrhea,
and it releases the vibrios into the environment and the cycle continues.
And some of you had in your signal transduction the action of cholera
toxin where it like turns on the alpha protein in the intestinal cell
causing high levels of cyclic AMP which results in chloride ions and
salt followed by water going into the lumen of the small intestine.
A person can die in as little as eight hours due to the action of the
toxin, and yet it's absolutely treatable with oral hydration.
And yet still 50,000 people die each year because it can take up to
40 liters of liquids to restore hydration. And sometimes it takes
place in areas where there's not water or for some reason small
babies cannot take in the water. Without treatment 70% will die.
With treatment less than 1% will die.
Now, there are some places in the world where cholera is endemic.
People get it and they get treated with oral rehydration.
And once you get it you don't get it again. You will have developed
long-lived immunity to cholera. And this long-lived immunity is a
result of the humoral response. So the next slide will show you the
two key members, actually three key members of the
humoral response dealing with a pathogen.
So here we have a macrophage, here we have a B cell. And look,
this little red dot could be a pathogen, it could be an antigen,
and it's about to be engulfed by the macrophage and it's about to be
recognized on the surface, it's about to be recognized by the
variable region of the antibody which is on the surface of this B
cell. This is the B cell. This is macrophage. OK.
So the macrophage swallows it and it goes into an endosome.
It endocytosis it or phagocytosis. It could be a phagosome or an
endosome it's called. The B cell does exactly the same
thing. It brings it in on the antibody. And so it's also in an
endosome or phagosome. And see this little circle here?
That's a lysosome. Do you remember lysosome? We had them early.
This is not lysozyme which is the enzyme that's in the tears that
break down cell walls. No. This is an organelle that is
found in cells, and it's full of degradative enzymes,
proteases, nucleases, lipases. And it just fuses with the
phagosome and chews it up into little itty bitty pieces.
And these little itty bitty pieces are loaded onto these molecules
called MHC class II molecules. And they display little eight or
nine amino acid snippets of what was just chewed up.
The only two cells in the body that make MHC-2 molecules are the
macrophages and the B cells. And who are they displaying it to?
Well, there's this third cell right here. It's the helper T cell.
And the helper T cell recognizes the MHC-2 class molecule in
conjunction with the epitope by virtue of its T cell receptor.
OK. And here are some helper T cells.
Here's either a macrophage or a B cell. This sort of looks like a B
cell. It's an antigen presenting cell of which there are only two
kinds, B cells and macrophages, and they have MHC class II. OK.
Here's another way of looking at it, pathogen engulf.
There's the phagosome or endosome. It looks like the lysosome is
already fused. It's broken up into little
fragments. Peptide fragments are called epitopes.
They're loaded onto MCH class II molecules.
Presented to the helper T cell. And now, look, here's the T cell
receptor. It has an accessory protein. The helper T cell
receptor's accessory protein is called CD4.
OK. So, now, remember the helper T
cell is going to bind to the macrophage? And it's going to --
Only if it recognizes the epitope in conjunction with MHC-2.
And should that happen the macrophage sends out some cytokines,
special cytokines that causes the helper T cell to also send out
cytokines to itself and causes it to clonally expand.
OK? So many more of these helper T cells are around.
So here we go. It's found the macrophage.
It becomes activated. It becomes in an activated state.
It clonally expands but it still remains in its sort of activated
state. And should it encounter a B cell that has swallowed the exact
same antigen or pathogen and is displaying the exact same epitope
then it causes the B cell to do something through the action of
cytokines. So here it's finding the B cell. It has the exact
same epitope. And it sends these cytokines and it
causes the B cell to clonally expand into memory B cells and also to
differentiate into plasma B cells that are now secreting the antibody
that originally recognized the surface of the bacterium or the
antigen. And now these are now being secreted into the blood or
wherever they are. OK. Here it is again,
helper T cell recognizes the B cell, sends a signal, clonal expansion.
The ones where the antibodies remain on the surface are called memory
cells. Now they're in greater abundance. Some of them
differentiate into these cells that have lots of endoplasmic reticulum
because they're synthesizing a secreted protein.
Now it's secreted and it's called antibody. So we've got all these
secreted antibodies and all these memory T cells, excuse me, B cells.
And this is the reason why the secondary response is greater.
OK? So the first time you encounter a pathogen or an antigen
it takes a while and it's not as great the magnitude of antibodies.
But the second time, because we have all those extra memory cells
around, it's much quicker and it's also a greater magnitude.
Now, if some of you were observing that there are these things called
IgM and IgG. Well, this refers to different classes of
antibodies. And there are different classes. IgM are the ones that are
sort of on the surface of the B cells. They're sort of still
tethered at some point. And then as they become plasma
cells they actually have secreted antibodies. And there are different
classes depending upon what fluids the antibodies will be found in.
For instance, IgG is the predominant antibody
found in the blood. IgA is found in some mucouses and
tears and mother's milk. So babies don't have any immune
system, but if they're nursed they get the IgA from their mother.
And, actually, it goes into their small intestine and just goes right
across into their bloodstream. So it actually helps them because
it takes the babies a while to develop antibody-making systems.
IgE is an antibody that has been implicated in allergic responses.
Do you remember the mast cells that have those ready pockets of
histamine ready to like secrete out and cause like a ray of affects?
Well, they also have receptors for IgE. And so some of us have
allergies, right? And when we have allergies we
develop IgE to ragweed or cat dander.
And as a result, if we're exposed to this antigen we
can have this reaction involving IgE in mast cells resulting in histamine
release. And if it's very bad then it can actually result in
anaphylactic shock. OK. So antibodies,
you know, we have a whole production of antibodies made.
But how do they actually fight disease? What do they do?
So we've got them floating in our blood? How do they rid ourselves of
the infection? Well, they do it three ways.
OK. Remember vibrio cholerae? It wants to get to the intestinal
epithelium to cause disease. Here's a bacterium here. Here are
antibodies that are specific to the surface of vibrio cholerae,
this bacterium here. It is coated with this furriness of antibodies.
Can it touch the tissue? No it cannot. It is sterically
hindered from getting to its surface. And this would be true of a toxin,
too, of a toxin, a protein toxin. A toxin is coated with antibodies.
It cannot get to a receptor and cause ill effects.
OK. So now we've got these antigens and bacteria and they're
coated with antibodies. Opsonization. This is derived from
a Greek word which means seasoning on food like salt and pepper.
So here's a pathogen. It's coated with antibodies.
In comes a macrophage and swallows it up. Now, the macrophage would
devour this thing anyway without the antibodies. But it might be slower.
It might be a little pokey. When you have --
It's like seasoning on food. When you have antibodies it's going
to do it voraciously. And why is that? It's because the
variable region binds to the bacterium or the pathogen or the
antigen. What's sticking out is the constant region of the antibody.
No matter what's on the variable region the constant region is the
same. So the macrophages have receptors that recognize this
constant region and they zip it up and they swallow it.
Likewise antibody triggers the complement system,
so although the complement system might come in slowly,
when it sees antibodies bound to a bacterium it comes in and it does
its little oil drill thing instantly. OK. So that's how antibodies
prevent disease. Here's a picture of the macrophage
with its receptors. This end of the molecule of the
antibody is called FC. So the receptor is called the FC
receptor. And it just coats it and brings it in and ingests it.
OK. So we've got antibodies as a result of the humoral response.
Would they be affective in preventing a toxin from binding to a
surface if we had antibodies against that toxin? You bet.
It's very good for pathogens that cause extracellular disease
away from the cell. It's very good for toxins,
extremely good. What about preventing cholera again?
Can it prevent a pathogen from binding to a surface,
an adherent bacterium? Yes. We just showed you it did.
Sterical hindrance. But what about the case of viruses or other things
that are intracellular, that cause disease from within,
would antibodies be effective there? Only if they were caught before they
got in. But once they're in they're protected from macrophages.
They're protected from antibodies. They're in a nice, warm,
nutrient-rich environment. They're looking pretty good.
And many professional pathogens have opted for this tact.
So what we've done is we've developed the other wing of the
immune system called cell-mediated to deal with intracellular
pathogens. And these are the stars of the
cell-mediated or cell-based or cellular system.
And they are called killer T cells. And they are the coolest cell in
your body. They're like the Terminator, you know,
Arnold Schwarzenegger, the Terminator. And so they go
around and they like will protect us. So let's show you this. OK.
This thing that looks like a suitcase is my drawing of let's say
an epithelial cell that has been like sandblasted away.
OK? One side of it is sandblasted away so we can look in.
Oh, look, there's its nucleus and there's its endoplasmic reticulum.
And what are these things on the surface of the cell?
Well, it's called MHC class I molecule and it's presenting and
epitope of eight to nine amino acids.
All nucleated cells in the body. Every cell in your body that has a
nucleus is presenting MHC class I molecules on their surface,
presenting epitopes on MHC class I.
And where did these epitopes come from? They come from proteins that
are found in the cytoplasm. At some point routinely proteins
are channeled through this organelle called a proteasome.
They get threaded through and they get broken up into eight or nine
amino acid snippets, and they get loaded onto MHC class I
molecules in their final stages of being transported to the membrane.
And who are they presenting, these MHC class I molecules to?
They're presenting them to killer T cells by way of the
T cell receptor. Now, although most of the epitopes
that are presented on these MHC class I molecules are derived from
your own proteins, host proteins. Any killer T cell
that could have recognized a host protein, in conjunction with the
MHC-1 molecule, has been eliminated early in
development. Early in development if there is
recognition. That killer T cell has been targeted for apoptosis and dies.
And this is true with B cells, too. So if they have an antibody on
their surface that can recognize a self protein they are eliminated.
And this is called clonal deletion. So what is left in our blood are
only killer T cells that can recognize foreign epitopes in
conjunction with the MHC class I molecule.
And so if the cell is infected, and it is because I drew in these
chlamydia, and if some of these proteins are chlamydia proteins and
they are being presented on these MHC class I molecules,
and the right killer T cell with the receptor that comes by and
recognizes it, if recognition occurs two things
happen. OK. Here's the killer T cell. Here's the MHC-1 with the
chlamydia epitope or a pathogenic epitope.
A foreign epitope sitting right there. The killer T cell says oh,
my God. We have a cell that's infected. Maybe there are other
cells that are infected. I've got to make more of me.
And it clonally expands to make more of itself with the exact same T
cell receptor that's going to recognize this epitope.
It also punches a whole in the cell using perforin.
It secretes this thing called perforin.
It punches a hole in the cell. And if that's not good enough,
it also secretes something called granzyme B which causes this cell to
undergo apoptosis. So it like double kills it.
OK? And here's like another picture of it.
So here's the virus. The proteins are loaded onto MHC
class I molecules. The killer T cell recognizes it by
way of its T cell receptor. And its successor protein is CD8.
OK. Here's the infected cell.
Here is the killer T cell. There's the CD8. This is perforin which is
going to puncture a hole in the infected cell.
It figures it better kill this cell now and save the rest of the body.
It decides to sacrifice the infected cell. And here's granzyme that
causes apoptosis. And this cell then ends up looking
like this with holes punched in it, cytoplasm streaming away and starts
to undergo apoptosis.
And it makes more of itself. So you end up with an army of
memory killer T cells that are going to recognize this exact pathogenic
epitope. Here's a killer T cell. Here's an infected cell. And
here's a movie.
Remember I said Terminator, right? OK. There's the T cell.
There's the cytoplasm streaming away. And look it. It just keeps going.
It doesn't stop. It just keeps going. Punching away.
Wasn't that awesome? Let's do it again. OK.
That is so cool.
Yup. OK. And they're on our side, you know. This is the army we have
going in our blood. It's just awesome. It's just
awesome. OK.
OK. So this is the T cell receptor. This is found in both helper T
cells and killer T cells. Notice it has a variable region.
Early in its development the T cell precursor actually has
both CD4 and CD8. And it's immature at this point.
It doesn't know what it is yet. It has both. And then as it develops
it has only one left. So if it remains with the CD4 it is
a helper T cell. If it has a CD8 in its final
differentiated state it is a killer T cell.
And it's this accessory protein that, actually that's it,
that's what causes it. And so if we look up close and
personal at an MHC receptor, this could be MHC-1 or MHC-2.
This accessory protein could be CD4, CD8. So if it's MHC-1 the accessory
protein is CD8. If it's MHC-2 the accessory protein
that fits MHC class II would be CD4.
So now I'm hoping that this will
become a little bit more clear for you. So the innate response had
lysozyme, the mucus, ciliary ladder, skin and complement,
and macrophages and mast cells. It doesn't last very long.
And it's really not completely effective in, you know.
It wouldn't really work that alone. We'd need the acquired and adaptive
response which takes a couple of weeks the first time.
And so the humoral response and the cell-mediated or cellular or
cell-based response. The humoral response has the
macrophage that first engulfs the antigen and the B cell that
recognizes the antigen through its specific tethered on its surface
antibodies. Both of them engulf it, break it down and present to the
helper T cell. The cell-based response involves
killer T cells. So inside the macrophage and the B
cell a lysosome comes over, it fuses with the endosome, breaks
it into epitopes which get loaded on MHC class II molecules.
Inside every nucleated cell in our body we have a proteasome that is
breaking anything that's found in the cytoplasm onto epitopes.
And if the cell is infected those are going to get broken into
epitopes and loaded on MHC-1 molecule to be hunted down by killer
T cells. This is recognized by a T cell receptor with an accessory
protein CD4. This one's recognized by a T cell receptor with an
accessory protein that's CD8. See, it's not so hard, right?
It seems a little bit wordy, but conceptually --
So the T cell causes the blood, the B cell to clonally expand. Some
of them become plasma cells which secrete antibodies.
Some of them become long-lived memory B cells.
The killer T cell, recognizing an infected cell,
will secrete perforin to punch holes in it, granzyme B to kill
it through apoptosis. And it also creates lines of memory
killer T cells such that the next time we see the same pathogen,
if any, we're ready. OK. So, now, if we didn't have the mechanism to
make antibodies or T cell receptors, what if we only had the innate
response? And there are people who don't have the acquired
or adaptive response. Oh, excuse me.
These are other terms. And they're called the ìbubble boyî.
Have you heard of the bubble boy? They have to live inside a bubble,
basically a plastic shell that's completely sterile.
They either don't have B or T cells or they don't have any antibody or T
cell variation. And so the innate response is not
quite good enough. And so, on the other hand,
sometimes you can have an overactive immune response.
For instance, you could have killer T cells or even antibodies that
recognize or start to recognize host proteins. And this happens.
And the end result of this is autoimmune disease.
So here's an example of an autoimmune disease that's caused by
killer T cells that have now started to recognize beta cells in the
pancreas as being infected and they kill them. And the beta cells in
the pancreas are cells that respond to levels of glucose in your blood.
So you have like a candy bar, you eat a meal, there are high levels of
glucose in your blood. The beta cells secrete insulin so
that your entire body, the cells in your body will make
glucose receptors to take that glucose out of the blood and utilize
it. So if you don't have beta cells because they've been killed by the
killer T cells you don't make insulin and you get diabetes.
Let's see. What other autoimmune diseases? Lupus is an
autoimmune disease. Sometimes you can have antibodies
that recognize the myelin sheath, the cells that make up the myelin
sheath, and then those cells are destroyed. And that results in
multiple sclerosis. So these are autoimmune diseases,
when the immune system goes wild or goes bad. OK.
So I've just sort of built up the immune system as being really great
and wonderful. But some of you might have questions
and some of you are thinking, well, you know, gee, I've had the
flu twice. My roommate has had strep throat a couple of times.
What gives? What's with this secondary response,
this acquired response? Well, pathogens, some pathogens,
it's an ongoing war, have developed strategies to overcome our immune
system. And that's why we use antibiotics to kill them sometimes.
OK? And they're nasty, you know, and they grow fast and
they mutate. And they can develop ways of getting around our immune
system. For instance, this is a picture of Bacillus
anthracis. It has developed this enormous polysaccharide capsule that
absolutely prevents it from being phagocytosed by macrophages.
Without the capsule it is absolutely harmless.
It absolutely requires the capsule to cause disease, as
well as a toxin. That's the only thing it needs,
a toxin that is on a plasmid and in a capsule. Or,
let's say we develop antibodies to neisseria gonorrhea,
or we develop antibodies to malaria. What they do, these pathogens, some
of them very clever ones, is they say OK, antibodies are
recognizing things on my surface. I know. I'll just change my surface.
And they'll change their surface. They'll put up a different protein
for phase variation or they'll mutate. And the antibodies are so
specific that they cannot recognize this mutated protein,
and it's like we're getting it again for the first time.
And this actually happens with cholera.
So in places where it's endemic, people get it once, they develop
long-term resistance, and then 20 to 40 years suddenly
adults start getting cholera again. Actually, I'm not even sure it
happens that quickly. The last one happened in the late
1990s where it just started wiping out adults. And so whole clinics
had to be developed in town squares for oral rehydration.
And what had happened was that the bacterium, the vibrio cholerae
bacterium changed one sugar residue on its surface.
Just one little sugar changes. A fructose turned into a mannose,
right? And that was it, because that was what the antibody
recognized. So now new antibodies have to be made to that one so
people will get it twice. There are some bacteria that make
proteases that are designed to cut our antibodies in half.
So horrible. So they just go in there and they just secrete these
proteases, and the antibodies have just like degraded.
Let's see. Some pathogens can survive phagocytosis.
They send out little messages that prevent the lysosome from coming
over, and they live in the phagosome.
And, oh, I'm going to be leaving you on a sad note,
ha? But, all right, do we have any questions?
Do we have any questions?
No? Perfectly clear? OK. You can go.