36: gingiva i

Transcribed by Jazmin Lui May 6, 2014

CRANIOFACIAL BIOLOGY – PERIODONTAL TISSUES: GINGIVAL EPITHELIUM AND CONNECTIVE TISSUE I – DR. CRAIG

1. Craniofacial Biology: Periodontal tissues: Gingival epithelium and connective tissue

[Loud feedback] Oh wow. Maybe I can’t move. Which is a problem. This is weird. Because if I can’t move around this is difficult for me. Maybe I can get some help. Certain people have certain styles you know when they present stuff, if I have to stand behind a podium it’s like death to me. So we’ll do the best we can. So let’s recap. We had lectures on development of PDL tissues, that’s not only important for your basic understanding of teeth, but more importantly for us as clinicians is the last 20 years or so people have been really focused in, surgical specialties especially, and dentistry is basically a surgical speciality, really focused in on…yeah I’m getting some weird stuff happening here…what do I have to do here, change my voice? People really, in surgical specialities have been really focused in on…thank you very much, is that alright? More importantly I can move around. Now I’m a happy guy. And more importantly folks in surgical specialties have really been interested in how their tissue of interest develops because the idea is: if I really understand cellular molecular biology of how that tissue develops, maybe if I go into surgery to restore lost parts for a patient I can actually recreate some of those events that occur during development and radically alter the outcome of wound healing for therapeutic gains. I think, my perception is different than yours, I think we had an unbelievable example yesterday where the understanding of how periodontal tissues develop actually allows folks, under certain conditions, it doesn’t happen all the time, allows clinicians to actually regenerate cementum, PDL, and alveolar bone that has been lost to an infectious product/infectious immunological process, periodontitis. And that’s been like a holy grail of surgical specialties. It’s one thing to remove pathology and and try to create a new homeostasis in a tissue, it usually results in scarring. You don’t have the anatomy back, you may not have the function. But if you can get regeneration, not only can you get anatomy back, you can get function back. It really makes me proud, perio, is one of the first clinical disciplines first to do that. We’re going to have a whole session this week on periodontal regeneration, we’re going to revisit that perhaps from a different perspective so I can hammer home those ideas cause those are really powerful. So you go into your practice and you tell Mrs. Jones, gee there’s an infrabony defect and that tooth is loose, but I’ve got a shot at actually regenerating lost periodontal tissue connection apparatus, that’s a powerful thing for a patient. We talked a little bit about development of periodontal tissue connection


apparatus, and now we’re going to switch gears a little bit and talk about gingiva, which is the fourth component of periodontal tissues and remember gingiva doesn’t participate in those epithelial mesenchymal interactions that characterize odontogenesis. However if you understand the biology that’s going at the cellular molecular level you can do seemingly miraculous things for the tissues. Let’s talk about periodontal tissues. So what are the components of the gingiva?

2. Components of the gingiva

You can characterize the gingival into these four categories. Oral or gingival epithelium, that’s covering the alveolus, when you look in clinically that’s what you see. Sulcular epithelium, as you go around into the sulcus that’s the epithelium that’s lining the sulcus. The other side of the sulcus will be the tooth surface. Junctional epithelium, gingival connective tissue. Oral gingival epithelium is keratinized or parakeratinized and it’s a stratified squamous epithelium. The keratin is really important, because the keratin is like really thick, it’s a thick protein, rather, very good for abrasion resistance. But perhaps most importantly, keratinization as we know today, really impedes the penetration of water and any products dissolved in water, in aqueous solution. It impedes them from penetrating deep into connective tissue. As it turns out the inflammatory state of the connective tissue is real important. Sulcular epithelium, so now we’re going to go around the corner into the sulcus, we’re going to climb into the sulcus. This epithelium can be non-keratinized or parakeratinized depending upon the inflammatory state of the underlying connective tissue. You as therapists can modify the state of keratinization if you get your patients to practice really great oral hygiene. As we go more apical in the periodontal sulcus we go against this magical epithelium that adheres onto tooth surface, junctional epithelium, that’s always non-keratinized, it’s a stratified squamous epithelium. One side attaches to the tooth or tooth analog, and the other side attaches to the underlying gingival connective tissue. Yes? [Student: is it more keratin with inflammation?] oh, just the opposite. What happens to epithelium when it’s in an inflammatory area, especially in the mouth, it goes through mitosis much faster. As it’s going through mitosis much faster it doesn’t have time to express the genes associated with keratin. So you’ll see this over and over again. You want to try to get the inflammatory state as low as possible for your surgical patients. If you don’t you’ll start having this hypertrophy of epithelium in the area that’s not keratinized which allows the penetration of bacterial products deeper into the connective tissue, further fuelling the inflammation and things get kind of out of hand. We’ll talk about that more, we’ll talk about inflammation, general pathology, and I think I gave you some lectures on pathogenesis of periodontal tissues. Where


was I? You destroyed my chain of thought. Underlying gingival connective tissue. So underlying connective tissue, in Tony Nanci’s book, Tan Catte’s oral histology, he divides it into deep and superficial connective tissue. we’re not going to do that for our purposes. We’re just going to talk about gingival connective tissue as gingival connective tissue.

3. Components of the gingiva (oral (gingival) epithelium…)Here’s some histology from one of my teachers. He probably did the

best oral histology I know if. His name is Max Litzgarden. He was the chair of perio at University of Pennsylvania and a few other things. And Max did these beautiful histological sections, and we’ll talk about them as we go along. This is human and I’ll tell you how, living human, and I’ll tell you how you got these. You probably can’t do these any longer so that’s why I showed them. Here’s the oral surface up here, right? [points to dark strip on right] so here’s the oral or gingival epithelium, and this deeply purple layer is the squamous cell layer and this is all keratin out here. A really good barrier for penetration of bacteria and bacterial products in the underlying connective tissue. Then as we go along the sulcus here all of a sudden this purple stuff, this is sulcular epithelium [points to left side of tissue, white triangle] this is pretty healthy gingiva because I don’t see any inflammatory infiltrate down here in the connective tissue. Notice you have vessels down here but no vessels up here. Epithelium doesn’t have any vasculature. So it depends on diffusion across basement membrane for its nutrient and waste exchange. You don’t see it on this slide but further down is sulcular epithelium. This is a really nice histological section of gingival connective tissue.

4. Components of the gingiva (oral (gingival) epithelium…)

So this I lifted from the Tan Catte book and it bothered me. And I couldn’t put my finger on it for the longest time but now I think I know what’s going on. In my opinion there’s some problems with the Tan Catte illustration although artistically it’s beautiful. So here’s the cartoon and here’s actual histology. So here’s the marginal epithelium, so this is, when you look in this is the most coronal extent of the gingival tissue, they call it the gingival crest, I have no idea why they call it the gingival crest, marginal epithelium is what most people talk about. And this portion, here’s the sulcular epithelium and here’s kind of like sulcular epithelium here. This is not attached to tooth surface in this case, enamel, and since this is not attached sometimes this is called free gingiva. And the gingiva that’s further down that’s firmly attached to tooth or bone this is called attached gingiva. And when you get your lectures on periodontics, depending on if you’re talking about implants or teeth, the amount of attached gingiva can be important to


some folks. What else is here. So we have those wonderful gingival fibres that are attaching to the cementum of the root surface. These are going from the tooth out to the gingiva – the dentogingival fibres that we talked about yesterday. And here are some, going from the tooth to the periosteum, dentoperiosteal fibres. And here’s some fibres of the principal fibres of the connective tissue proper, so these are the [points to very bottom] crest fibres, horizontal fibres. And now I’m looking at this cartoon stuff here, and I don’t know what this stuff is [points to purple fibres joining the junctional epithlium to tooth]. Maybe this is cementum here but it’s the same colour as these fibres, that sort of bothers me but that’s alright. You can have cementum overlaying the enamel surface. But when I go over here, the other thing I’m supposed to tell you, here’s the crest [points to alveolar crest] mind you, in primates, you need to have about 2 mm cementum exposed so you can have attachment of the gingival fibres or at least 3 of the gingival fibres, 3 of the 5 gingival fibres. Now I go over here and I have a problem. Here’s the osseus crest and here’s the CEJ, and I can believe this is epithelium, but there’s a lot of epithelium here [points to junctional epithelium region on histological section] and what characterizes the junctional epithelium is that one of its basement membranes, the so called external basement membrane is somewhat linear, and then when you are getting up at sulcular epithelium it becomes more, you start to see rete pegs. But you don’t really see this much here until you get way up here. And the bone is coronal to the CEJ, so this is a violation of biologic width. I’m looking at this and saying, this is weird! I look up here and look at these rete pegs. They don’t look like the human tissue that I’ve been showing you. I think this is dog. Because canines, carnivores, will have osseus crest that’s coronal to the CEJ. I think Nanci stuck in dog histology here. So when you look at this make believe osseus crest is down here, unless you’re going into veterinary dentistry you’re probably going to dealing with mostly humans and not dogs. So I think we covered that. So you kind of have an idea of where these structures are in space.

5. Formation of the dentinogingival junctionDevelopment of the dentogingival junction. When crown formation

ends, the enamel organ that formed the tooth regresses into something called the reduced enamel epithelium. It has basically has two layers. It has the inner layer which hosts the ameloblasts and they attach to enamel surface by hemidesmosomes. Epithelium attaches to substrates with hemidesmosomes. And then there’s another layer, the OEE, the collapsed stellate reticulum, the striate intermedium, that’s all been collapsed into the outer layer of the reduced enamel epithelium. And we’re going to have a lecture on tooth eruption. So as this tooth begins to erupt into the oral cavity, slowly it comes into contact with the overlying oral epithelium, there’s a number of


cytokines released especially from the outer reduced enamel epithelium, also there is ingress of bacterial products and antigens, from the oral cavity into the sight, so inflammatory mediators like prostaglandins, and those kinds of things start to be elaborated, and you‘ll learn more about inflammation in general pathology. But just like the question over here, when you start to have inflammation start to occur, what happens? Epithelium starts to proliferate. So that’s kind of neat. So this outer reduced enamel epithelium starts to proliferate can you see how it’s getting thicker here, if we had a higher power image of this area here we’d see it’s inflamed with inflammatory cells. And we have this thick layer of overlying outer oral epithelium and the two meet. And the idea is if you want, I think, thinking histologically, you want to have an epithelial lined eruption cuff through the tooth can erupt into oral cavity. So you don’t have open connective tissue that allows for infection and ingress of bacterial antigens. How many of you have kids here? Well you’ll realize this idea doesn’t work very well. There’s a phenomenon called teething. Children can be nasty individuals, or at least some of them, when they start to have teeth erupt into the oral cavity, because these areas may become infected or may become inflamed, they’re not very comfortable little campers at that point in time. The idea is to have an epithelial lined eruption cuff through which the tooth can erupt into the oral cavity. So let’s take this a little further.

6. Formation of the dentinogingival junction (after amelogenesis…)Again this is all human. Notice how this doesn’t look like the Tan

Catte picture at all? It looks really like canine material. So anyways, now this tooth is erupting further into the oral cavity. So here’s the overlying oral epithelium. There’s some epithelium here that lines this developing sulcus. If you had maybe a periodontal probe you’d be able to put the probably all the way somewhere down here, I guess, very easily. So this epithelium is not attached to enamel surface. It lines the sulcus, so we call it sulcular epithelium. Notice how we really developed over here on the oral epithelium. And you still have developed rete pegs all the way down to about here [points to junctional epithelium] and then right about here all of a sudden the rete pegs tend to go away and you have a more linear interface between the junctional epithelium and the underlying connective tissue. So on histological sections you can always tell where junctional epithelium begins. And just like the book says, tissue that Max got, junctional epithelium goes all the way down to CEJ. All the way down to the CEJ. So this junctional epithelium initially derived from reduced enamel epithelium. And there were two very famous periodontal scientist types. One was called Bearhog. I love that name. I’d love a name like Bearhog. He stated that this initial adherance of the junctional epithelium to the crown of the tooth, the enamel of the


tooth, is called the primary epithelial attachment. Primary epithelial attachment. And the sulcular epithelium derived from oral epithelium but the junctional epithelium is derived from reduced enamel epithelium, initially that’s called the primary epithelial attachment. As time goes by these epithelial cells tend to migrate into the sulcus and they’re lost, they’re desquamated. And stem cells that are present in this area give rise throughout life to another succeeding generation of junctional epithelial cells and those cells or that attachment is called the secondary epithelial attachment. Ok so, the initial one is from reduced enamel epithelium as the tooth erupts, as life goes on those epithelial cells are replaced by stem cells in the basement membrane and that becomes the secondary epithelial attachment. Why do they talk about the primary and secondary epithelial attachment? I have no idea. One of those things you’ve got to know. Now let’s see if we can go further on this.

7. Formation of the dentinogingival junction (after amelogenesis…)Kind of focus in on this junctional epithelial attachment. So here’s the

sulcular epithelium, notice the convoluted basement membrane or basement cell layers. And then you start to get around here and it sort of levels out. And this is a very unusual epithelium because I can’t think of another epithelium that does this in the body. When you think of the gastrointestinal tract, and I find myself thinking about my gastrointestinal tract quite often during the day, and I can’t think of another place in the gastrointestinal tract where you have this structure, this hard structure, this non desquamating structure that starts deep in connective tissue, pierces through the mucosa and is sitting in one of the filthiest spots of the body, the oral cavity. Teeth are kind of unusual if you think about it. It gets colonized with this biofilm. Some of the bacteria that can be in this biofilm is really nasty bacteria. So this junctional epithelium serves an incredible purpose. Not only by hemidesmosomes attaches to tooth surface, but because of its length and continuity it impedes, it’s not keratinized, it impedes the ingress of bacterial products into deep underlying connective tissue in health when its doing its job. If It doesn’t do it’s job you’ll have gingivitis and if you’re susceptible you’ll get destruction of the periodontal connective tissue attachment apparatus, which is way down here somewhere, and you start progressing into periodontits. So this interesting thing about the junctional epithelium is if you want to talk histologically there’s 2 basal lamina. So the part that attaches tooth is called the internal basal lamina, the conventional basement membrane that unites the epithelium with the underlying connective tissue is the external basal lamina.

8. Oral epithelium


Let’s talk a little bit about oral epithelium. You’ve had lectures on epithelium, I’m going to concentrate on things more specific to oral gingival epithelium. It’s a stratified squamous epithelium, keratinized, ortho or para-keratinized. Consists of a basal layer, a spinal cell layer, a granular cell layer and a squamous or sometimes called cornified cell layer. And let’s go through each cause they’re kind of important.

9. Cytokeratins expressed in periodontal tissuesIf you look at, if you want to characterize epithelial cells, and this

came directly out of cancer therapy, you can characterize how primitive a carcinoma is depending on what cytoskeletal elements in expresses. Cytokeratins. Oral gingival epithelium is very differentiated epithelium, this is the constellation of cytokeratins it expresses, junctional epithelium, reduced enamel epithelium, our friends the cell rests of Malassez, these are all simple epithelium, relatively primitive epithelium, and all you really gotta remember is that they express cytokeratin 19. So relatively primitive epithelium for those three types. Oral gingival epithelium, highly differentiated. A typical stratified squamous epithelium.

10. Oral epithelium: basal cell layerSo this is some incredible histology from Max. And let’s talk a little bit about the basal cell layer. Not only is the basal cell layer convoluted, but the processes of the cells are convoluted [points to white/purple squiggly border]. Not only is there no vasculature in the epithelium, all vasculature comes from underlying gingival connective tissue. Here’s a red blood cell cross section. Unbelievable histology. You won’t see histology like this very often. So let’s talk about basal cell layer. The big old basal cells that are sitting out here.

11. Basal cell layer (compartments)Sitting on the basement membrane are 3, actually 3 different types

of keratinocytes. And you can kind of differentiate them by the types of integrins or cell adhesions molecules they express. In basal cell layer there are stem cells and they remain firmly tethered to underlying basement membrane because of the 3 integrins expressed, and these are the ligands, you don’t have to remember this stuff. The stem cell under appropriate conditions will go through mitosis, and the daughter cells can either remain stem cells, but more likely they go into this compartment, this transit-amplifying cell. These cells can still retain the ability to divide, though diminished, but they’re thought because there’s down regulation of these integrins. What’s beginning to happen is these transit-amplifying cell are beginning to lose contact or their affinity for attachment to underlying basement membrane. And the third compartment you can kind of see in the basal cell layer are committed cells. They have stopped expressing the integrins


completely, and like a balloon that’s being lost into the atmosphere, begins to migrate off basement membrane and go into the spinous cell layer and start turning on genes appropriate to spinous cell layer.

11. Basal cell layer (electron micrograph)So here’s an electron micrograph. And here’s a portion of a

keratinocyte sitting on the basement membrane. Here’s the underlying gingival connective tissue [points to light tissue beneath basement membrane] and if you’re a histologist you’ll be saying to yourself “Boy there’s a lot of complexity here, I know these things, these are mitochondria right? [points to round cells in upper half of slide] These things in here, these are cytoskeleton right?” and I’m going to call these tonofilaments. Why? Because I like the name. I have no idea chemically what these things are or what they do. I kind of noticed down here in the basement membrane there seems to be different layers. This layer seems to look electron dense, well call it the lamina densa [dark grey], and this layer looks electron luscent, so I’ll call it lamina lucida [light layer], still have no freaking idea what these things are or what they do, and then I see these little things come out, sort of like fingers of Velcro [extend down from lamina densa], and I’m sort of imagining in my mind because I know that all of these things are collagen fibrils, and are cut in crossection, and it looks like these guys are sort of going around the collagen, like vicromesh. So I’m going to call them anchoring fibrils. And then I noticed that the cell membrane is not uniform. In certain areas its denser (dark black patches) so I’m going to call this a hemidesmosome. And I notice these tonofilaments seem to attach to these hemidesmosomes. And so I’m going to call this the internal attachment plaque and the external attachment plaque because it sounds like I know what I’m talking about. But I still have no idea what I’m looking at or what their functions are. How were these dissected out at the molecular level?


12. Basal cell layer: basement cell membrane ultrastuctureSo we’re going to go through some of this. This is a little cartoon

showing morphology. So here’s the hemidesmosome and the attachment plaque. And here’s the cell membrane of one keratinocyte. And here is this hemidesmosme with tonofilaments attaching into it. And then there’s some magic here, haha, whoever did this has no idea what they’re talking about [points to lamina lucida]. This is the lamina lucida, I have no idea what a lamina lucida is but I can point it out on a micrograph. Here’s the lamina densa. And I have these things called anchoring fibrils and fancily I have these Type I collagen fibrils are that are lacing through, kind of attaching everything. So all is good with the world but if you’d like to move ahead and push the bounds of science perhaps you want to do something else. So now we know what the proteins are. And I just want to go through one protein cause it has clinical implications in practice.


14. Bullous membrane pemphigoidYou will see folks who have this. This is a lady, this is a terrible

photograph, should get a new one. This is a lady who presented to the clinic here, the oral medicine clinic. Her gingival is really red and inflamed. If you took a 2 by 2 vase and put it there and rubbed it really lightly, all the epithelium would come off underlying the under connective tissue. And this woman at this time is not a happy camper she is really in pain. This disease is called bullous membrane pemphigoid. Bulli is nothing more than a blister. But if you said blister to your patient they’d know exactly what you’re talking about so medicine and dentistry always try to have a different name so we can have some semblance of authority on this subject. So this is membrane pemphigoid. Now there’s a second autoimmune disease called pemphigus. You’ll learn about this when you get into general pathology. This is bullous membrane pemphigoid. If you didn’t know what you are looking at, you’re taught to take a bard parker blade, take a biopsy, let’s see what this looks like histologically. So if you did that, this is what these lesion would look like histologically.

15. Bullous membrane pemphigoid: histologySo here’s epithelium (points to dark red tissue) and here’s the

connective tissue (points to pink tissue). And these are all lymphocytic cells, B and T cells, mostly T cells. So it’s enormous, the inflammatory infiltration that’s occuring. This epithelium is beginning to lift off the connective tissue, making a blister (points to white space) or bulli. But then if you came in with an antibody with a fluorescent tag on it, and that antibody was specific for human IgG antibody, one of the five classes of human antibody. This is what you’d see under fluorescence microscopy.

16. Bullous membrane pemphigoid: immune fluorescenceYou’d see the overlying gingival epithelium (points above green) and

underlying gingival connective tissue (points under green). There’s a whole lot of this patient’s IgG antibody right at that interface of the basement membrane. So this patient is making an antibody against and antigen, some self antigen. We don’t know what it is. If I was in charge of this the story would end right here. However this a person named Elaine Fuchs who’s at the Rockefeller University just up the road, and Elaine Fuchs had, a long time ago, about 20 years ago, did the following using antigenic mice. I want to walk you through this to give a flavour of how these people unravel this stuff, there are some really clever people in the field. So all Elaine has is antibody from these patients against some protein she believes. So what does she do? She does…what happened??? I lost all my stuff! Huh, somehow, it didn’t get…that’s amazing. Ok so I’m going to have to walk you through this. So what she did, she went and she made a cDNA library. She took all


the RNA that’s being expressed and she cloned it into an expression vector. If you tell the plasma if you have the right promoter for your plasma, you can actually drive synthesis of that piece of cDNA. She has the antibody against this bolus pemphigoid antigen. So with the antibody she can pull up colonies of bacteria with recombinant. So now she has a piece of gene to the bolus pemphigoid antigen but she doesn’t know what the gene actually encodes for. So what you can do is take embryonic stem cells from mice and microinject this micro DNA into stem cells. And then you can go into a female adult mouse and induce a state of pseudo pregnancy in that mouse and implant stem cells. The mouse is going to allow development of that fertilized egg, hopefully it has your recombinant protein in it, take a little bit of the tail from the littermates and look for the mutated protein, so you’re going to knock out that bullous pemphigoid antigen so you can get heterozygote, and then you’re going to do some incest here, you take littermates that are heterozygotes and mate them together. You can imagine all this stuff that comes with trying to mate these poor animals. And you can actually come up with animal that has both the genes knocked out. And if you do that,

[switches to slide 12 basal cell layer cartoon)

If you do that, and you look, well first off, if you look at the mouths of these little recombinant mice that had the bullous pemphigoid gene knocked out, what you don’t see is you don’t see this structure (points to lamina lucida unit). As it turns out, this structure in here happens to be a collagen, it’s type 17 collagen. And that’s the antigen that people with bullous pemphigoid antigen make antibody against. Antibodies gets decorated around this structure, this brings about an immune response, this area is destroyed, if it’s destroyed then underlying epithelium lifts away from the connective tissue giving these blisters. One of antigens which turns out to be the internal plate which is collagen 17. And in your text, it should’ve been, I don’t know what happened to this in the hand out. I have this in the hand out. Just a second. I hate making a mistake because I never make mistakes. I thought I made a mistake once but I was wrong. Ah! I see it. I see the mistake. Watch this is going to be much better. I’m feeling better already.

[Opens new powerpoint]

17. Bullous membrane pemphigoid (bullous pemphigoid antigen knockout)

Life is good. So basically this is what the Fuch’s lab did. And those of you that are kind of into recombinant DNA technology can look through this.


18. Bullous membrane pemphigoid (DNA blots)Now this is what I wanted to show you, this is so neat. So this is

panel A, this is panel B. So a southern blot of what happened here. 6.7 So this is the bullous pemphigoid antigen (points to 6.7), and what they did was transfected a gene that had that gene knocked out, so it’s smaller (points to 2.6). So they put it into a pseudo pregnant mouse, they looked at the littermates. Unfortunately I watched them do this in Nick Partridge’s lab, and they do this without anaesthesia, they take a bit of the tail and then, just like that. You can tell how many times they do this because the tail gets shorter and shorter and shorter. So here is a mouse that didn’t get knocked out gene (+/+) and here’s a mouse that did get a knocked out gene (+/-), that’s intact and one’s knocked out, and then they get these two guys together, hopefully one’s male and one’s female and they have a night of incestuous love, and the littermates if you’re lucky and the live, come out as the homozygous transgenic animal (-/-). This is a RNA northern blot (D). So here is the intact animal, has both alleles that are intact. Here is the heterozygote, I love this, so the RNA is half (+/-), I love this, you never see this. So this is the homozygous, both alleles knocked out, nothing. And when you look at (E), here’s the protein, the homozygous, the one that’s completely knocked out is missing. So you look to see what’s happening. They have the blistering just like the human phenotype

19. Bullous membrane pemphigoid (panel legeds)Here histology is not as good as Max’s but she’s going to get a Nobel

prize, so who’s the greater fool? So up here we can see, here’s the lamina densa, lamina lucida (LD, LL) here’s the hemisdesmosomes, here’s the hemidesmosomes. High power here, and here are these cytokeratin or tonofilament (inset top right box) coming in and attaching. And in the guy that’s knocked out, the transgenic knockout you don’t have that internal plaque (inset bottom box). So it turns out when you biochemically characterize that gene it turns out to be collagen 17. And – YES!

20. Basal cell layer: BPAG1 is COL XVIIHere’s the diagram. Here’s the old diagram, here’s kind of like the

new diagram. In the so called tonofilaments here is the cytokeratins, and here are these desmosomes. Turns out to be these anchoring fibres right here, that’s collagen VII, you gotta remember that. It was discovered by Bob Burgenson, almost worked for Bob Burgenson. And here’s the underlying type I collagen. And right in here is collagen XVII and it’s forming a sort of an attachment into the hemidesmosome and into the lamina densa. The lamina densa has a lot of type IV collagen. And these laminens and stuff they tend to populate the lamina lucida. Through these kinds of molecular workings people have begun to


decipher out their actual biological chemical component and their functions for a diagram like this. So when you get into oral medicine and they start talking about bolus pemphigoid. Raise your hand and say “I think the antigen is type XVII collagen” just watch your professors, they’ll go nuts. They’ll say really? And that’s enough for bolus membrain pemphigoid.

21. Basal cell layer (non-keratinocytes…)What else is in the basal cell layer? We also have non-keratinocytes

in the basal cell layer. Some of which are melanocytes and in some patients can be very extreme. These are real important: Langerhan cells are dendritic cells that sit there – they can be infected with virus or pick up bits of antigen. Once they do that they change their phenotype, go into lymphatic drainage and go into lymph nodes, where they help with antigen presentation to be in T cells. You’ll learn more about this in general pathology but these are real important, these dendritic Langerhan cells. We also have Merkel cells which are a tactile sensory cell. Depending upon your state of periodontal health you’ll have various forms of lymphocytes which you’ll learn about next year, which participate with the innate and adapt immune response. Some quick pictures of melanocytes and then we’ll take a quick break.

22. Basal cell layer: melanocytesSometimes the melanin can be quite dramatic.

23. Basal cell layer: melanocytesHere’s a little diagram, so here’s a little melanocyte and the basal cells there, it has these little processes that go up in to spinous layer. What you see are these little packets of melanin and they give the dark colour in these areas. Let’s take a 5 minute break and then we can go through the next portion of the next hour.

36: gingiva i

Documents