Transcribed by Leslie Afable 5/16/14

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Organ Systems Lecture 58 Lymphoid Organs II by Dr. McCutcheon

Slide 33 Lymph Node- Meeting For Periphery and Circulation
Dr. McCutcheon Alright, so yesterday we started with the lymph nodes so to
remind you, the lymph node is a what? Its encapsulated. Whats this? The afferent
lymphatic. Whats this? Pardon? Paracortex. Whats this? This is the cortex.
Medullary fold. Medullary sinus. Hilus. Ok good, oh, high endothelial venule. Good.

Slide 34 Untitled Slide

Dr. McCutcheon Ok, so looking at pictures, so here is the capsule. Although in the
cartoons, theres the schematics of organs when they show a SINUS it has NO cells in
it. Thats actually NOT TRUE. So what the sinus has are FEWER cells and they are
not resident. Alright? So they drift through the sinus in the process of going
somewhere else. So you have the capsule. Here is our not empty subcapsular sinus.
But these cells are all in the process of heading elsewhere. And here is our cortex.
Thats mostly B-cells. So if we come down here, again, so this is in the medulla and
this is a sinus but again its going to have cells in it. It just doesnt have permanent
full time cells in it, whereas the cords, the cells are going to be clustered in the cords.

Slide 35 Untitled Slide (Low Powered Magnification)
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Dr. McCutcheon So the dark blue areas are the mutter, mutter, mutter, mutter
loudly. CORTEX (C), thank you. And this, MEDULLA (M). Whats that? Germinal
center, good. This area right here, paracortex (P). Good.

Slide 36 Untitled

Dr. McCutcheon So, right here? Germinal center (GC). Medullary ..medullary cord
(MC), there we go. Medullary sinus. Paracortex (P), and then this whole area is
cortex (C). Is everyone starting to get a sense for how these relationships work?

Slide 37 Untitled
Germinal Center
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Dr. McCutcheon Now if you have a sinus, a space in the middle of an organ filled
with cells, you have to do something in order to make sure that you keep the space.
What the lymph organs do is they have RETICULAR CELLS and RETICULAR
FIBERS that hold these spaces open. So here we are looking at a reticular cell and
here we can see a reticular fiber coming off that cell. So these cells are lining the
sinuses in order to keep that space open. Then in/amongst we can see
LYMPHOCYTES. So the sinuses, the medullary sinuses have reticular cells with
reticular fibers. This is in contrast to the THYMUS where the reticular cells have the
tight desmosome junctions but there are NO FIBERS. So in the thymus, the
meshwork is ALL CELL. But you are not trying to keep a sinus open, you are just
trying to create a surface area for the thymocytes to sit on. In the lymph node, in the
medullary sinus, you are trying to keep a space open and you do that by having
reticular cells that have reticular fibers that give you a defined structure and thats
what makes a sinus a sinus. Otherwise it would just fill in with cells.

Slide 38 Untitled

Dr. McCutcheon In the germinal center, and one of the more annoying parts from
your point of view about immunology is that it is not a linear topic. You can start at a
place but there are always other things that have happened first so its sort of
circular. I teach it as linearly as possible but its not possible to teach it linearly
Reticular Cell


Reticular Fiber
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because its a circular subject. So, there will come a reason for this when we get
down to the B-cell part of the immunology part but in fact germinal centers are full
of MACROPHAGES. Alright? GERMINAL CENTERS ARE FULL OF MACROPHAGES.
So weve done a stain here for one of the enzymes in a macrophage and you can see
bits and pieces of macrophages in this particular plane and the reason for that will
become apparent when we get to the B-cell part of it but you need to have the
macrophages in the germinal center because there are lots and lots of apoptotic B-
cells. Macrophages eat apoptotic bits. Back in the days when what the only thing we
knew about something was what it looked it, the histologists named everything that
looked somewhat different in the hopes that at some point in time it would have
function. Thats not always true, but they named macrophages full of apoptotic B-
cells as TINGIBLE BODIES. Ok? There is no special rhyme or reason to those that I
know of but the histologists named it 50 years ago. So if you look in histology
textbooks there will be things called tingible bodies and thats a macrophage full of
apoptotic B-cell bits. But remembering that there are lots and lots of
macrophages in germinal centers is really important.

Slide 39 Untitled

Dr. McCutcheon OK so this thing labeled with a P is the paracortex. Here is a
germinal center (GC), and again back in the days when histologists named
everything that looked somewhat different, they said there was an area of the
germinal center called the MANTLE (Mn) and supposedly this has different cell
populations in it and it really doesnt, but if you look on older slides you see this
MANTLE ZONE of the GERMINAL CENTER. Germinal centers are usually NOT
ROUND, ok so youve got the cap, the mantle zone here, and the apex there. I dont
think theres a reason for that, its just the way the cells happen to cluster.

Slide 40 Untitled
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Dr. McCutcheon OK now I want everyone to stop and picture in your head a
CAPILLARY and what the endothelium of a capillary looks like. Can someone
describe it? Thin, good. Not porous. Thin and flat, yep. What kind of connections do
the cells in the endothelium have? DESMOSOMES, right. So you have this incredibly
thin, flat layer of cells. OK? This is a venule. Do you see any thin, flat cells lining for
the endothelium there? Yes, no? Got lots of nos, the nos have it. Instead, these are
actually the endothelial cells and instead of being thin and flat, they are ROUND and
PUFFY. Ok? Its a venule and youve got round, puffy or high cells. So what is this?
High endothelial venule. The point of these round and puffy cells is if you are a thin
and flat cell and you are mushed up against the next thin and flat cell next to you,
how is a lymphocyte going to get out? If you are a round and puffy cell and you have
big spaces between other round and puffy cells, how does a lymphocyte get out? Ok,
so the point of the high endothelial venule is you change the endothelium in the
lymph node so that there are spaces in between the cells and that lets the B and T
lymphocytes go out of and into the lymph node from the circulation. So the
endothelium of the high endothelial venule looks different than the
endothelium of everywhere else in the body because we want to have the
lymphocytes be able to crawl out.

Slide 41 Summary
Dr. McCutcheon So in summary, we have this encapsulated organ that has 2
separate sets of circulation, the afferent lymphatics drain the PERIPHERAL
TISSUES. The efferent lymphatics will then send mature or maturing cells off to the
site of infection. The other circulation is the high endothelial venule and that lets
what and what go where and where? B cell and T cell go to circulation to the lymph
node and back. The B cells go where? Primary follicles. The T cells go where? Where
are the primary follicles located? In the cortex. Then we also have the medulla and
in the event of an infection, this is where the maturing plasma cells are going to be
MATURING and they will be in which part? The cells? The 8 oclock people were
more awake than you. So the question is if you have an immune response and you
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have maturing B cells and they are in the medulla, what part of the medulla will they
be in? The sinuses in the medulla. The secondary follicles are part of the cortex. So
thats where the B-cells proliferate then as they start to mature they move into the
medullary sinuses. Then from there they will go into the medullary cords so they
can go out the efferent lymphatic. Please note, in addition to the lymphocytes, lymph
nodes are full of macrophages and they are full of dendritic cells. Alright? So lymph
nodes have macrophages, dendritic cells, B cells, and T cells. Any questions
about lymph nodes?

Slide 42 Lymph Nodes
Dr. McCutcheon OK, encapsulated, trabeculated, lobular, has follicles, has cords and
sinuses, has cortex and medulla. In the cords and sinuses you have reticular cells
and fibers.

Slide 43 Spleen
Dr. McCutcheon OK, so the spleen is the LARGEST OF THE LYMPHOID ORGANS. It
has 3 primary functions. Primary function #1 is FILTRATION. What it filters? It
filters 2 separate things. Its job is to remove old red blood cells and platelets
because once the red blood cells or the platelets, their edges arent smooth anymore,
the red blood cells tend to get lodged in capillary beds and the platelets tend to start
clotting. So every red blood cell and platelet passes through the spleen at least once
every 24 hours. So in the spleen its full of macrophages and when the red blood
cells or the platelets start to look worn, the macrophages can phagocytose them. Red
blood cells also have receptors for debris and if the red blood cells have picked up
debris and well talk about this again in the summer, if the red blood cells have
picked up debris then the macrophages can pull the debris off the red blood cells
and eat the debris. So it filters, primary function. Secondary function, its a
RESEVOIR FOR ERYTHROCYTES, PLATELETS, and GRANULOCYTES. In humans it is
NOT a big reservoir but it is a reservoir. The third function is in the event that you
have NOT managed to contain a peripheral infection, and the pathogen is now
circulating in the circulation, the SPLEEN CAN ACT AS A LYMPH NODE. So first
function is filtration, second function is storage, third function is in the even of
an emergency because you have a blood borne pathogen, the spleen can act as
a lymph node. If that is happening you are in DEEP TROUBLE. The spleen has a
capsule like the thymus and the lymph node. It has trabeculae like the thymus and
the lymph node although its not lobulated. It doesnt go that far. In the trabeculae
runs the circulation, so you have the artery or arteriole entering the spleen in each
of the trabeculae and then you have the veins exiting the spleen in the trabeculae.
There is NO CORTEX and NO MEDULLA. The spleen doesnt have a cortex and a
medulla. It does have cords and sinuses. There is no cortex and medulla, there
are cords and sinuses. If you look at the spleen histologically, what you see are
areas that are BRIGHT RED and areas that are NOT BRIGHT RED. The areas that are
bright red are filled with ERYTHROCYTES right? Because the purpose of the spleen
is to filter erythrocytes and thats called the RED PULP. Everywhere that is NOT
bright red is called, by default, WHITE PULP. Thats where the lymphocytes go. So
scattered throughout the spleen, you have these little areas of white or things that
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dont stain red and thats the white pulp and thats where the lymphocytes are. The
lymphocyte areas tend to cluster around the arteriole. Immediately around the
arteriole are T cells and they are in an area called the periarteriolar lymphatic
sheath. Outside, the T cells clustering around the arteriole are the B cell germinal
centers. Then you have a layer beyond that thats mostly macrophages and
dendritic cells, thats the mantle.. or marginal zone, sorry, marginal zone. So the
white pulp is clustered around the artery and then everything else is red pulp. So
the T cells immediately around the artery are called the periarteriolar lymphatic
sheath. The B cell germinal centers are more distal to that and they are surrounded
by a marginal zone that is primarily dendritic cells and macrophages. The rest of
the spleen, the rest of the red pulp is filled with macrophages. So there are
macrophages everywhere.

Slide 44 Untitled

Dr. McCutcheon So there is a capsule. There is NO subcapsular space in the spleen
unlike the lymph node. So here we can see red pulp. We can see an area that is not
red, so the white pulp. There is the central arteriole so its clustering around the
artery. Then some of these are probably medullary .. or splenic sinuses. Some of
them are probably trabecular, from this stain you cant really tell the difference. So
the red pulp is where the cords and the sinuses are. You have areas that have dense
cell populations and then you have areas that have relatively non-dense cells and
those cells are moving in through the sinuses.

Slide 45 The Spleen
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Dr. McCutcheon So cartoon, we can see how the white pulp is a patchwork.. and I
mean this is really throughout the whole spleen. Its not like there are segregated
areas where you have white pulp and red pulp. The white pulp is just little clusters
of lymphocytes scattered throughout this mass of seething erythrocytes. So white
pulp, theres the central arteriolar, nice area of dense red pulp that thins out again to
the white pulp, goes back to the red pulp. Then red pulp then white pulp. So it really
just is a continuous mess of erythrocytes and then you have areas where the
lymphocytes cluster and its in and amongst the erythrocytes.
So here we have our central arteriole. So around the central arteriole is the
PALs so this is a T cell area. B cells are clustering here in the germinal center and
up around through here. You know, supposedly theres a marginal sinus here
although I think thats the histologists trying really hard to find something to call it.
Then as you merge into the red pulp youve got a layer of macrophages and
dendritic cells. Or macrophage, dendritic cell denser area. When I say that it doesnt
mean you dont have macrophages and dendritic cells through the rest of this, its
just that relatively speaking there are FEWER of them than there are B cells and T
cells and in the marginal zone there are MORE of them than there are B cells and T
cells. So its a matter of degree and not an absolute. Up to this point you have B cells
and then you take a step over and then you have macrophages. So its just changing
the density.


Slide 46 Untitled
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Dr. McCutcheon If we have sinuses we have to have some way to keep them open.
The way we keep them open, again, is with reticular cells that have reticular
fibers. So throughout the spleen you have this network of reticular cells and
reticular fibers that are keeping the spaces open.

Slide 47 Untitled

Dr. McCutcheon So that or this (A)? Central arteriole, good. So then the cells around
the central arteriole? PALs is the periarteriolar lymphatic sheath, what cells are in
it? T cells, right. Oh thats what this is, I thought it was a time out. Ok so then this
would be the? (GC germinal center). Ok and what cells are in there? (B cells). So
what cells are denser here (Mn Mantle layer) than they were there? Macrophages
and dendritic cells, good. Then this part up here or over here? Red pulp.

Slide 48 Untitled
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Dr. McCutcheon Alright, so for a long time in the literature, there was this big
controversy as to whether the spleen had a closed circulation or an open circulation.
Closed circulation meant the arterioles became capillaries, beaome venules, became
bigger venules. Open said that the arterioles became capillaries and then the
capillaries ended. Then eventually the sinuses would coalesce to start becoming
venules. Through a truly heroic experiment, because they are proving something
DOESNT exist, they have shown that the capillaries do actually end. So OPEN
CIRCULATION IS CORRECT. This is a paper from 2012, I think, so its not going to
be in any of your textbooks. But open circulation is correct. So the arteriole branches
off into smaller and smaller branches and then eventually it becomes capillaries and
eventually the endothelium goes away. So the erythrocytes are just out in the spleen
hanging out in the cords. They will move around in the cords and eventually they
will migrate into some of the sinus spaces. The sinuses, as they get closer to a
trabeculae, coalesce into little venules. Then the venules coalesce into a bigger
venule and thats what exits in the trabeculae. Eventually, all of the venules coalesce
into the vein, thats the SPLENIC VEIN. So theres a place where you are out of
endothelium. There are no vessels. There is just the red cells getting dumped into
the cords of the spleen.

Slide 49 Untitled

Dr. McCutcheon So here we can see a sinus again, sinus is not an absence of cells,
its just relatively fewer cells and they are migrating somewhere. In between the
sinuses we can see the cords. They have stained this so that you can also see the
reticular fibers helping to hold the sinuses open.
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Slide 50 Untitled

Dr. McCutcheon The capillaries end, cells can wander around, and the sinuses
eventually coalesces into a venule.

Slide 51 Untitled

Dr. McCutcheon So if we look at this we can see nice sinuses. We can see dense
cords filled with cells. Sinuses, cords, sinus, sinus, sinus.

Slide 52 Untitled
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Dr. McCutcheon The sinuses have fenestrated walls so you can see how the cells
can easily move in and out of the sinus. Then yea, cord up here, red pulp,
macrophage, macrophage, probably a macrophage. So lots of macrophages in the
red pulp. The red blood cells, the erythrocytes are moving in and out of the sinuses
into the cords, back into the sinus, back into the cords. Eventually they end up in a
sinus that stops being fenestrated and that makes it a venule. Then the cells will exit
the splenic vein and go back into the circulation unless they were eaten.

Slide 53 Lymph Node, Spleen
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Dr. McCutcheon Ok, so the red pulp does the filtration and the storage part. The
white pulp does the, in case of an emergency, act as a lymph node part. So the point
of this slide is to kind of remind you, like a lymph node, each of the areas of white
pulp does a sort of similar thing. You have an area that is primarily T cells, you have
an area that is primarily B cells, you have macrophages and dendritic cells
throughout but then you have an area of denser macrophages along in through here
(mantle area). OK? So every white pulp spot is its kind of its own mini lymph
node.

Slide 54 Summary
Dr. McCutcheon So we have an encapsulated organ. Its trabeculated but its not in
lobules. There is no cortex and medulla. Instead we have cords and fibers and we
have reticular cells with reticular fibers. Questions about the spleen? Oh, the other
part about the spleen is there is NO LYMPHATIC DRAINAGE INTO AND OUT OF
THE SPLEEN. This is NOT draining the periphery. So No lymphatic draining into the
spleen or out of the spleen. Any pathogen that gets into the spleen, its because its in
the bloodstream.

Slide 55 Tonsils
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Dr. McCutcheon So as dentists, tonsils are your greatest asset and they are your
worst enemy. OK? How many people have every bitten their cheek? How many of
you have been rushed to the hospital for antibiotics? Pizza burn? Antibiotics? When
your teeth fell out as a little kid? Antibiotics? Ok, the reason.. and yet the oral cavity
has more bacteria than anywhere else, not per number but more types of bacteria in
it than anywhere else in the body. So why is it that you dont get an infection every
time you have an interruption in your epithelium lining your oral cavity? The
answer is THE TONSISLS. One of the things that the tonsils do is that they provide a
place for all of the, a sample of all of the bacteria in the oral cavity to reside. So the
bacteria live in the tonsils, and because of that the immune response, especially the
B cells secreting antibodies, are constantly secreting antibodies against ALL of the
bacteria that you have in your mouth. So whenever any of those bacteria end up
getting into your bloodstream through one way or another, they are instantly coated
with antibodies. Then macrophages or monocytes can come along and eat them and
then thats the end of that. So the fact of the tonsils is the reason why people dont
die every time they have a disruption of the epithelium in the oral cavity.
Now if youre a periodontist and you have somebody that has really nasty
perio and you think to yourself, oh gosh lets put them on antibiotics and wipe out
all of the bacteria in their oral cavity, is that going to do you much good? No,
because the antibiotics cant get to where the bacteria are. They are in the oral
cavity and the antibiotics are in your tissues. So you wipe out everything that the
antibiotics could get to and then all of the bacteria from the lymph nodes.. or from
the tonsils can then start replicating again and they will just refill all of the niches. So
antibiotic therapy doesnt work because you have these reservoirs of all of your
bacteria essential for keeping you alive, keeping your immune system at hyper
awareness. It causes a problem when you are trying to treat with antibiotics, which
is why antibiotic therapy has really fallen out of vogue as something to do for
periodontal disease except in acute infections.
So there are 3 sets of tonsils and they basically form a ring around your oral
cavity. 2 of them are on the lateral walls of your pharynx and those are the palatine
tonsils. Palatine tonsils, 2 of them, lateral wall of your pharynx. For those of you
who had tonsillitis as a kid or had a tonsillectomy as a kid, those were the tonsils
that they took out or were infected. So one wall.. so this is the oral cavity here. So the
wall of the tonsil that is exposed to the oral cavity has epithelium. The wall that
would lead into the body has a very thick fibrous connective tissue so that any
bacteria that do happen to get into the tonsil itself are walled off from the rest of the
body. Palatine tonsils have numerous deep invaginations that are called cyrpts and
this is where the bacteria samplings are stored, or one of the places. Then along the
lining of the cyrpts you have B cells, T cells, macrophages, and dendritic cells.
Tonsils, unlike lymph nodes, a lot of the B cells in the tonsils are going to be plasma
cells secreting antibodies. So theres a really heavy concentration of antibodies
right here. OK, so B cells, T cells, macrophages, dendritic cells. Epithelium on the oral
cavity side, thick, thick fibrous connective tissue on the body side. 2 palatine tonsils.

Slide 56 Untitled
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Dr. McCutcheon So here you can see some lymphoid infiltrate underneath the
epithelium. Here you can see a really dense lymphoid infiltrate underneath the
epithelium. There is a crypt.

Slide 57 Lingual Tonsils
Dr. McCutcheon You also have tonsils on the POSTERIOR 1/3 of the BASE OF YOUR
TONGUE. These are called LINGUAL TONSILS. They are basically a little organized
area of lymph tissue sitting within a muscle in the epithelium of the tongue. So youll
have a B cell area, you will have a T cell area. Each lingual tonsil, and there are
hundreds of them, has a single crypt storing all of those wonderful bacteria. It
keeps you alive, it means you cant use antibiotic therapy for much success in
dentistry. Ok, so youve got the tongue epithelium over them. Discreet, organized
areas of lymphoid tissue. Each tonsil has a single crypt. There is NO CAPSULE on the
bottom of this.

Slide 58 -- Untitled

Dr. McCutcheon So we can see our single crypt, ok? Thats a salivary gland area of
lymphoid tissue. Under this stain you cant tell the difference between the B cell and
the T cell areas. Again, the tonsils, a lot of the B cells in the tonsils will be plasma
cells. So these are mature B cells secreting antibodies, large quantities of antibodies.

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Slide 59 Summary
Dr. McCutcheon I realized why I didnt have a picture of the palatine tonsil this
morning when I was looking through my lecture because THATS IT. Ok? You cant
see a palatine tonsil UNLESS its REALLY INFLAMED. So theres this spot on the back
of your pharynx that has actually got some lymph tissue underneath the surface
epithelium and thats the palatine tonsil. No Im sorry, pharyngeal tonsil. Long day,
sorry, sorry, sorry, pharyngeal tonsil. So youve got a single pharyngeal tonsil that is
at the back, kind of at the junction between your oral and your nasal pharynx. Its
remarkably unspectacular so you have epithelium and under the epithelium you
have some lymphoid tissue. You dont have crypts although you do have shallow
invaginations that are called FOLDS. There is a thin capsule on the body side of the
pharyngeal tonsil. One pharyngeal tonsil, no crypts, folds, thin capsule. For those of
you who have ever heard the term ADENOID, if someone has a really nasal voice
they say shes very adenoidal or hes very adenoidal. Well, thats the adenoid. So
when that gets really swollen it makes you sound all twangy. So palatine 2
tonsils, mini crypts, partially encapsulated. Pharyngeal 1 tonsil, folds,
partially encapsulated. Lingual lots of tonsils, single crypt, no capsule. And I
will post this on classes this afternoon or tomorrow morning.

Slide 60 M-ALT
Dr. McCutcheon Were into the home stretch, so there ..are anywhere that you have
contact with the outside, you need to have lymphatic tissue. We call these
associated lymphatic tissues because the organ that they are in changes the first
letter. So if they are in the bronchioles, they are B-ALT, bronchial associated
lymphatic tissue. If they are in the GUT they are G-ALT, gut associated lymphatic
tissue. If they are in the MUCOSA, they are M-ALT, mucosa associated lymphatic
tissue. They are essentially little areas of lymphatic tissue sitting in the lamina
propria of whatever organ it happens to be in. So their function is to do what the
immune system does, to find things that dont belong and make sure we get rid of
them before they do damage.
In the gut, this cartoon you have a B cell area, you have the germinal center
which is the proliferating B cell area. It is surrounded by a T cell area. Remember
this is NOT a 2 dimensional structure so the B cell area looks like a golf ball and the
T cell area looks like a hat on the golf ball. One of those baseball caps that doesnt
have a part that goes over the top of your head, just a rim. So thats what the T cell
area looks like. So dense lymphatic tissue. This is gut. There is gut epithelium, area
of lymphatic tissue.

Slide 61 Untitled
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Dr. McCutcheon In the Peyers patches in the gut, there is also a SPECIALIZED
EPITHELIAL cell called an M-CELL. The gut needs to do something that you dont
have to have in the M-ALT or the B-ALT, thats because in the gut you have constant
challenge by antigens otherwise known as FOOD. Ok, and if your immune system
started making an immune response against all the protein and carbohydrates that
you eat, then you wouldnt be able to eat and then you would die. So part of what the
M cell does is it presents antigens in such high concentration that it overwhelms the
immune system and that develops tolerance. So you are TOLERANT TO YOUR
FOOD. So the M cell is an epithelial cell and it does TRANSCYTOSIS. It grabs things
from the lumen of the gut and it transcytoses them through its basement membrane
into this area where you have B cells and T cells and macrophages and dendritic
cells.

Student Question Could this be related to celiac disease?

Dr. McCutcheon I havent read about celiac disease in a while. So I dont remember.
I didnt think that was auto-immune.
So and again, because this is the gut and you have constant antigenic
challenge, some of those B cells are actually going to be plasma cells secreting
antibodies against things that you dont want. But you have this really uniquely
shaped cell. It has pushed the nucleus off to the side and it is quite large so that you
have a room to have B cells and T cells and macrophages and dendritic cells all
housed under just 1 thin layer of cell and you are trancytosing antigens or stuff here
and the B cells, T cells, macrophages, and dendritic cells can pick up stuff and decide
what they need to do with it. Alright, so thats in the Peyers patches in the gut.

Slide 62 Untitled
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Dr. McCutcheon So again, you have a normal gut. This is muscle, lamina propria,
and in here just underneath the epithelium you have this area of DENSE little
lymphocytic infiltrate. So these are going to be throughout the length of the large
and small intestines. Just little areas of lots of lymphatic tissue.


Slide 63 Untitled Diagram

Dr. McCutcheon Now one of the interesting things, and you know this statement
will come as a shock we are going to talk about it more in the summer, where the
lymphocytes first get activated, and by the lymphocytes here I really mean the B and
the T cells. Macrophages and dendritic cells and neutrophils are N stage cells (Or
end stage cells?). If they end up in the G-ALT, they are going to stay in the G-ALT for
their lifespan and then they will die and be replaced by new ones. But the B and T
cells, once they are activated, part of the cells become memory cells and they live
for decades. If the B and T cells are activated against a pathogen in G-ALT, although
they may go back into the circulation, they end up homing back to the gut. Cells that
were activated against something in the bronchi, they will go out into the circulation
but they end back up in the lymphatic tissue in the bronchi. Which makes sense,
right? Because pathogens that are in the bronchi where you want the antibody
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secreted are not likely to be in the gut so whats the point of having antibodies
against something that you breathed in in your stomach, or your intestines, and the
converse? So lymphocytes that were activated in a lymph node, they will tend to end
back up in lymph nodes although some of the plasma cells will be in the bone
marrow so you get body body-wide coverage of antibodies in case any of the
pathogen has leaked into the circulatory system.


Slide 64 Untitled Table

Dr. McCutcheon So you have this trafficking of lymph nodes coming out and
circulating and going back. The nave cells just keep going from place to place to
place. The memory cells will go back to wherever it was they were made. It might
not be the exact same peyers patch but they will end up in a peyers patch. All of
that happens through molecules called ADHESIN molecules and SELECTINS and we
are going to talk about this in greater detail in the summer. OK? Thats my last slide.
Do you want me to go back to the objectives and review?

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Slide 5 Objectives
Dr. McCutcheon OK, so we are going to describe the cells of the lymphatic system.
Identifying the function is, you know, a brief description. So phagocytic cells. Which
cells are phagocytic? Macrophages, neutrophils, dendritic cells. So for now, thats
enough function. Those 3 cells are phagocytic. So natural killer cells are a part of the
non-specific immune system but they are not phagocytic, they do other things and
we will talk about that. Then we have 3 rarer non-specific cells, which are mast
cells, basophils, eosinophils and they DEGRANULATE. Then our antigen specific
cells are what? Antigen specific, oh there someone said it. B and T cells. T cells
divide into what groups? CD4 and CD8. CD4s have a subset, T regs. Good, then the
unconventional T cells? Alpha and Beta are the conventional. Gamma and delta are
the UNCONVENTIONAL. B cells, you have conventional and then you have
unconventional which are CD5. The gamma delta T cells and the CD5 B cells live in
the tissues as opposed to the peripheral circulation. So that the gamma delta T cells
start off in the bone marrow, they mature in the thymus. As mature cells they hop
into the circulation long enough to get to a tissue and they live in a tissue. The
conventional B cells develop in the bone marrow, they go off to the tissue and they
stay there.
Anatomic and histologic structure of lymph node, including how cells enter
and exit the lymph node. Someone want to tackle that? Its not a test, yet. Antigen
comes from the afferent, B cells and T cells come from the HEV. Where do the B cells
and T cells go? (Student response cant be heard) OK good. What other kinds of cells
are in the lymph node? Macrophages, dendritic cells, and not really a lymphocyte
but reticular cells. Good. Generally the thymus is an..? Generally the thymus is an..?
Surrounded by a? CAPSULE. Its an ENCAPSULATED ORGAN. It has trabeculae and
then mature, proliferating, activated cells exist through the..? Exit the lymph node
through the EFFERENT lymphatic. Although, officially those are pronounced AFF-
ERENT and EFF-ERENT, its much easier to tell what I am saying when I say A-
fferent and E-fferent thats why I mispronounce them like that. OK, so whats the
function of the lymph node? Its not a well it filters but thats not really the
function. Thats a byproduct. [Student responses cant be heard]. What about it?
Nope. Its got one main purpose. So capturing the pathogens is a byproduct. But that
is on the right track. Its a MEETING PLACE. The purpose of the lymph node is to get
the pathogens from the periphery to the lymph cells from the circulation. In the
process it does some filtering and it does some capturing but the purpose of the
lymph node is to get the stuff from the periphery to meet the stuff from the
circulation. So its a meeting place.
Cells in Peyers Patches. M-ALT is another name for peyers patches. So an M-
cell. Macrophages, thats a good guess. 3 more. (Student responses cannot be heard).
B and T cells. 1 more. Dendritic cells. OK, and what is the purpose of a peyers patch?
Its a MEETING PLACE. The purpose of a peyers patch is so that you have
somewhere that the antigens from the periphery meet the stuff in the tissue. So its
to get everything that is in your gut introduced to B and T lymphocytes which may
or may not have ..against which they may or may not have a response. So the
purpose of all the associated lymphatic tissues are as a MEETING PLACE.
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OK, functions of the tonsils. MEETING PLACE! Good, its a meeting place. It
also acts as a RESERVOIR FOR BACTERIA to keep your immune system on HYPER-
ALERT status against the pathogens in the oral cavity. But its a meeting place.
Getting a theme here? OK, histological structure of the spleen and what are its
functions? Filtration and storage and? It acts as a lymph node which makes it a
MEETING PLACE. OK, the one organ that we talked about that is NOT a meeting
place is the THYMUS. OK? All the rest of these do the same thing. Its a meeting
place. Pathogens meet B and T cells. Structure of the spleen, it has red pulp and
white pulp. It is surrounded by a capsule. It has trabeculae. What is in the
trabeculae? Arterioles and venules. What surrounds the arteriole? White pulp
starting with the T cells, right. Outside latter to the T cells are the germinal centers.
Lateral to that is the ..germinal centers are in the B cells (?), so lateral to the
germinal centers are the marginal areas.
So we have red pulp, white pulp. What is the structure of the red pulp? C&M..
C&S sorry, CORDS and SINUSES. OK? So most of the cells are where? In the cords.
What keeps the sinuses sinuses? Reticular cells. Then the sinuses do what? Coalesce
to become venules. Then the venules exit through the trabeculae.
Thymus, function of the thymus? It makes T cells. Structure of the thymus?
Encapsulated, cortex, medulla, reticular cells. So you have THYMIC RETICULAR
CELLS.. NOT reticulocytes. Different thing. OK, you have .. charades. 2 words, its bi-
lobed and partial lobules caused by? Septae, ok? That is this. So we have the cortical
epithelial cells and we have the reticular cells and then we have medullary epithelial
cells which are reticular cells. What other cell type do we have a lot of in the
thymus? Lots and lots of MACROPHAGES. What are the age related changes in the
thymus? Yup, the thymic tissue gets replaced by ADIPOSE tissue.
OK. Dr. Schiff is here, I guess you guys can get a few minutes break. OK so let
me put in a plug for this summer. Immunology, one, immunology is a circular
subject so no matter where we start there are always things that have happened
beforehand. So I teach it as logically as I can but I cant teach it completely logically
because it isnt logical. Second, a lot of what I need for you to do this summer is
understand things. It is beyond memorization, you have to actually figure out how it
works and its a BUILDING CLASS so if you dont understand the first lecture, then
when you get to the second lecture you are going to be even less understanding. By
the time we hit the third lecture you are going to be LOST. So its really important to
keep up. For the most up, the lectures are SPACED OUT so you have time to think
about what you have learned rather than, ..so you need to do that. The people who
do well in this, and this is the basis for almost all the pathogenesis of disease that
you are going to learn. So if you dont understand immunology you are not going to
understand disease. You figure out the immunology, the disease is a lot easier to
understand. The people who do well in this study throughout. The people who
decide that they always studied 2 days before the test, they can do this for
immunology, they tend to do really poorly. So if you ask the rising D3s and they say,
oh no, I studied 2 days before the test, ask them how they did because they didnt
do very well. So this is different than other things that you have done. So, accept that
and try to approach it differently rather than trying to do what you have always
done. For those of you, I mean some of you are really good and you study everything
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all the time, but those of you who like to wait until the last minute, dont do that for
immunology. OK? I will see you in the summer.