TEST 1.3 - Immunology
Sun, 2/6 11:54AM • 46:08
Professor
Alright guys, so in this in the second lecture we're gonna, we're going to focus on the organs of the
immune system, again on different cell types, going to, to more depth. Shortly, the term hematopoiesis,
even though it refers to a large extent how you make blood, it's just so including, I mean, the term by
itself. haematopoiesis refers how you make blood. And when you say how you make blood, people
would typically think of red blood cells. But even more, I guess even more important in terms of the
immune system is how do you make immune cells. Now, we said everything starts in, in your bone
marrow. So if this is a bone what's inside your bone is worthless, responsible for generating all the
nuances. There are stem cells, which we refer to them as hematopoietic stem cells, they tend to be CD
34 Positive. And these are the cells responsible for giving rise to all the progenitors that ultimately give
rise to your immune cells. They are extremely capable of proliferating. And we know that even if you
take a tiny amount of stem cells, they're capable of re establishing hematopoietic hematopoiesis. Now,
as far as you're concerned, two types of progenitor cells which are relevant to the immune system, what
we refer to as the lymphoid Progenitor, and the myeloid steps, we're going to see later on when we talk
about the lymphoid Progenitor, we're primarily talking about progenitor cells that give rise to
lymphocytes and InfoSight related cells and to myeloid cells, which includes macrophages, platelets,
red blood cells, dendritic cells, so, the the two major divisions when it comes to making immune cells is
what we refer to as the lymphoid age and the myeloid lineage, okay, so, it all begins with a CD 34
positive, but then it kind of bifurcates into lymphoid or my, these are the key things, lymphoid or
myeloid. Now, you take a petri dish, or you take any flask for that matter, and you put some bone
marrow. And then you give the flask proteins growth factors. And after a while, what you're seeing is
that, oh, it really works. And you start getting nice colonies. We refer to these as columns. When you
give them these growth factors, which growth factors this is this is what I'm referring to. This is what's
referred to as a colony. trend and decrease a little bit the size. So this is what's referred to as the
column. Again, you take bone marrow mixed with all kinds of stem cells, accessory cells, and you give
them these proteins, and all of a sudden, they start proliferating. Now, this is used in real life when
someone is anemic. And they don't make enough clock. In that case, you would give them EPO, you
are the VP or before or if appointed, that would allow them to make more red blood cells. So this is for
making red blood cells. When it comes to the immune system. People especially elderly people who
people have been subjected to chemotherapy, their leukocyte levels go down. Things like neutropenia
and when they go down, what do you think is, is imminent? When your leukocyte levels go down?
Infection? Yeah, that's the number one thing you have to worry about. Are you going to get an
infection? So the technology is there, they inject people they give them an intravenous injection of
growth factors. And depending on which cell type they're missing, we'll quickly they start making more
of those cells that you look. So, in general, we have these four types of Colony stimulating factors. You
could also give people IL-2, which is not technically economy, colony stimulating factor, if you give
people IL-2, they start making a lot of T cells. It is one of the available tools. When you're trying to fight
cancer, the idea is by making more T cells you will be able to fight the cancer. Okay. But that's as far as
you're concerned, is just be aware that the bone marrow when subjected to these growth factors, it will
respond and it will stop making more of those cells. That's, that's the ad. So here's your typical culture,
bone marrow. Now, the stromal cells, their accessory cells includes things ranging from fat cells,
fibroblasts, you need them. You need them there, they're helping you get all those immune cells. And
this is your typical colon. When I was a graduate student, we used to take bone marrow and generate a
lot of dendritic cells. So the way to do that you would take a GM CSF for you and I'm sorry, GM CSF
and aisle four. And that if you use bone marrow, he will give you a lot of dendritic cells, DCS dendritic
cells, so that's one of our ways of manipulating the bone marrow to give us a lot of dendritic cells,
because we were interested in dendritic cells. So the bone marrow when is subjected to this colony
stimulating factor is all of a sudden we start making a particular cell type, sometimes it makes a number
of cells. Okay, and again, you when there are patients, we have issues with hematopoiesis you give
them this the only drawback these are known to be causing cancer. In the US, you're trying to
reestablish normal levels of particular cell type, but you're also increasing the chances of inducing
cancer okay, because that's cancer is about over proliferation. Now, this recipe I like this picture,
because it shows you how the system works. So, remember, I was telling you we have a hematopoietic
stem cell a good marker for that I said the CD 34 positive meaning those stem cells express this
marker, they don't have to that is not about markering kind of gives you so, which are the two pathways
you could do you could either do a myeloid Well, you could do the lymphoid So, what are some cell
types you you end up with following the myeloid we have the dendritic cells but do pay attention, you
we do have something Dudek cells which come from the lymphoid lineage plasmacytoid dendritic cells
for example, they're known to come from the lymphoid lineage going back to the myeloid platelets you
know, platelets are the things that help you avoid hemorrhage, but they also cause clotting, which
continue nobody thinks of platelets is you know, the most exciting part until they kill you until you get a
Gnostic thought and you know, you don't talk about So, we have monocytes macrophages, this you
know, basically monocyte these one is in the cloud or kind of granulocytes basal fields, you you see no
fields and of course, we have red blood cells. Now, look at the lymphoid lineage, we have the NK cells,
we have the two types of T cells, they could either be th or they could be set a toxic we have the B cells
right then for this you could always add the plasma cell which is this the only difference between a
typical B cell and a plasma cell is that this one just keeps making a lot of Antibody Okay, so you get the
idea right off the origin of each immune cell now, he quit Important? Yes yes, yes, for example
plasmacytoid dendritic cells, they, they're really the first line of defense as soon as you get a viral
infection, they would make a lot of interference, interferon alpha and beta via a typical myeloid dendritic
cell is more involved in in Antigen presentation, I would make a lot of Cytokines, yes, but they do have
different functions. If you are a dendritic cell who the lymphoid lineage, you won't be exactly the same
thing as a modular. Now, cell death. This is an extremely useful phenomena. And I know you don't think
of death as something useful. But when it comes to the immune system, it's critical that you have death,
right? If you don't you end up with leukemia. Example good example. You go to war, right? We like to
do that right? Every, every 10 years, it's good for the military industrial complex. What do you think
happens to all those equipment and all those soldiers, because when there is a war, we pick them up,
right? A lot of them they end up in Arizona, they put them like people fighting for, for really cheap. The
soldiers you bring back home and you try to rehabilitate them, you know, maybe they go to college,
they find a job, right? But you cannot sustain having a humungous military for an extended period of
time, it's just too expensive. The same exact thing happens to your immune system, you cannot sustain
when you have an infection to keep the same number of immune cells, he just chew up so much
energy between the nervous system and the immune system. They consume energy like there is no
tomorrow. And part of the reason you feel horrible when you have an infection is because the immune
system pretty much sucks all the energy between the two the nervous system and the immune system.
So there's no way you could survive for for a year having this massive immune system on the attack is
just going to take you down. Okay, so what do you do, you have to decommission them, you have to
die, they die, and they die without making a big deal about it. That's that's the idea. So that's what cell
death is about. Just to give you an example, our neutrophils, they only live for three days. We make
billions of neutrophils, and they only last for three days. So these authorly death, which is a very good
thing to happen. We refer to this a book toss. And these are the hallmarks of apoptosis. You see a
reduction in volume, chromatin, condensation, DNA degradation, the macrophages come in, and they
eat you for lunch. And perhaps the most important thing is that there is no inflammation. This thing
happens on a daily basis. On the other hand, if you get necrosis, you do get a lot of inflammation.
What's a good example of necrosis, you know, I hit you with a hammer, damage yourself, they die. Of
course, the immune system schwob, you get edema, there is pain, there is inflammation, there is
accumulation of cells, which are supposed to fix the damage, or when you get an infection, and the
pathogen kills a lot of your cells, because pathogens, they make toxin, again, you want to get a lot of
inflammation, that there are fundamental differences between apoptosis and Muckross acrosses will
keep inflammation and I'm not saying you know, in a crisis is that's how you take care of things, you're
going to have these massive inflammation and you're going to fix things, but you cannot have an
extended period of necrosis, eventually, you're going to go down. While apoptosis is something which
happens on a daily basis. It's very normal. So he has a picture, if you like, which describes the crosses
and apoptosis. In this case, we have an across it, you see a lot of inflammation. I mean, to be fair, the
macrophages do show up to clean up the mess. Just like in apoptosis, you need the people to show up
to clean up the mess, but you're bringing a lot of other soldiers, because you're really trying to figure out
who's causing the mess. In this case, you're assuming that there is no mess, this is everyday, everyday
phenomenon. And you see how nicely that kind of self destructs These guys come and pick it up. And
there is no inflammation Okay, any questions as a rule of thumb when something birds and things from
the cytosol end up outside, you think that's going to be an inflammatory situation or it's going to be a
non inflammatory situation. Climate when you're spilling your guts out, as in the case, when you visit,
bursting of a member, and bursting of a membrane can happen just from playing injury, or it can happen
from being infected with the flu virus hijacks of your machinery makes so much video and you end up
exploding that would cause inflammation. So, these are pictures, electron microscopy pictures, which
they show you this blabbing phenomenon turning into into either bubbles if you like. So, this is a normal
cell healthy cell. And this is an apoptosis. Now what decides when something is going to undergo
apoptosis, or it's going to continue living, I always like to put a seesaw. And you have people pushing
on one side and you have people pushing on the other side. As long as you are in a balanced level,
you're not going to die. So if this is the part which you're going to undergo apoptosis. So what are some
genes which inhibit apoptosis. BCL two is, is a very good gene, which is known to inhibit apoptosis.
This was discovered, believe it or not, in a B cell lymphoma, that's what the initials are. In a lymphoma,
the cells don't die. Right? No, they supposed to die, you're supposed to generate some B cells and
they're supposed to die unless you have an infection, which is only a short period of time. So in this
case, with the lymphoma, they discovered this gene, obviously, he was he was wasn't allowing the cells
to die dcl tissue. So the cost basis on the other hand, they do exactly the opposite, they will promote
apoptosis. caspases are like proteases, they will self digest your proteins and such. So the balance
between these pro apoptotic and anti apoptotic genes is what determines whether a cell is going to
leave or it's going to become able to talk. Okay. So he has a nice example of a B cell missiles, your job
is to make antibodies. So they make antibodies, B cells. And they're also second in command in terms
of Antigen presentation, right? Which Antigen presentation is your presenting peptides? Now, look at
this situation where the B cell presented an Antigen maybe was is part of a bacteria, which the B cell
encountered, and he's presenting it to a T helper cell. And the T helper cell would typically make a lot of
Cytokines. If it's if it's recognizing something which is dangerous. So, you would make a lot of
Cytokines. Now, the BCL two levels in general, for a B cell and normal B cell are low, which means it's a
severe destined to die, unless you have Cytokines, which bind the cytokine receptors. And that gives
you a boost not to die. So it's a CPAP cell is wired to die unless there are Cytokines around. If there are
Cytokines around it means it's needed. So in that case, is going to go this way become a plasma cell or
become a memory B cell, but eventually is going to die and die. Because the Cytokines won't be
around forever. Okay, once you cleanse things, you don't produce a salad. If no Cytokines, let's say this
was something boring that was presented and no Cytokines were secreted. Remember, he has very
BCL two very low BCL two levels, so it's going to go this way. He said, You know what, I'm not really
needed. I don't see a lot of Cytokines being released when I'm presenting these things. So I'm not really
needed. So I'm going to die. Don't worry, I will make some new ones in the bone marrow, some new B
cells would follow. So this shows you you as abyssal you get to expand and you get to proliferate, only
when there is a need. If there is no need, you know, you're presenting your things and they're very
boring. They're primarily your own proteins. No need to expand, just die. We'll get some humans. So
the analogy is I said, when there is a war, yes, you need an expanded military, from when it's everyday
life, daily life, where your proteins are being presented to the immune system, your own proteins, you're
going to have a short life, short, boring life. Okay. Now, how can we detect apoptosis? So we become
we're pretty good at this, we, if you look at the membrane of a cell remember the phospholipid bilayer.
So it turns out that there's there's a phosphor liquid called Phosphatidyl serine, which normally is found
on the inside, on the cytosolic side, so it's facing this way. And there is an enzyme called Flip ace which
ensures that the majority of Phosphatidyl serine is on the inside. Flip is relies on ATP. As soil which is
very low in energy, is likely gonna 100 co equal cost. So when you are when you have low levels of
ATP, your flip is doesn't work as good the activity of the flip is so you start seeing Phosphatidylserine on
the exterior. And when for certain cities in the exterior is acting as a as a flag for an immune cell to
show up and each kind of interesting, right? He show you the importance of energy, you don't have
enough energy, you will become able to talk or you could ask me how do you know if hospitality scene
is actually being expressed outside. We do have a protein called the Nexen five which has a high
affinity for for satiety signals. But the only way it's going to bind is a fatality series is on the outside, it's
on the inside it doesn't know. So you can take a short title city, maybe you put the fluorochrome Maybe
it's a green fluorochrome You know, and all of a sudden you're seeing green cells, it's an indication that
the cells are apoptosis. Let's talk about cells of the immune system. We said lymphoid cells, the B cells,
the T cells, there is the natural killer cells, which the if you look at the B cells and the T cells. So let's
say this is a T cell, this is a visa. And then you look at an M case. In the case of a T cell, they have
what's referred to as a TCR. They have a T cell receptor. That's how they recognize peptide. In the
case of a B cell, they have BCR receptors, which are they look more like antibodies, and that's what
allows them to recognize antigens. In the case of NK cells, they are blind. We cannot recognize
patterns. So logically you say wait a minute, how can they believe for itself when they really don't have
the capacity to recognize the pattern? It turns out they rely heavily on antibodies. So if this is another if
let's say this is a bacteria, he will be coded with antibodies Maybe one of your cells, the moment you
code it with Antibody, do you think it's a good sign or a bad sign? It's a bad sign. If if for whatever
reason antibodies are sticking to you, and quite a few of them, you are in trouble, it means we're going
to get rid of. So in this case, the NK cell has receptors, which recognize the tails of the Antibody, and it
will bind to them. And eventually, he would attack you, the NK cell would attack. So despite the fact that
is totally blind in terms of recognizing peptides, it's recognizing the fact that you're coding with Antibody.
In these cells, they play a critical role at the beginning of an immune response. They're not sure killers.
So that's why we call the mouse cells, because they're really not your classical inputs. So these cells,
they tend to be pretty small. If you look at T cells and B cells, they're really small, six micrometers in
diameter. And when you look at them, you isolate them from blood. You look at the nucleus, it occupies
a large part, a large part of the cytosol. That's what he does. So when they've never been in combat,
we refer to them as naive. They're naive, to think of them like rookies, the rookie sale, for them to see
combat, they have to, they have to go out to the lymph nodes. And they have to go out in sites where
there is pathogen attempting to penetrate. When they come out of the thymus, they're naive to want to
talk about the science. These are some nice pictures of lymphocytes. You see how prevalent the
nucleus is, in terms of the CyberSource pretty much occupies like 90% 80% of the of the entire cell.
When you see this type of thing, we refer to these as a plus cell, they tend to be bigger. If you start
seeing blast cells plus cells or like progenitors, if you're seeing them in your blood, do you think it's a
good thing or a bad thing? It's a bad thing. Actually, that's a sign of leukemia, or lymphoma issues. You
because they're supposed to be there in the bone marrow, primary issues, which should be in the bone,
which shouldn't be in your periphery, which you should be seeing in your periphery of finished B cells,
periphery I mean, in the cloud. And here's a plasma cell. It doesn't show very clear but here you see a
lot of rough endoplasmic reticulum. Why do you think you have such a pronounced in the plasma?
What's being made on rough endoplasmic reticulum? Why is your rock because there are ribosomes
right? Well the ribosomes do they make proteins? What type of proteins do plasma cells make?
Antibodies right? These guys they just keep pumping onto this. Okay, any questions how they're
present here with the flow cytometry looks like bioinformatics. You bioinformatics is basically utilizing all
the data you generate. Elyse has earned flow cytometry where the real thing you doing this is what you
do in the lab, you generate the data. Bioinformatics allows you when you have tons of data to
manipulate and come to a conclusion Are you comfortable with the input cells so which are the B cells
T cells now cells. Now, this is data coming out of the flow cytometer. And is essentially the way your
lights scatter light. The way your cells scatter light. This is where your lymphocytes are sitting. They're
relatively small, they don't have too much internal complexity. And very quickly, you could determine if
someone has an abnormal number of lymphocytes whether they have an infection or they have cancer,
just by taking a tiny amount of blood and passing it through a flow system. You could use antibodies in
pinpointing exactly what the percent of T cells is B cells monocytes. You name it using Flow cytometry,
but you have to use antibodies. And guess what we know what's a typical range of, of immune cells
someone should have under normal conditions. So with flow cytometry, you could very quickly
determine okay, I'm seeing about 30% lymphocytes, typical, the patient is running fever, I'm seeing an
elevation of monocytes monocytes, you typically find here, it's always a good idea to start throwing in
antibodies. So you can pinpoint exactly each cell population. So flow cytometry is something new. He
started with When HIV started exploding in the 90s. And as you know, HIV destroys T helper cells. So
they wanted to see the levels quickly the levels of T helper cells, because the lower the T cells were at
the time, the less chances are, the less chances you have for surviving. Now of course, they have
drugs which fight the virus and it doesn't destroy your thesis. But this this thing turned out to be a
beautiful thing. But back then he was he was a company also clinical diagnostics in New Jersey, which
they were pretty big with flow cytometry. But then, Becton Dickinson took over. And now there's so
many companies will do flow cytometry why wire flow cytometry is useful because they can give you a
very fast analysis of someone's blood in terms of their immune system. And it's like looking at the
military status of someone, you know, what's going on, are they going in a war or they have a healthy
system. So, you quickly realize, oh, this person is under infection this person, you could also have the
possibility of this person having some type of leukemia. So, you and that, you could also assess here,
you could figure out or you have way too many lymphocytes, but they are all problematic, they're not
the finished product. So, this is classical information. Okay. So, flow cytometry is extremely useful in
assessing the immune system. Now, how do we identify cells, there is this thing called cluster of
differentiation, which proceeded for just about every imaginable immune cell we have markers. So,
unless T cells B cells, macrophages, dendritic cells, here they are, they would be expressing some
unique marker, which we know about and we gave you the number. CD won, you know, she before she
da, CD 14, CD 19. So for example, CD one CD is good for dendritic cells, CD four is good for T helper
cells. CDA is good for cytotoxic T lymphocytes. CD 14 is good for macrophages. monocytes. CD 19 is
good for business. So you get the idea, right? We have markers forever, yes, this is the way the body
recognizes. When cells talk to each other, they do pay attention to these markers. If I am a Cytotoxic T
cell lymphocyte and you're presenting the Antigen via MHC two, I won't be paying attention. As I said a
toxic lymphocyte I always want to see my Antigen in the context of MHC one. If I am a visa, and you
know they they pay attention, yes. And this this liberal receptors, then sometimes they have functions.
And guess what? here lately we started making antibodies to block these receptors and start changing
the behavior of the immune system. Checkpoint blockade. It's the hardest thing in cancer
immunotherapy, how to mess with the immune system to make it more aggressive to fight the cancer.
Things like TiVo your voice. This is this is how we tried to do it. And I think they're exaggerating a little
bit. Then we have things like the car technology where we engineer the T cell receptors, and we put
them back in the patient and they go fight the cancer. So yes, these receptors are critical recognition in
functional medicine. Obviously, there's a lot of CD markers over 300 and we have antibodies with The
moment you have an Antibody, if you put a fluorochrome on that Antibody, there's no way you could see
that the Antibody is stuck. It stuck to that cell. So you put the Antibody, the Antibody is going to bind to
what you're looking for. But how do you know it's bound, he just put the fluorochrome pass through the
machine, you know, the floor comes right? Something that fluoresces passing through the machine. If
you're seeing that the cell is green. That's a no brainer for the cell to be green, it means the Antibody is
bound to it, and is binding what I was looking for. He understand this concept. That's how do we know if
cells express certain markers. That's how we know which cell type they are. We just put antibodies, we
put antibodies, which are specific to things we're looking for. And then we put flow crumbs on those
antibodies, we hit them with a laser, and then they give you the light. And we basically making the
correlation that if I'm seeing reddish fluorescence, or the Antibody are used to variable sclerosis, is the
Antibody that recognizes CDA, or so I know I have CDA itself in that vial. So who does the recognition
the Antibody desert the Antibody is what allows you to, to find what you're looking for. But how do you
know if you recognize you rely on light on fluorescence coming off the Antibody which Antibody stock.
So at the end of the day, the machine says, Oh, I see green, I see red, I see orange. Oh, I see green
and orange in this by you know in advance that your antibodies have these fluorochromes. And you
know, in advance what these antibodies recognize. You could take a vial of blood and you could throw
in five, six different antibodies pass them through a machine and based on the color you're seeing from
the cell, you could quickly say okay, 20% lymphocytes, Houston percent monocytes 16%, B cells 5%
and cases. And not only that, you could say all your B cell is expressing a weird, they are all expressing
the same light chain. But they shouldn't because you're supposed to be diverse. And all of a sudden
you're saying wait a minute, you're telling me that the oil come out the same V cells what does that
mean? A certain type but if the only let's say the light chain the oryx plus Express lambda chain in that
case, you should be concerned because your immune system is only making one clone of B cells.
That's a very characteristic of of informers. Because you're supposed to make a variety of clones when
you have an infection you don't just make one flaw. So you see how quickly you could distinguish
between an infection and in some type of an anomaly. Cancers gentleman All right. Worst slide with a
definition of a worst slide. Throwing a table with 150 pieces of information. This qualifies as a worst life
but it kind of condenses everything. All the city markers that I've been telling you which you already
know some of them for example, take CD for that reminds me of a T helper cell right? Take CDA that
reminds me of a cytotoxic T lymphocyte. Ah How about this reminds me of an NK cell meet me talk
about these guys. System FC receptor FC gamma receptor number three. Now if you look at cells.
These receptors, what they do is they recognize the tail of an Antibody. So this is a gamma Antibody,
that's why this is an FC gamma receptor. So cells have receptors which recognize the tails of an
Antibody. So when I say tail, if this is the Antibody, this is the tail of the Antibody. On this side, this is
where the bind Antigen so a lot of cells express these FC receptors Okay, so FC receptors are being
expressed in a variety of systems. How do NK cells recognize Antigen, who said they're blind. They rely
on what they rely on antibodies, right? If you're seeing something, we just call them with an Antibody.
That's how they know I should eliminate this, especially if they combine it with lack of expression of
MHC, Sarah, not only your coding with Antibody, you're not expressing MHC, which means you're trying
to hide something. As a rule of thumb, your MHC shows what you have inside you. What you ate for
lunch, or what what's typically inside, if you stop, which is where it can happen if you downregulate
expression of MHC is like a house where you close all the curtains, so nobody can see you from
outside what you're doing. Where you could say I'm doing it for privacy. But maybe you're doing
something wrong. thing, something that you don't want the others to know about. So that's a typical
viral infection. If I'm the virus and infected this, would I want to let everybody know, here I infected this
cell, so the new cells can show up and kill me? Why would I do it right? I want to survive. So I just
infected you, I will slowly hijack your machinery so I can make more of me. But that wants some time. I
don't want everybody to I don't want to let everybody be aware that I just infected cells. So what they do
about the virus is a downregulate expression of MHC. Eventually, the immune system figures it out.
Because they remember the NK cells are looking, they're looking for, they're looking for antibodies,
which are stuck on your surface. So they want to figure out why or one way or another, you're going to
burst and you're gonna you could hide it temporarily, but inevitably, it's gonna happen. Have you ever
wondered why we have such a low tolerance for for anything different than our cells? Okay, what's the
big deal? I thought viruses, that's how they spread genetic information, right? We got some genetic
information. Everybody thinks we all started from viruses. But once you build the system, you become
very, very territorial. So I don't want you to stay out, you know, we're willing to tolerate them on the
surface for No, we're not willing to tolerate them inside any ideas. I'm sorry. We are vulnerable from the
point of view that if I come in, and I start introducing DNA, which is you know, my viral DNA, I start
throwing my DNA, in your own DNA. Remember that DNA is nicely organized to get the job done. So
that, basically, you're going to mess up someone's genetic information. And the whole system is going
to fall apart, there has to be separation. Once you build something, who is like you have to have a
computer, you're not going to just allow any software to come and be installed and mess up with your
operating system. You understand why the immune system is very picky. And it's so picky we we don't
even tolerate things from from the same species. Because the whole system would fall apart. The only
time we tolerate DNA from another even though from our own species is during conception. This is the
only and that is a very well designed system. Your mother and your father, they're going to end up
together and mixing up the DNA and you're going to start having a new life. And during that
development, the mother takes unusual steps to keep you on track. You know KVH situation where
even the news the immune system of the mother won't be able to, to interact with the baby's cells. So
the placenta ensures that why because the baby's 50% Father, forget about his 50% father, the
mother's immune system cannot tolerate the father's immune system. So you see how it works. That's
why I cannot give you my kid chances in this room, we're not compatible with each other. You give me
your kidney, I can assure you within a week or two I'm going to reject unless I am put on
immunosuppressants, and unless we find a kidney, which is closely related to my kidney, I'm gonna
reject. So that's, let's see, that's the ad to take a little break. Alright, let's take a look.