58: lymphoid organs ii

Transcribed by Leslie Afable 5/16/14

Organ Systems Lecture 58 – Lymphoid Organs II by Dr. McCutcheon

Slide 33 – Lymph Node- Meeting For Periphery and CirculationDr. McCutcheon – Alright, so yesterday we started with the lymph nodes so to remind you, the lymph node is a what? It’s encapsulated. What’s this? The afferent lymphatic. What’s this? Pardon? Paracortex. What’s 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, there’s the schematics of organs when they show a SINUS it has NO cells in it. That’s 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. That’s mostly B-cells. So if we come down here, again, so this is in the medulla and this is a sinus but again it’s going to have cells in it. It just doesn’t 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). What’s 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?


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Germinal Center


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 that’s what makes a sinus a sinus. Otherwise it would just fill in with cells.


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 it’s sort of circular. I teach it as linearly as possible but it’s not possible to teach it linearly

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Reticular Cell

Reticular Fiber


because it’s 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 we’ve 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. That’s 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 that’s a macrophage full of apoptotic B-cell bits. But remembering that there are lots and lots of macrophages in germinal centers is really important.


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 doesn’t, but if you look on older slides you see this MANTLE ZONE of the GERMINAL CENTER. Germinal centers are usually NOT ROUND, ok so you’ve got the cap, the mantle zone here, and the apex there. I don’t think there’s a reason for that, it’s just the way the cells happen to cluster.


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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 lot’s of no’s, the no’s have it. Instead, these are actually the endothelial cells and instead of being thin and flat, they are ROUND and PUFFY. Ok? It’s a venule and you’ve 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 let’s 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 – SummaryDr. 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 o’clock 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 that’s 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 NodesDr. 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 – SpleenDr. 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. It’s job is to remove old red blood cells and platelets because once the red blood cells or the platelets, their edges aren’t 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 it’s 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 we’ll 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, it’s 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 it’s not lobulated. It doesn’t 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 doesn’t 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 that’s called the RED PULP. Everywhere that is NOT bright red is called, by default, WHITE PULP. That’s where the lymphocytes go. So scattered throughout the spleen, you have these little areas of white or things that

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don’t stain red and that’s the white pulp and that’s 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 that’s mostly macrophages and dendritic cells, that’s 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.


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 it’s clustering around the artery. Then some of these are probably medullary .. or splenic sinuses. Some of them are probably trabecular, from this stain you can’t 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. It’s 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, there’s 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 it’s 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 there’s a marginal sinus here although I think that’s the histologists trying really hard to find something to call it. Then as you merge into the red pulp you’ve got a layer of macrophages and dendritic cells. Or macrophage, dendritic cell denser area. When I say that it doesn’t mean you don’t have macrophages and dendritic cells through the rest of this, it’s 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 it’s 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 it’s just changing the density.


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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.


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 that’s 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.


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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 DOESN’T exist, they have shown that the capillaries do actually end. So OPEN CIRCULATION IS CORRECT. This is a paper from 2012, I think, so it’s 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 that’s what exits in the trabeculae. Eventually, all of the venules coalesce into the vein, that’s the SPLENIC VEIN. So there’s 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.


Dr. McCutcheon – So here we can see a sinus again, sinus is not an absence of cells, it’s 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.


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.


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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 it’s kind of its own mini lymph node.

Slide 54 – Summary Dr. McCutcheon – So we have an encapsulated organ. It’s trabeculated but it’s 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, it’s because it’s 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 don’t 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 that’s the end of that. So the fact of the tonsils is the reason why people don’t die every time they have a disruption of the epithelium in the oral cavity.

Now if you’re a periodontist and you have somebody that has really nasty perio and you think to yourself, “oh gosh let’s 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 can’t 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 doesn’t 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 there’s 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.


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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 you’ll 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 can’t use antibiotic therapy for much success in dentistry. Ok, so you’ve 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? That’s a salivary gland area of lymphoid tissue. Under this stain you can’t 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 – SummaryDr. McCutcheon – I realized why I didn’t have a picture of the palatine tonsil this morning when I was looking through my lecture because THAT’S IT. Ok? You can’t see a palatine tonsil UNLESS it’s REALLY INFLAMED. So there’s this spot on the back of your pharynx that has actually got some lymph tissue underneath the surface epithelium and that’s the palatine tonsil. No I’m sorry, pharyngeal tonsil. Long day, sorry, sorry, sorry, pharyngeal tonsil. So you’ve got a single pharyngeal tonsil that is at the back, kind of at the junction between your oral and your nasal pharynx. It’s remarkably unspectacular so you have epithelium and under the epithelium you have some lymphoid tissue. You don’t 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 she’s very adenoidal or he’s very adenoidal. Well, that’s the adenoid. So when that get’s 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-ALTDr. McCutcheon – We’re 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 don’t 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 doesn’t have a part that goes over the top of your head, just a rim. So that’s what the T cell area looks like. So dense lymphatic tissue. This is gut. There is gut epithelium, area of lymphatic tissue.


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Dr. McCutcheon – In the Peyer’s patches in the gut, there is also a SPECIALIZED EPITHELIAL cell called an M-CELL. The gut needs to do something that you don’t have to have in the M-ALT or the B-ALT, that’s 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 wouldn’t 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 it’s 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 haven’t read about celiac disease in a while. So I don’t remember. I didn’t 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 don’t 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 that’s in the Peyer’s patches in the gut.


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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 what’s 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 naïve 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 peyer’s patch but they will end up in a peyer’s 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? That’s my last slide. Do you want me to go back to the objectives and review?

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Slide 5 – ObjectivesDr. 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, that’s 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. CD4’s 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? It’s 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 can’t 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. It’s 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, it’s much easier to tell what I am saying when I say “A-fferent” and “E-fferent” that’s why I mispronounce them like that. OK, so what’s the function of the lymph node? It’s not a …well it filters but that’s not really the function. That’s a byproduct. [Student responses can’t be heard]. What about it? Nope. It’s got one main purpose. So capturing the pathogens is a byproduct. But that is on the right track. It’s 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 it’s a meeting place.

Cells in Peyer’s Patches. M-ALT is another name for peyer’s patches. So an M-cell. Macrophages, that’s 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 peyer’s patch? It’s a MEETING PLACE. The purpose of a peyer’s patch is so that you have somewhere that the antigens from the periphery meet the stuff in the tissue. So it’s 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, it’s 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 it’s a meeting place. Getting a theme here? OK, histological structure of the spleen and what are it’s 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. It’s 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, it’s 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 can’t teach it completely logically because it isn’t 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 it’s a BUILDING CLASS so if you don’t 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 it’s 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 don’t 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 D3’s and they say, “oh no, I studied 2 days before the test,” ask them how they did because they didn’t 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, don’t do that for immunology. OK? I will see you in the summer.

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58: lymphoid organs ii

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