WK 1b Lymphoid organ and Immune system

So the anatomy of the immune system and hematopoiesis, that cellular process. Okay.

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Learning outcomes for today then. We're going to be looking at the anatomy of the immune system, particularly the lymphoid organs.

So it's the lymphoid organs that we're looking at in the first part. The lymphoid organs are the sites of blood cell production, blood cell or at least the immune cell maturation and where the immune cells then function and finally where most blood cells are destroyed. So we're going to look at those different locations. How does this map onto our module learning outcomes?

As we covered earlier in the week, the top half is all about hematology. This really is part of that basics of immunology, looking at the anatomy and physiology of the organs and tissues of the immune system.

Textbooks. Right.

So we did a bit of a recap on Tuesday and I referred you back to your first year lectures, if anything didn't make sense, to go back to those first year lecture notes to make sure you're up to speed on the functions of each of the different blood cells. When we look at the anatomy of the immune system, we're going to be mostly focusing on obviously the white blood cells. So we've got the granular sites up at the top there, basophils, neutrophils, eosinophils, and then down at the bottom here are agranular sites, which is our lymphocytes and then monocytes. Where are these produced?

Where are these functioning? Where it's all happening in the lymphoid organs, the lymphoid organs.

So we're looking to start with at the primary lymphoid organs.

Now the primary lymphoid organs are our bone marrow and the thymus. So we'll start with those two, the bone marrow being the site of production of all blood cells, not just the immune system, but all blood cells. Some cells go off to the thymus for maturation. And then the secondary lymphoid tissues, these ones in blue. So we've got things like the tonsils, the lymph nodes, the lymphatics, payers patches in the gut. And then we'll be looking lastly at the spleen as the site of blood cell destruction, where old blood cells go to be destroyed, but also a storage site.

We use it to store lots of blood cells as well. So let's kick off then with the primary lymphoid organs.

We're going to start with the bone marrow.

So the primary lymphoid organs, site of blood cell, in this case immune cell production, and then the maturation of the T lymphocytes, T lymphocytes, T for thymus, T lymphocytes happens in the thymus.

So the bone marrow.

The bone marrow is the site or the main site of adult hematopoiesis.

So hematopoiesis, we've got a separate lecture on after this one.

Hematopoiesis is the maturation of the blood cells. And it takes place in the bone marrow in adults. So in you and me, it's happening in our bone marrow. In adults, the main site of hematopoiesis is the pelvis.

So the pelvis, you've got your pelvic bones here, the anominous, so our pelvic bones, but also taking place in the sternum, your breast bone, the vertebrae, so the bones that make up your spine, the ribs.

And then we have a little bit happening in the heads of the femur and the heads of the humerus.

So with our long bones, you have one end, which is like the epiphysis, and then you have the shaft, which is the diaphysis. Think back to part one.

So it's in the epiphysis that we have blood cell production, both in the femur, and we can see up in the humerus here as well. We're going to talk a bit more, well, a lot more about hematopoiesis in the second lecture.

So the bone marrow is the spongy tissue inside bones that within the bone marrow, we have a range of different cells. We have our hematopoietic stem cells, the ones which are going to mature into the different blood cells, and then we have what's called stromal cells, and these provide the environment, and they secrete all kinds of growth factors that tell those immature blood cells whether they're going to become a red cell or which are the white cells or a platelet. So we have growth factors that tell the maturing cells what to become.

Bone marrow consists of red marrow and yellow marrow. So it's the red marrow that is where the blood cells are produced, and that's mostly found in the flat bones. So the pelvis, the sternum, the ribs, these are all examples of flat bones.

The vertebrae are an example of an irregular bone, and of course you've got the the long bones, the humerus and the femur, a small amount of production in those. You'll see more detail on that in the next lecture. The yellow marrow is found mostly in the shaft of the long bones, and it's involved in some of the white cell production, but generally not where the blood cells are produced.

So as I say, we're moving on to the thymus then.

Tea lymphocytes are called tea lymphocytes because they go to mature in the thymus.

So the thymus is our site of T cell maturation.

People often get confused between the thymus and the thyroid.

So the thymus in this picture here is the bit that's shown in green.

It's located behind your sternum, so it sits behind the breastbone, and it's lower down than the thyroid. Here's the thyroid in your neck, and that sits the front of your neck here, and that's where we produce things like thyroid hormones.

What we're interested in today is not the thyroid but the thymus, the thymus.

So the thymus is located in what's called the mediastinum. The mediastinum is the area that sits between the two lungs. So it contains lots of things, mostly the heart.

So here's our mediastinum, and we can divide it into a superior mediastinum, which involves the aortic arch and above the heart, and then the inferior mediastinum, which is most of the heart coming right down.

So it's the area between the lungs, so it comes right down following the diaphragm here.

The inferior mediastinum can be divided into an anterior, middle, and posterior regions.

So the bit in front of the heart, the heart, and then the bit behind the heart. Where the thymus is located is in this region of the upper or superior mediastinum, and then the anterior mediastinum.

So it sits just behind the breastbone, just in this area here.

If it sits behind the sternum, it's also described as retro sternal, retro sternal.

Behind the sternum, and because it sits in front of the heart, it's in front of the pericardium, in front of the sac or the bag that surrounds the heart. As I said, the thyroid gland is much higher up in the neck. When we look more closely to its structure, as you can see from the picture here, it's bilobed, so it's got a left and a right hand side, so a left lobe to the thymus, and the right lobe to the thymus.

They're asymmetrical, they're not identical, they're a bit squiffy in shape.

And we can divide the thymus into different layers, so it's got an outer cortex and an inner medulla. Now this idea of having an outer cortex and an inner medulla, we come across in lots of different tissues. Think back to your part one, do you remember kidneys?

The kidneys had an outer cortex and an inner medulla. You might not yet have covered the adrenal glands as part of endocrinology.

Again, it has an outer cortex and inner medulla, so it's just quite a common tissue structure.

So outer cortex, inner medulla. It's where the T cells, the T lymphocytes, are going to go to mature. So immature T cells are also known as thymocytes, thymocytes, because they're going to the thymus to mature.

As they are more specialized, and we also destroy a huge number of them. And we'll talk about that possibly on the next slide.

So we're going to get rid of, we're going to destroy a huge number of T cells, because we don't want to keep the T cells that recognize our own body tissues. If we have T cells that recognize us, our own tissues, whether it's our joints or our heart or our blood cells, then that would cause autoimmune diseases.

We would attack our own body tissues. So we're going to destroy and get rid of all of those self-targeting T cells.

So we're going to get rid of about 95, 98% of the T cells, because they'd be against self. We're going to keep only those T cells that would recognize something from outside of the body, something foreign, bacteria, viruses, foreign substances. So clinical relevance of all this then is when it goes wrong, people do end up with autoimmune diseases. And we've got a whole lecture on autoimmune diseases in the second half of the module. So you'll be learning about conditions like rheumatoid arthritis, type 1 diabetes, various other autoimmune disorders. So this is looking more closely at the thymus. We can see in the picture here those different layers.

So in blue, we've got the cortex, so the outer cortex.

And then in kind of orangey, we've got the medulla, the inner medulla.

And it's as the immature T cells travel through from the outer cortex going in towards the center, that's when all this sorting and processing goes on.

So as they go through the cortex, these immature T cells traveling or migrating through the cortex here, they undergo what's called positive selection. Positive selection means we're choosing to keep those T cells which are functional.

So we don't know what they're raised against yet, but are they functional? Do they have a functioning receptor on their surface? So positive selection for functional receptors on the surface. Then as they go into the next bit here, which is this border, the cortex-medulla border where the two zones meet each other, this is where we go through negative selection.

Negative selection is getting rid of those T cells against self. We're going to get rid of, we're going to destroy all of the T cells that recognize bits of you.

We don't want those T cells escaping into your circulation where they then go and attack bits of your body. So we've got positive selection in the cortex, negative selection at the border. And then in the medulla here, shown in yellow, we've got our macrophages. So they're starting to get rid of all of those ones which were destroyed, the ones we've said to get rid of. And then in the medulla itself, we have what's called differentiation. Differentiation is when cells become more specialized into their function. So with T cells, as we'll see later in the module, we've got different types of T cell. The two main types of T cell are T helper cells and T cytotoxic cells. And they do what their name suggests. The T helper helps raise an immune response. The T cytotoxic is site, that means cell, toxic, toxic, cell killing. So T cytotoxic cells are going to do the killing of cells we don't want in the body and the helpers do a lot of helping. So it's in the cause, sorry, in the medulla that we've got this differentiation.

They finally become their mature version, either T helpers, T cytotoxic, or some of the other types of T cell. Throughout this whole process then, we're going to get rid of about 95 to 98% of the T cells. They'll never be used.

So they need to be destroyed by apoptosis and engulfed by macrophages. Okay.

Happy with the thymus. Yeah. You'll come back to this a few times in the module. So as I said, we've got autoimmune diseases. You'll be looking at it a reminder then. And also, Andrew, Dr.

Andrew Biklle might touch on this a little because he'll be talking about the T cell receptor genetics.

He'll be talking all about the genetics behind the T cell receptor. How is it that we can produce T cell receptors that can recognize millions of different things, things that we've never seen before, things that we have seen? How is it we can produce so many different varieties of receptor to recognize different pathogens, different viruses, different bacteria, and so on?

Okay. So that's called immunogenetics. And that's one of the topics that Andrew will talk about.

Okay. Thymic involution. If we look at the size of the thymus in a 10-year-old, it's really quite large. That's the thymus, not the heart. It's quite big. And then as we get older, it shrinks. It shrinks and shrinks and shrinks. So when we are born, it weighs about 20 grams. It's its biggest size when we're about 10, which makes sense. Picture in your mind a typical 8 to 10-year-old walking to school. Chances are they've got a snotty nose.

Okay. Their bodies are learning to deal with all sorts of different bugs. Their immune system is still maturing, and they're gaining that memory, that experience of different infections.

So their thymus is having to work super hard. They're producing loads and loads of different T cells and then getting rid of lots of them. So that's when it's at its biggest. And then our thymus starts to shrink. So by your age, it's back down to the size it was when you were born. Pretty much, but you're much bigger. And then as we get older, it gets smaller and smaller and smaller until it pretty much just becomes a bit of fatty tissue about the size of the button.

So tiny. So this possibly contributes towards why the elderly are less able to deal with new infections.

So as we get older, our immune system declines. It's not great when we're little. It's immature.

It hasn't developed. It gets better in our early years, young adulthood. And then our immune system starts to decline. Now, when it comes to T cells and memory, you have to remember that by the time we get to this age, we've seen a lot of infections. So our memory and our ability to deal with infections we've seen before is not too bad.

But our ability to deal with infections that we've never seen before, not so good. This is why when COVID came along, the people who were at most risk, they're very young, they're very old, and the people whose immune systems don't work so well.

Yeah? So this is part of what's going on with it. So although when you're older, you've got great memory for immune stuff, not so good at raising new responses. Okay, true or false?

The pelvis is the main site of normal adult hematopoiesis. That one's true.

The thymus is the site of T cell production. False.

Always remember bone marrow is where they're all produced.

T cells do go to the thymus for the maturation, but they're produced in the bone marrow. The thymus sits in the middle media stynum.

False. So it was the upper and anterior, wasn't it?

Okay, let's take 30 seconds, decompress, and then we'll carry on with the secondary organs. Okay, let's carry on then.

So primary lymphoid organs, bone marrow and thymus, secondary lymphoid organs, tonsils, lymph nodes, lymphatics, pears, patches, and spleen. Let's kick off by looking at the lymphatics.

So the lymphatic system is another part of our circulatory system. We've got arteries, veins, capillaries.

We also have lymphatics. What happens with our lymphatics is that fluid leaves the blood vessels. So here up at the top, we've got in pink, we've got some capillaries with the tissue spaces in between and interstitial fluid.

So liquid will leave the blood into the tissue spaces.

Some of that fluid will go back into the capillaries, back into the blood vessels, but some of the fluid will go into our lymphatic capillaries instead.

Lymphatic capillaries are lymphatic. One starts with a dead end, like a cul-de-sac.

So you've got dead ends here. The fluid goes into the lymphatic vessels and we lose about four liters per day fluid going into the lymphatic vessels.

Once it's in the lymphatic vessels, that fluid is known as lymph. So tissue fluid becomes lymph and then it travels in the lymphatic vessels. The lymphatic vessels themselves have got another picture in a minute, show it a bit better. They are a similar structure to veins. So they've got valves to stop the fluid going backwards.

So if the vessels get squished, just like veins, if it gets squished, the fluid moves upwards or along the vessel, but it can't go the other way because the valves stop it going back again. So every time we walk and we press with our calf muscles squeezing, then we compress the blood vessels, the venous system, all the lymphatics goes uphill because it's not being pumped. It's not under the pressure of the heart, is it? It's not being pumped. We need muscles, squeeze the vessels, the liquid goes uphill and it can't drop back down again. Squeezed again, goes up a bit higher, can't drop back down.

So it travels up. We've got lymphatic vessels all over the body and it passes through lymph nodes.

So at various places, this lymphatic fluid is going to go through lymph nodes. Here's a lymph node here. We'll talk more about lymph nodes in a minute. The fluid will go through about eight to ten lymph nodes as it makes its way. Let me use the pointer instead.

Wherever it started, it might have started down in the legs, it's going to come up.

It hits this main vessel, main lymphatic vessel called the thoracic duct, the thoracic duct here, and that thoracic duct drains into your left subclavian vein. So it goes back into your blood supply. Your left subclavian vein sits just under your left clavicle.

Can you find your clavicle? Find your collarbone on the left hand side.

So just behind that is where all of your lymphs from the lower part of the body and the left arm, all of it goes into that left subclavian vein. Going into the right hand side is just the right arm on the right side of the head and a little bit of the right chest.

Most of the body, the lymphatics from most of the body go in on the left, a little bit just for the right.

So here we can see that a bit clearer. So we've got the lower body, both legs, abdomen, pelvis, left arm, left side of head, all drains into the left subclavian vein.

Right head, right arm, right chest drains into the right hand side.

The main vessel, the biggest of the lymphatics, so it's running next to the aorta, the vena cava. We also then have the thoracic duct and the thoracic duct starts at the bottom here. This is called the cisterna chile.

It's a little pouch, so the vessels from the legs come up and drain into that little pouch, the cisterna chile. From there it moves, the fluid moves up and into that left subclavian vein. So as thought to be, you can all do some citizen science if you want.

Sometime you fancy checking out the smelliness of your armpits. Do you think that you have a smellier left or right armpit? So there's different theories with this. One is that the left hand side of the body has a lot more drainage from a lot more places, so you might expect the left to be smellier. Others suggest that because the right hand one is draining things like the liver and the liver is involved in processing all sorts of things like hormones and so on, particularly when you're stressed, when it's put under pressure.

Some people suggest the right hand side is smellier, particularly at times of stress or intense brain activity. So next time you've got a deadline or an assessment or a test, you can do the sniff test and see what you think is going on.

Okay, here's our picture of the lymphatic vessels. So they do look similar to veins. So here, if we want fluid to go uphill, we have to squeeze it to push the fluid up, but it can't drop back down because of the valve. We squeeze it, it'll go a bit higher and it can't drop back down again.

So it's movement from things like walking, from moving our bodies that helps move lymph around the body.

If you sit still or if your elderly friends and relatives sit still, what happens? They get puffy ankles. It's because they're just not moving, they're not using their muscles to squeeze those blood vessels. If you sit on an aeroplane, you get puffy because partly, fortunately with altitude, but partly because you're just sitting still for a long time.

So movement is super, super, super important.

Moving on from the lymphatics then, the vessels, we then got the lymph nodes. Now, the lymph nodes, we've got five to six hundred of them in the body. I'm not expecting you to memorize and learn every single one of them, not yet in your careers. Depending on what you go on to do, you may or may not need to know these. I think for most of us, we need to know the main ones. So let's look at the main groups of lymph nodes.

The first group is known as the pericranial ring, the pericranial ring. These are the ones that sit under the jaw line here, around the jaw.

So the pericranial nodes, these are draining the face and the mouth. So things like the teeth, if you have a tooth infection, your lymph nodes around the jaw are likely to swell up. Also draining the ear.

So if you had an ear infection, draining the scalp. We don't often get scalp infections, but if we had a cut, we might end up with an enlarged lymph node from infection. Coming down the neck, we've got the cervical lymph nodes, the cervical lymph nodes. So these cervical lymph nodes, these ones are draining from the tonsils.

So if you had tonsillitis, you'd expect the cervical lymph nodes to become enlarged. They're also draining the nose, the nasal cavities and the sinuses, so sinusitis, and the throat, so the pharynx, if you had pharyngitis.

Under the armpits in the axilla, you've got the axillary nodes.

So the axillary nodes drain the arms. So if you were doing gardening and you got a cut that got infected in your hand, then we might expect to see some swelling in one of the nodes or one or more of the nodes in the armpit. Also draining the breast and the thoracic and abdominal wall.

So the outer parts of the thorax outside of the rib cage. We've got some deep nodes, so things like the thoracic nodes and the abdominal nodes and the pelvic nodes.

They drain things like structures in the chest, structures in your abdomen and the pelvis and so on.

So gut, that sort of thing. The inguinal nodes, these are the ones that I describe as sitting along your pant line. If you're wearing a pair of pants or briefs, then they sit along along that line. They're all your groin, okay.

What do they drain? They drain along with the femoral nodes. The femoral nodes come down the inner thigh and they drain the legs and the genitalia. So if you had, again, if you trod on a rusty nail and you had some injury to your foot that got infected, then we might expect to start seeing enlarged lymph nodes in either the inner thigh or the groin.

So lymph nodes themselves, they are a bean-like structure, so an encased or encapsulated bean-like structure, and they are packed full of lymphocytes.

They're called lymph nodes because they're full of lymphocytes. That's why they're called lymph nodes.

They are also full of other white blood cells like macrophages, our dustbin men, and dendritic cells, which are good at presenting antigens.

They sit at the junction of lymphatic vessels. So we could have, for example, in this one, three lymphatic vessels coming in. The fluid gets filtered and then the fluid goes out the other side.

The lymph goes through about eight to ten of these on its journey from the tissues around your body before it goes back into your left subplagium vein.

So eight to ten nodes. Incomplete phagocytosis, so remember the macrophages, phagocytosing, if they're not able to do that completely, if they're overwhelmed, if there's more pathogen than they can deal with, then the lymph node starts to get enlarged and inflamed. So inflamed and enlarged. An enlarged lymph node is known as lymphadenopathy.

Lymphadenopathy. Enlarged lymph nodes. So I'm sure most of you know if you have tonsillitis, they get enlarged lymph nodes, yeah?

They start to swell up. Lymphadenopathy. If we look more closely at the structure of a lymph node then we can look and see it's got yet again an outer cortex and an inner medulla. It's a common pattern we see.

In the outer cortex we have these things here called primary follicles. Primary follicles.

Primary follicles are groups of unactivated B cells.

Unactivated B cells. B cells are our antibody producing cells.

B lymphocytes, they're a type of lymphocyte and they're the ones that produce antibodies. So in the cortex these primary follicles of unactivated B cells.

In the paracortex it's mostly T helper cells. Their role is going to be to help activate the B cells.

And then in the center in the medulla we've got the macrophages, the dustbin then.

And these are going to phagocytose any pathogens that have been marked for destruction or any debris that's left behind.

So cortex. Inactive B cells. Paracortex T helpers.

Medulla macrophages.

So what happens when you step on a rusty nail then?

We get some pathogens coming in. They are able to invade and got past our barrier of skin.

And they're met by dendritic cells. So dendritic cells are a type of antigen presenting cell.

Antigen presenting cells. They're able to take on board that pathogen or bits of that pathogen and present it to the rest of the immune system. So antigen presenting cells. They take it on board and present it. So these dendritic cells have taken on board this pathogen.

They've gone into the lymphatics. They've drained all the way along the lymphatics until they meet a lymph node. Obviously that is not to scale.

They're a size of a kidney bean and things. There's no small, not like that. So it's come along and as it goes through the lymph node the antigen presenting cells are presenting that pathogen to the lymphocytes within that lymph node.

So it's an ideal environment for T cells and B cells to meet the antigen, to meet that foreign substance. We then get enlargement lymphadenopathy.

Now there are two different causes of lymphadenopathy. The most common cause for an enlarged lymph node is an infection.

An infection. And if you've got an enlarged lymph node that's enlarged because of an infection it tends to be tender. So when you have tonsillitis and you prod and poke it usually is a little bit sore for that prodding and poking. The lymph node might be local.

So if you've got an infection in your teeth, say one of your teeth on the right hand side, chances are it's going to enlarge a lymph node on the right hand side. Not necessarily the left.

So we tend to get it localized. If you've got an infection coming up through the hand you'll probably get enlargement on that right hand side. You're not going to get enlargement on the left.

So it tends to be localized close to the site of infection. Alternatively, you could have systemic lymphadenopathy.

So we see lymphadenopathy and large lymph nodes in multiple places.

That can be because of a more widespread infection, something that's got around the body a bit more. Or it could be caused by something like lymphoma. So lymphoma is a cancer of the lymph nodes. When we have a lymphoma and that causes lymphadenopathy it tends to cause an enlarged lymph node but it's not so tender. So when you prod and poke it, it doesn't hurt so much. So a tender lymph node tends to be an infection, non-tender, a bit more nasty and sinister to be looked at more closely. We'll be looking at lymphoma and leukemia in week three.

We'll look at those in week Okay, so what's going on in this lymph node then? The antigen or antigen-presenting cells arrive at the lymph node. They present the antigen to the T helper cells in the paracortex.

The T helper cells activate the B cells in those primary follicles. When the B cells become activated it converts a primary follicle to a secondary follicle. So a secondary follicle has got activated B cells in it.

That contains a germinal center which means reproducing B cells and the B cells multiply up and mature into plasma cells. Plasma cells are antibody factories.

They are going to produce loads and loads and loads of antibodies. So we have our T helpers which activate the B cells in the primary follicle to make a secondary follicle that is now going to be an antibody factory.

Releasing antibodies that then can be released to go off around the rest of the lymphatics and then into normal circulation, venous circulation, or can act in situ in the lymph node.

And then macrophages helping to clear up the aftermath or the debris.

True or false? Four liters of lymph is filtered through the lymph nodes every day before returning to circulation. Yep, tonsillitis typically causes lymphadenopathy of the pericranial lymph nodes.

False. It was the cervical ones for tonsillitis. Teeth would be pericranial.

Cut to the hand may result in lymphadenopathy to the axillary lymph nodes.

Yeah. Oh, why have I put true or false? There are five or so different lymph nodes in the axilla. Some of them drain the hands, some of them drain the breast.

So yes, true because a cut to the hand could cause lymphadenopathy in some of the axillary ones but not all of them. Okay, close enough.

Okay, 30 seconds or I'll lose you. 30 seconds and then we'll carry on. So of secondary lymphoid organ then.

So we're going to be moving on to the tonsils and payers patches. These are all types of MALT. MALT stands for mucosal associated lymphoid tissue.

Mucosal associated lymphoid tissue. This is the lymphoid tissue that supports the mucous membranes.

So we have a huge surface area of mucous membranes in the body. The linings for the lungs and the respiratory tract, the linings for the digestive tract, the genital urinary tract.

These are all risk areas for infections getting into the body. They're vulnerable areas. So we need a really good strong immune system here. And we can divide MALT up into NALT.

NALT is our nasopharyngeal associated lymphoid tissue, BALT, bronchus associated, GALT, gut associated and then GT, genital tract associated lymphoid tissue. So we've got little groups but they all work in pretty much the same way. So as long as we understand the principles, they're all going to be pretty similar.

Functionally very important, contain more antibody producing plasma cells than the spleen, the lymph nodes and the bone marrow combined.

So much of the immune system is actually found in this MALT tissue. And to be honest, most of it is in the gut.

So let's start then an overview. Just like lymph nodes, MALT contains primary follicles which remember contain unactivated B cells.

And when they get activated, they become secondary follicles.

And those B cells in the secondary follicles, those activated B cells mature into plasma cells, antibody factories and release antibodies to protect you.

The type of antibody that MALT produces is IgA.

So there are different classes of antibody.

You've got whole lectures on antibodies. You've got a whole hour on antibodies and then another hour on the uses and roles of antibodies. So there's a lot to learn about antibodies.

But one of the classes of antibody is IgA. These are our secretory antibodies. The first type of MALT then is our not nasopharyngeal or nasopharynx-associated lymphoid tissue. This is mostly our tonsils. And we have more than one type of tonsil.

The tonsil that you think of when you think of tonsils are your palatine tonsils. These are the ones which sit left and right, your pair of tonsils that sit left and right of your mouth. And they get swollen when you have a horrible nasty throat infection.

The other tonsils we have, we've got the adenoids. Now the adenoids, also known as the pharyngeal tonsil, is a single mass. It's not a pair, not like the palatine tonsils. It's a single mass that dangles or it sits behind the nose, between the nose and the back of the mouth. You know when you have one of those colds where you get that itch behind the back of your throat and you spend time going trying to kind of do something to vibrate and itch it. That'll be because your adenoids are inflamed. So that's what they're doing. The last one is our lingual tonsil which sits at the base of the tongue. So again another single mass that sits at the base of the tongue. So side on, you've got the adenoids, the palatine ones you can't really see on a side on one, and then the lingual tonsil.

When they become inflamed, you've got pharyngitis if your adenoids are enlarged and you've got tonsilitis if your palatine tonsils are enlarged or infected or inflamed.

So how's it all working then? It's a lymphoid tissue and it's actually got these deep crypts, so these deep gullies or crypts packed full. You should recognize these little clusters now. This is our primary follicles, unactivated B cells.

When they get activated, what are they going to do? Mature, become plasma cells, produce loads of antibody.

The little crypts can become filled up with pus and like white hard substances. Those of you who've had tonsilitis know that you get those white manky bits on your tonsils. They're soft and sitting in the crypts.

So that's naught. We then got gold.

The gold is mostly made up of payers patches. Gold contains 70 percent of the body's immune cells or immunocytes.

Gold can consist of both isolated follicles and also aggregated lymphoid follicles.

Aggregated lymphoid follicles are also known as payers patches and that's what we're going to look more closely at, payers patches. So here is a picture of some payers patches.

So they're aggregates or clumps of lymphoid follicles.

Here is our payers patch in the cartoon. So it's a group of lymphoid follicles and what they look like if you've put a camera into the digestive system and we look from the inside of your digestive system, so from an endoscopy, you can see these nodules.

So these are payers patches.

They're oval, irregularly distributed around the gut.

They're on the anti mesenteric sites.

In other words, they're just under the lining of your lumen in close contact where the food is going to be passing. The food's going to be passing down this hole here and most of them form a ring at the distal end of the small intestine. So at the far end of your small intestine before it meets your large intestine, that's where we get this ring of these follicles.

In other words, we're trying to stop any pathogens from getting further along. We're trying to stop them up here. If they get a bit further, we're trying to stop them with stomach acid. If they get further, we're trying to stop them getting too far. If we look at the actual structure then, what we need is a way of taking in pathogens or antigens into the body to raise an immune response and then release the antibodies back out into the gut to try and kill off the pathogen. So to do that, you should recognize the structure of the small intestine here as your villi and on the surface of the villi you've got microvilli.

But notice down at the bottom here we've got some cells without villi, without the microvilli. These are called M cells, microfold cells, and it's the microfold cells that can endocytose and take in bits of pathogen or the pathogens themselves. They then send the bits that they endocytosed through the laminar propria, the next layer that contains lots of B cells, plasma cells, T helper cells, macrophages, and onto the payers patch.

The payers patch sits in the submucosal layer, the submucosal layer.

So payers patches, groups of lymphoid follicles, groups of follicles. So M cells, laminar propria, submucosal layer containing the payers patches. Here's what's happening then.

So we've got, here's an antigen.

The M cells have endocytosed it, fed it on down to our lymphoid follicle containing our unactivated B cells. They become activated, produce or mature into plasma cells.

Plasma cells are antibody factories, so they release the antibody back into the gut. Remember this is where all your food and nutrition is out here. That's where the pathogen is, is along with all your food. So we release the antibody back into the lumen of the gut to try and target that pathogen there. The type of antibody is IgA.

This is our secretory antibody. We'll learn more about those later. Happy with payers patches.

Seeing the pattern, follicles, unactivated B cells become activated, plasma cells, antibodies.

It's quite a common pattern we're seeing. Last one then of these, and then we'll probably take a break, vault is protecting our lungs and it's exactly the same idea. Clusters of lymphoid follicles, depending on the mucous membranes of the lungs, lymph epithelium, so the aligning of the lungs, sample matter from the respiratory tract.

B cells get activated, produce antibody that gets released back into the respiratory tract to try and get rid of the pathogen there. Before it gets into your actual blood supply and the blood internal bit, we're trying to get it whilst it's in those inside out areas, bits which are connected to the wider world. Interestingly with vaults though, theoretically, you and I shouldn't have much vaults.

Vaults is only present in children and adolescents with adults only having any notable amount of vaults if you have a chronic inflammatory condition. So it seems to be something as the immune system matures and then once we've matured our immune system, we don't have so much of it.

True or false? The adenoids are a pair of lymphoid tissue found in the nose.

So that was a false, it's a single mass found in the nasopharynx. You have more antibody producing cells in vaults than in the spleen and lymph nodes combined. That one's true.

Palatine tonsils are on the left and right of the oropharynx. True.

Good stuff. We've got the spleen to go but I suggest we take a 10-minute break now so I'll pause the recording. We'll carry on with that and then we'll move on to the second topic. Okay, so I'll pause.

There we go. Okay, so just to finish off for this first part, we've got our final bit of the secondary lymphoid organs, which is the spleen.

So the spleen has several main functions.

Its first function is to filter old or damaged blood cells.

Old or damaged blood cells.

So remember, lymph nodes were filtering lymph.

The spleen is filtering blood. So slightly different things, lymph nodes filtering lymph, spleen filtering blood.

And then within it, we've got phagocytes, which are going to phagocytose any old or damaged blood cells. The spleen also has a really important role in the immune response to some pathogens, particularly encapsulated bacteria.

So the spleen is important in some bacterial infections. The spleen is a site of storage of blood cells.

It stores about 5% of your red cells, about 50% of the neutrophils.

So half of your neutrophils are stored in your spleen. Remember, neutrophils play a really important role in bacterial infections. And about 30% of your platelets.

30% of your platelets. As we'll see in a little bit, the spleen is a site of blood cell production when you are a fetus. When you're developing in utero, it's the spleen and the liver that produce your blood cells, not the bone marrow. So as we get older, that switches off, but we can reactivate it.

We can switch the spleen back on as a site of blood cell production.

So extra medullary means outside of the bone marrow, extra medullary, hermatopoiesis.

Clinical relevance then to all of this. People do rupture their spleen. If you're involved in a car crash, an RTA, something like that, you might get rupture of the spleen. Now, if the spleen is storing loads and loads of blood, rupturing your spleen is clearly a huge dangerous thing because you can lose a vast amount of blood very quickly. So that's very, very dangerous.

Splenomegaly as an enlarged spleen.

If we get an enlarged spleen, we'll start to store more and more blood cells in it.

So it means our circulating blood cells are reduced.

We've not got as many circulating around because they're all sitting inside the spleen. Some people have their spleen removed, particularly if they ruptured it, they might be taken straight into surgery, have it removed. Now you can live without a spleen quite happily, but you're not going to be doing so much of the filtering. You're not going to be quite so good at fighting off bacterial infections and you've not got so much of a store of blood cells, but you can live pretty well.

The spleen itself is an ovoid organ in the upper left abdominal cavity. So it's below the diaphragm, it's in the abdominal cavity. We can see here, it's got a smooth surface that kind of fits in around the inside of like the rib cage.

But then we've got these various different indentations and notches where it's resting against other structures in the abdomen. So in contact with things like the stomach, the splenic flexure of the colon, not the left kidney, the left kidney and the tail of the pancreas. So all of these different indents will be where other organs are touching it.

A healthy spleen should be about this size on the picture, the dark purple. And if we wanted to palpate the spleen, you can try and get your fingers onto it under the rib cage. If it's a healthy size, you can't get your fingers onto it.

But if it becomes enlarged, so if it starts to become enlarged, now you can get your fingers onto it under the ribs. So if when you do an abdominal examination, you can feel the spleen, that tells you it must be enlarged. If you can get your fingers on spleen, it's an enlarged spleen, to be able to be feeling it.

Its structure, when we look at it, it's got an outer capsule and that has projections coming into it called trabeculae.

So we've got these trabeculae here and they form like compartments.

They form compartments within the spleen. We've got an area called the hilum.

Do you remember the hilum from both lungs and kidneys? It was where all the structures went in and out. Do you remember the kidneys? We had all the arteries and veins went in and out of that one spot. The lungs, we've got the bronchi, and their vessels go in and out of that one spot.

That's the hilum. Same for the spleen. We've got the splenic vein and we've got the splenic artery going in and out. If we look at the tissue inside it, we can see it's made up of red pulp and white pulp. Red pulp, we've got the splenic sinuses. We'll look at those in a bit more in a moment.

We've got their blind-ended vessels. You can see that they're ending in dead ends, blind-ended veins, and there's a little window, a three micrometer window or filter between them.

So this is where the cells have to squeeze between a small gap to be able to carry on circulating.

The white pulp is where we've got loads and loads of lymphocytes and macrophages. This is doing the immunological screening. So we've got filtering out old and knackered blood cells and we've got looking for any signs of infection. Blood's going to come into the spleen through the splenic artery. So it comes in the splenic artery. They then divide into arterioles and then from there it goes into this open blood system. It's unlike most other parts of the body.

The red cells are going to rush along right to the very ends and go straight into the red pulp, whereas the slower white blood cells will migrate out into the white pulp.

So we've got blood passes through the white pulp, into the red pulp, and then it reenters into these splenic sinuses and then goes down by the splenic vein back into normal circulation.

Trauma, bleeding air. You don't want to rupture it if you can help it. So fast-moving red cells will go straight down the arterioles, flowing straight into the red pulp, and then drain back into the splenic sinuses.

Between those splenic cords and splenic sinuses we've got these three micrometer windows and the red cells have got to be able to squeeze through that three micrometer hole. How big is a red cell?

How many micrometers? Can you remember? It's about seven, seven micrometers.

So to be able to get through a three micrometer hole, it's got to squeeze and come out the other side. I know this is a bit mean, I'm so bad.

I always picture this like a little assault course. You and I, well you, could fit through a little hole and get around the assault course, you'll be fine. Granny can't get around the assault course, can't squeeze through the hole, so she's out.

She is destroyed and recycled.

I know it's a bit mean, but that's how I remember it.

It might help you remember it as well. Okay, so any red cells that can't get through that window, that little hole, they are gone.

They're going to be phagocytosed by macrophages and their components broken down and recycled. When they get broken down the iron gets recycled, it goes off to the bone marrow to new red cells.

The bilirubin is transported to the liver and then it gets processed and excreted. Clinical trauma breathing area.

What happens to the white cells in the plasma then? They're traveling along the blood vessels much more slowly. They tend to kind of roll along surfaces. They're going to come out into the white pulp and the white pulp, here's our label for white pulp here. We can see, we recognize this pattern here. This is a primary follicle. What is a primary follicle?

It's unactivated B cells. So we're screening. Have any of the white blood cells in the plasma? Is there any antigens? Do we need to activate these B cells at all? Next to the arterioles, we've got this tissue called periarteriola lymphoid sheath. The pals tissue, periarteriola lymphoid sheath. There's loads of T cells in there. And then in the marginal zones, we've got the macrophages helping clear up all the debris, any mess that's left behind.

Splenectomy, small risk or increased risk of bacterial infections over the rest of us because the spleen has such a role in bacterial responses to bacterial infections and storing neutrophils.

Storage of red cells, neutrophils, platelets, sympathetic stimulation. Oh, I love this one.

Not last year, but the year before, Lucy, some of you might know Lucy, she managed to track down this video for me. I've known about it for years. It was from, I don't know, 2014, something like that was on telly. Professor Alice Roberts, she did a fantastic experiment.

She took a blood, not she, she got a friend to take a blood sample, measure the blood cells, and then she climbed all the way up to the top of, I thought it was a church, but I think it's not, it's a big theater. And she abseils down the center of this theater, and then they take another blood sample. And what happens is a lot of her blood counts have gone up because her body has perceived threat.

It's perceived that she might have a big trauma. So therefore she might need lots more red cells because if she loses loads on the floor, she might need more. She perceives she might be at risk of infection. If she breaks her leg and has an open fracture, she perceives subconsciously her body perceives she might need more white cells. Her body perceives it might need more platelets in case she bleeds. So it releases all these blood cells probably from the splenic stores.

So it's a fantastic video. We won't watch it now because we haven't got much time, but it's one I'd recommend watching.

And Lucy did amazing to track it down because I couldn't find it for years I was searching.

Okay, so threats, just threats of potential trauma can change our blood counts. The last function of the spleen then is extramedullary hematopoiesis.

So this is the idea that normally in our embryonic state or fetal state, our liver and our spleen contain stem cells for blood cell production.

And then what happens is as we mature, they then stop producing them. So we should switch them all off. So as we get older, those stem cells migrate to the bone marrow and this is where we produce our blood cells.

But if this gets broken, if your bone marrow is broken, we can reactivate our splenic and liver abilities to produce blood cells.

So we get a pathologic response.

So adult hepatic marrow is broken.

In other words, probably leukemia or another cancer of the bone marrow. So leukemia and it's going to cause hepato megalis, splenomegalis, they're going to become enlarged because they're having to do a bigger job than normal.

Okay, true or false? You have more antibody producing cells in malts than the spleen? We've probably done that one before, haven't we? The answer is true.

You can survive without a spleen but you have an increased risk of developing viral infections.

False, it's an increased risk of bacterial infections.

Primary lymphoid follicles contain unactivated B cells and require activation before differentiating into plasma cells and producing antibody.

True. Okay, that's a summary of what we've covered. There's your self-study.

So there's ideas of things to look at if you found the material challenging.

Some papers if you found it easy peasy and of course everybody needs to go through the notes to get yourself exam ready.

There's your QR code for this one and then we'll give it one minute whilst I set up the powerpoint and we've got the second lecture.

Okay, so scan yourselves in at this stage and then we'll tak