The multifaceted virulence of adherent-invasive Escherichia coli
- Thread starter kiny
- Start date
Help Support Crohn's Disease Forum:
kiny
Well-known member
- Joined
- Apr 28, 2011
- Messages
- 3,472
To reiterate that AIEC is a feature of ileal disease, and rarely colonic.
The ileum is very different from the colon. The colon lacks M cells (peyer's patches) and paneth cells that are found at the ileum's epithelial barrier.
Ileal and colonoc crohn's are pretty different diseases. They're very different organs.
The ileum is very different from the colon. The colon lacks M cells (peyer's patches) and paneth cells that are found at the ileum's epithelial barrier.
Ileal and colonoc crohn's are pretty different diseases. They're very different organs.
Last edited:
Our GI doctor has colonic CD. Are you saying it should be categorized as a different disease?
kiny
Well-known member
- Joined
- Apr 28, 2011
- Messages
- 3,472
It was categorized as a different disease in the past. Ileal crohn's disease was called Chronic Enteritis, enteritis which refers to the small intestine, before we started to call it crohn's. Then it was made even worse by lumping UC with crohn's and using the unfortunate term IBD.
These umbrella terms hold back personalized treatments. It also confuses patients when studies lump together ileal and colonic disease. EN works very well for ileal disease, but less for colonic disease. If studies don't make these distinctions, patients won't know.
Last edited:
A friend wants me to ask you this question: her son's Crohn's is in the jejunum and she would like to know if AIEC is also the main trigger and if EEN will be just as effective in his treatment? He is only 6 years old and currently on Humira.
kiny
Well-known member
- Joined
- Apr 28, 2011
- Messages
- 3,472
It's certainly possible in the distal jejunum, where there are still peyer's patches and where M cells take up antigen. E coli and its close relative Salmonella, exploit M cells to enter tissue. But higher up the GI tract, like the proximal jejenum, there are no M cells covering peyer's patches and the environment become much more hostile for these bacteria. Bacterial load decreases rapidly as you go up the GI tract, so does the likelyhood of developing crohn's disease decrease.
Why EN might help is that people with crohn's disease often have SIBO, and bacteria are able to maintain a presence in the jejunum, likely due to delayed gastric emptying. EN is very effective in treating SIBO.
Why EN might help is that people with crohn's disease often have SIBO, and bacteria are able to maintain a presence in the jejunum, likely due to delayed gastric emptying. EN is very effective in treating SIBO.
Last edited:
kiny
Well-known member
- Joined
- Apr 28, 2011
- Messages
- 3,472
Peyer's patches and the M cells that cover them are an exclusive feature of the epithelial barrier in the small intestine and distal jejenum. The M cells are little indentations, if you search for "electron microscope m cells" on Google you will many images.
Unlike the rest of the epithelial cells, they are not covered by mucosa, they are directly exposed to lumen content.
These M cells are part of the peyer's patches and lymphoid follicles. I once posted a german study of very early crohn's disease, where the first signs of crohn's disease where small inflamed lympoid follicles.
These M cells are the entry point of bacteria and dietary antigen, below them you find a dome, a peyer's patch, it's big enough to see with the naked eye. That peyer's patch is full of T cells, B cells and macrophages, it's a dense aggregation of immune cells.
When someone develops inflammation in the small intestine, it is the peyer's patches that initiate that response, it is a response to antigen crossing the epithelial barrier through M cells.
Unlike the rest of the epithelial cells, they are not covered by mucosa, they are directly exposed to lumen content.
These M cells are part of the peyer's patches and lymphoid follicles. I once posted a german study of very early crohn's disease, where the first signs of crohn's disease where small inflamed lympoid follicles.
These M cells are the entry point of bacteria and dietary antigen, below them you find a dome, a peyer's patch, it's big enough to see with the naked eye. That peyer's patch is full of T cells, B cells and macrophages, it's a dense aggregation of immune cells.
When someone develops inflammation in the small intestine, it is the peyer's patches that initiate that response, it is a response to antigen crossing the epithelial barrier through M cells.
Thank you so much! I have a follow up - I remember you mentioned that an early onset Crohn's case is odd to you. This mom's son is 6, would he have enough time to develop enough peyer's patches? What about M cells? Do they come on scene later during adulthood as well?
kiny
Well-known member
- Joined
- Apr 28, 2011
- Messages
- 3,472
Peyer's patches are exclusive to the ileum and very distal jejenum.
Lymphoid follicles are found in both the small and large intestine.
Both of these are covered with M cells.
Peyer's patches are present in small numbers at birth, but their numbers increase exponentially during puberty, which is the age most people develop crohn's disese.
Lymphoid follicles are not present at birth, but develop after birth in time, due to stimulation of antigen.
Why I find it somewhat odd that children at young age develop crohn's disease, is the simple lack of peyer's patches and lymphoid follicles.
Lymphoid follicles are found in both the small and large intestine.
Both of these are covered with M cells.
Peyer's patches are present in small numbers at birth, but their numbers increase exponentially during puberty, which is the age most people develop crohn's disese.
Lymphoid follicles are not present at birth, but develop after birth in time, due to stimulation of antigen.
Why I find it somewhat odd that children at young age develop crohn's disease, is the simple lack of peyer's patches and lymphoid follicles.
Last edited:
kiny
Well-known member
- Joined
- Apr 28, 2011
- Messages
- 3,472
Right. Which is why the autoimmune theory made so little sense to anyone who has studied infections. Crohn's disease developes where the bacteria are and where bacteria can enter tissue.
The epithelial barrier is a literal physical barrier covered by the mucosa. It is the first line of defense against bacterial invasion. How bacteria like Salmonella and E Coli actually gain entry in tissue is because they exploit these M cells. When these M cells take up this antigen, it crosses into tissue. The immune system sounds the alarm because they found an intruder, it starts recruiting mass numbers of dendritic cells that were sleeping deeper below the surface in peyer's patches. You get antigen presentation, and activation of the adaptive immune system and a full blown immune reaction.
The epithelial barrier is a literal physical barrier covered by the mucosa. It is the first line of defense against bacterial invasion. How bacteria like Salmonella and E Coli actually gain entry in tissue is because they exploit these M cells. When these M cells take up this antigen, it crosses into tissue. The immune system sounds the alarm because they found an intruder, it starts recruiting mass numbers of dendritic cells that were sleeping deeper below the surface in peyer's patches. You get antigen presentation, and activation of the adaptive immune system and a full blown immune reaction.
kiny
Well-known member
- Joined
- Apr 28, 2011
- Messages
- 3,472
The mucosal immune system is acutely aware of what is a pathogen, and what is not. It is never going to launch an immune reaction seen in crohn's disease against commensals in the lumen. This idea that the mucosal immune system one day decided to launch a reaction against the microbiome is baloney. If that was the case you would have inflammation all over the intestine. Instead, crohn's disease is patchy and transmural, it involves pathogens (or pathobionts if you wish) that gained entry to tissue. Crohn's disease is deep tissue inflammation involving bacterial antigen that crossed the epithelial barrier.
It takes many tries but I think I am understanding this better now. I can see why you advocate for EEN because it makes sense by theory and there is also proven efficacy which confirms the theory.
Regarding the autoimmune theory... I think the belief is that people's immune genes in suspect are altered or mutated so with or without the bacterial trigger, the system can't seem to stop fighting at the appropriate time and there are many proposed reasons why the immune system would behave uncontrollably (hygiene theory comes to mind). Or it's a combo situation but the immune system's wacky involvement seems to be in every proposed equation though.
Regarding the autoimmune theory... I think the belief is that people's immune genes in suspect are altered or mutated so with or without the bacterial trigger, the system can't seem to stop fighting at the appropriate time and there are many proposed reasons why the immune system would behave uncontrollably (hygiene theory comes to mind). Or it's a combo situation but the immune system's wacky involvement seems to be in every proposed equation though.
kiny
Well-known member
- Joined
- Apr 28, 2011
- Messages
- 3,472
The adaptive immune response we see in crohn's disease is largely what you would expect to happen during a chronic infection. The NOD2 and ATG16L1 mutation a significant number of people in crohn's disease carry in the Western world signal a delayed initial immune response and autophagy. They're innate immunodefficiencies, but the adaptive response in crohn's disease is appropriate. The immune reaction resolves just fine in people in remission, there's no self-antigen or abnormal immune response in crohn's disease that prolongs inflammation beyond what is expected.
Dr. Hirten said that the trial at Mt. Sinai is doing well and still recruiting. He is hoping to have test results next year. This is all the update I can get.
Here is the trial info: https://clinicaltrials.gov/ct2/show/NCT03808103
Here is the trial info: https://clinicaltrials.gov/ct2/show/NCT03808103
I was actually going to be in that trial, but I am in DC and couldn't make all the required trips to NY.
That would have been very cool if you participated. How are you doing otherwise?
kiny
Well-known member
- Joined
- Apr 28, 2011
- Messages
- 3,472
There will need to be more target-specific treatments for pathogenic E coli, not just because of crohn's disease or SIBO...but also because of urinary tract infections where E Coli can be very antibiotic-resistant.
Antibiotic resistant E Coli is a worldwide problem that needs a solution. And there is an umbrella of diseases that could benefit from new treatments.
Antibiotic resistant E Coli is a worldwide problem that needs a solution. And there is an umbrella of diseases that could benefit from new treatments.
kiny
Well-known member
- Joined
- Apr 28, 2011
- Messages
- 3,472
The biggest clients of companies designing phages aren't even medical atm, they're food and packaging companies. Food companies increasingly use phages to counter foodborne infections.
We are "lucky" that the bacteria found in crohn's disease patients, like pathogenic E Coli, Klebsiella, Listeria...are also a burden in other diseases, and in the food industry. Because it spurs development due to a high potential offset market.
I always said that if we can pinpoint these bacteria, it will be common pathogenic bacteria. It's not going to be some exotic anomaly. Due to the prevalence of crohn's disease, it has to be a bacteria or fungi that is wildly present in the environment. They might be more virulent in crohn's disease, but crohn's disease patients will benefit from the fact they're overlapping strains. And a common pathogenic bacteria will be a problem or nuisance in other industries and diseases too, so there's a big chance that we benefit from this as patients.
We also benefit as patients due to the increasing worldwide prevalence of crohn's disease. It is now a common disease, even in Asia. And while I don't wish this disease on anyone, rare diseases rarely get the funding needed to lead to a cure.
We are "lucky" that the bacteria found in crohn's disease patients, like pathogenic E Coli, Klebsiella, Listeria...are also a burden in other diseases, and in the food industry. Because it spurs development due to a high potential offset market.
I always said that if we can pinpoint these bacteria, it will be common pathogenic bacteria. It's not going to be some exotic anomaly. Due to the prevalence of crohn's disease, it has to be a bacteria or fungi that is wildly present in the environment. They might be more virulent in crohn's disease, but crohn's disease patients will benefit from the fact they're overlapping strains. And a common pathogenic bacteria will be a problem or nuisance in other industries and diseases too, so there's a big chance that we benefit from this as patients.
We also benefit as patients due to the increasing worldwide prevalence of crohn's disease. It is now a common disease, even in Asia. And while I don't wish this disease on anyone, rare diseases rarely get the funding needed to lead to a cure.
Last edited:
kiny
Well-known member
- Joined
- Apr 28, 2011
- Messages
- 3,472
No, there's many reasons why someone might be constipated or have diarrhea.
Yes these bacteria ferment dietary fibers and might contribute to someone being constipated or have diarrhea, but it is a way too complex to draw anything useful from it. Digestion involves pancreas, enzymes, bioavailability of the stuff you eat, etc. The chain of events that take place is so complex.
If someone goes on vacation, has acute gastroenteritis, diarrhea, and you find contaminated food...you can then say the diarrhea was caused by a foodborne infeciton. But you can't do that for crohn's disease, you would have to detect these bacteria in stool or through a biopsy.
Yes these bacteria ferment dietary fibers and might contribute to someone being constipated or have diarrhea, but it is a way too complex to draw anything useful from it. Digestion involves pancreas, enzymes, bioavailability of the stuff you eat, etc. The chain of events that take place is so complex.
If someone goes on vacation, has acute gastroenteritis, diarrhea, and you find contaminated food...you can then say the diarrhea was caused by a foodborne infeciton. But you can't do that for crohn's disease, you would have to detect these bacteria in stool or through a biopsy.
kiny
Well-known member
- Joined
- Apr 28, 2011
- Messages
- 3,472
If you decide to add a bit of fiber to a diet to relieve constipation, crohn's disease patients need to be careful of which fibers they consume. Many bacteria in the intestine use enzymes to break down starch as their fuel, Klebsiella especially. Klebsiella populations bloom on high starch diets.
What bacteria can't easily ferment are structural fibers that lack the energy they seek, like cellulose. Consuming a bit of cellulose to bulk stool is a low risk solution to relieve constipation.
What bacteria can't easily ferment are structural fibers that lack the energy they seek, like cellulose. Consuming a bit of cellulose to bulk stool is a low risk solution to relieve constipation.
Evidence for a Causal Role for Escherichia coli Strains Identified as Adherent-Invasive (AIEC) in Intestinal Inflammation
ABSTRACT
Enrichment of adherent-invasive Escherichia coli (AIEC) has been consistently detected in subsets of inflammatory bowel disease (IBD) patients. Although some AIEC strains cause colitis in animal models, these studies did not systematically compare AIEC with non-AIEC strains, and causal links between AIEC and disease are still disputed. Specifically, it remains unclear whether AIEC shows enhanced pathogenicity compared to that of commensal E. coli found in the same ecological microhabitat and if the in vitro phenotypes used to classify strains as AIEC are pathologically relevant. Here, we utilized in vitro phenotyping and a murine model of intestinal inflammation to systematically compare strains identified as AIEC with those identified as non-AIEC and relate AIEC phenotypes to pathogenicity. Strains identified as AIEC caused, on average, more severe intestinal inflammation. Intracellular survival/replication phenotypes routinely used to classify AIEC positively correlated with disease, while adherence to epithelial cells and tumor necrosis factor alpha production by macrophages did not. This knowledge was then applied to design and test a strategy to prevent inflammation by selecting E. coli strains that adhered to epithelial cells but poorly survived/replicated intracellularly. Two E. coli strains that ameliorated AIEC-mediated disease were subsequently identified. In summary, our results show a relationship between intracellular survival/replication in E. coli and pathology in murine colitis, suggesting that strains possessing these phenotypes might not only become enriched in human IBD but also contribute to disease. We provide new evidence that specific AIEC phenotypes are pathologically relevant and proof of principle that such mechanistic information can be therapeutically exploited to alleviate intestinal inflammation
https://journals.asm.org/doi/pdf/10.1128/msphere.00478-22
ABSTRACT
Enrichment of adherent-invasive Escherichia coli (AIEC) has been consistently detected in subsets of inflammatory bowel disease (IBD) patients. Although some AIEC strains cause colitis in animal models, these studies did not systematically compare AIEC with non-AIEC strains, and causal links between AIEC and disease are still disputed. Specifically, it remains unclear whether AIEC shows enhanced pathogenicity compared to that of commensal E. coli found in the same ecological microhabitat and if the in vitro phenotypes used to classify strains as AIEC are pathologically relevant. Here, we utilized in vitro phenotyping and a murine model of intestinal inflammation to systematically compare strains identified as AIEC with those identified as non-AIEC and relate AIEC phenotypes to pathogenicity. Strains identified as AIEC caused, on average, more severe intestinal inflammation. Intracellular survival/replication phenotypes routinely used to classify AIEC positively correlated with disease, while adherence to epithelial cells and tumor necrosis factor alpha production by macrophages did not. This knowledge was then applied to design and test a strategy to prevent inflammation by selecting E. coli strains that adhered to epithelial cells but poorly survived/replicated intracellularly. Two E. coli strains that ameliorated AIEC-mediated disease were subsequently identified. In summary, our results show a relationship between intracellular survival/replication in E. coli and pathology in murine colitis, suggesting that strains possessing these phenotypes might not only become enriched in human IBD but also contribute to disease. We provide new evidence that specific AIEC phenotypes are pathologically relevant and proof of principle that such mechanistic information can be therapeutically exploited to alleviate intestinal inflammation
https://journals.asm.org/doi/pdf/10.1128/msphere.00478-22
'Role of adherent and invasive Escherichia coli in Crohn’s disease: lessons from the postoperative recurrence model'
Abstract
Objective We used the postoperative recurrence model to better understand the role of adherent and invasive Escherichia coli (AIEC) bacteria in Crohn’s disease (CD), taking advantage of a well-characterised postoperative cohort.
Results AIEC prevalence was twofold higher within the neoterminal ileum at M6 (30.3%) than within the surgical specimen (14.9%) (p<0.001). AIEC within the neoterminal ileum at M6 was associated with higher rate of early ileal lesions (i1) (41.6% vs 17.1%; aRR 3.49 (95% CI 1.01 to 12.04), p=0.048) or ileal lesions (i2b+i3) (38.2% vs 17.1%; aRR 3.45 (95% CI 1.06 to 11.30), p=0.040) compared with no lesion (i0). AIEC within the surgical specimen was predictive of higher risk of i2b-endoscopic postoperative recurrence (POR) (aOR 2.54 (95% CI 1.01 to 6.44), p=0.049) and severe endoscopic POR (aOR 3.36 (95% CI 1.25 to 9.06), p=0.017). While only 5.0% (6/119) of the patients were AIEC-positive at both M0 and M6, 43.7% (52/119), patients with history of positive test for AIEC (M0 or M6) had higher risk of ileal endoscopic POR (aOR 2.32 (95% CI 1.01 to 5.39), p=0.048)), i2b-endoscopic postoperative recurrence (aOR 2.41 (95% CI 1.01 to 5.74); p=0.048) and severe endoscopic postoperative (aOR=3.84 (95% CI 1.32 to 11.18), p=0.013). AIEC colonisation was associated with a specific microbiota signature including increased abundance of Ruminococcus gnavus.
https://gut.bmj.com/content/72/1/39.abstract
Abstract
Objective We used the postoperative recurrence model to better understand the role of adherent and invasive Escherichia coli (AIEC) bacteria in Crohn’s disease (CD), taking advantage of a well-characterised postoperative cohort.
Results AIEC prevalence was twofold higher within the neoterminal ileum at M6 (30.3%) than within the surgical specimen (14.9%) (p<0.001). AIEC within the neoterminal ileum at M6 was associated with higher rate of early ileal lesions (i1) (41.6% vs 17.1%; aRR 3.49 (95% CI 1.01 to 12.04), p=0.048) or ileal lesions (i2b+i3) (38.2% vs 17.1%; aRR 3.45 (95% CI 1.06 to 11.30), p=0.040) compared with no lesion (i0). AIEC within the surgical specimen was predictive of higher risk of i2b-endoscopic postoperative recurrence (POR) (aOR 2.54 (95% CI 1.01 to 6.44), p=0.049) and severe endoscopic POR (aOR 3.36 (95% CI 1.25 to 9.06), p=0.017). While only 5.0% (6/119) of the patients were AIEC-positive at both M0 and M6, 43.7% (52/119), patients with history of positive test for AIEC (M0 or M6) had higher risk of ileal endoscopic POR (aOR 2.32 (95% CI 1.01 to 5.39), p=0.048)), i2b-endoscopic postoperative recurrence (aOR 2.41 (95% CI 1.01 to 5.74); p=0.048) and severe endoscopic postoperative (aOR=3.84 (95% CI 1.32 to 11.18), p=0.013). AIEC colonisation was associated with a specific microbiota signature including increased abundance of Ruminococcus gnavus.
https://gut.bmj.com/content/72/1/39.abstract
kiny
Well-known member
- Joined
- Apr 28, 2011
- Messages
- 3,472
Very good thanks.
Very early signs of crohn's disease are these inflamed ileal lymphoid follicles that then become bigger ulcers in patients with uncontrolled inflammation and you see aggregates of immune cells forming granuloma. These are very similar to early signs of intestinal TB. Clearly a type of pathogen is involved that has entered tissue.
Once the epithelial barrier is compromised, of course lumen content and the fecal stream just exhaexacerbates the inflammation, but the trigger of early onset inflammation is a reaction to a particular pathogen, I don't think it's a dietary particle.
And this pathogen becomes part of the fecal stream high in bacterial antigen. So when you challenge previously unaffected tissue with a fecal stream, you get inflammation a few days later. EN and PN mitigates this, it mitigates the fecal stream and mitigates the amount of lumen content that can enter tissue. That's what EN was designed to do, reduce the fecal stream for astronauts by increasing absorption, but it also reduces the amount of antigen interacting with the epithelial barrier.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3396064/pdf/ijcep0005-0411.pdf
Very early signs of crohn's disease are these inflamed ileal lymphoid follicles that then become bigger ulcers in patients with uncontrolled inflammation and you see aggregates of immune cells forming granuloma. These are very similar to early signs of intestinal TB. Clearly a type of pathogen is involved that has entered tissue.
Once the epithelial barrier is compromised, of course lumen content and the fecal stream just exhaexacerbates the inflammation, but the trigger of early onset inflammation is a reaction to a particular pathogen, I don't think it's a dietary particle.
And this pathogen becomes part of the fecal stream high in bacterial antigen. So when you challenge previously unaffected tissue with a fecal stream, you get inflammation a few days later. EN and PN mitigates this, it mitigates the fecal stream and mitigates the amount of lumen content that can enter tissue. That's what EN was designed to do, reduce the fecal stream for astronauts by increasing absorption, but it also reduces the amount of antigen interacting with the epithelial barrier.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3396064/pdf/ijcep0005-0411.pdf
Last edited:
kiny
Well-known member
- Joined
- Apr 28, 2011
- Messages
- 3,472
When unaffected tissue comes into contact with the fecal stream, it takes a few days before you can see it in inflammatory markers. So these AIEC or other antigen breach the intestinal wall, they cross M cells in the ileum. A delayed innate immune response happens in CD patients, a delayed neutrophil response and a compromised macrophage response. Dendritic cells activate T cells, 2 to 3 days later you will see a massive T lymphocyte response to try to kill intracellular bacteria like AIEC. But by then, luminal content will have entered tissue, and you get this huge immune response that takes a long time to resolve, resolution of inflammation is sped up by limiting luminal antigen with EN, specifically designed to limit intestinal content. These AIEC bacteria are not fully killed, but remain dorment and the disease isn't cured like it is for many gastroenteritis infections. The only resolution would be targeting AIEC.
Last edited:
kiny
Well-known member
- Joined
- Apr 28, 2011
- Messages
- 3,472
Why the ileum becomes an easy question to answer if AIEC are directly involved in initiation of the inflammatory cascade.
The strategy of AIEC is similar to its close relatives Salmonellae and Shigellae. They all invade ileal M cells. This is all not new stuff, we have known pathogenic E Coli was capable of invading M cells and sticking to and breaking down the epithelial barrier for decades. I always thought crohn's would be explained by some well known pathogen due to the sheer prevalence of the disease. The initial symptoms crohn's disease patients have are not that different from bacterial gastroenteritis like a foodborne salmonella infection.
The strategy of AIEC is similar to its close relatives Salmonellae and Shigellae. They all invade ileal M cells. This is all not new stuff, we have known pathogenic E Coli was capable of invading M cells and sticking to and breaking down the epithelial barrier for decades. I always thought crohn's would be explained by some well known pathogen due to the sheer prevalence of the disease. The initial symptoms crohn's disease patients have are not that different from bacterial gastroenteritis like a foodborne salmonella infection.
kiny
Well-known member
- Joined
- Apr 28, 2011
- Messages
- 3,472
Not sure. In UC the colonic inflammation possibly involves autoreactive cells and loss of tolerance, people with UC have inflammation all over the intestine. It's possible UC has nothing to do with pathogens.
This is not the case for crohn's disease involving the colon, there's patchy and deep transmural inflammation and there's granuloma, which indicates bacteria have entered tissue. I don't understand the colon nearly as well as the small intestine, there's always a possibility that they have a common explanation, but because the colon lacks peyer's patches, it's hard to compare them.
This is not the case for crohn's disease involving the colon, there's patchy and deep transmural inflammation and there's granuloma, which indicates bacteria have entered tissue. I don't understand the colon nearly as well as the small intestine, there's always a possibility that they have a common explanation, but because the colon lacks peyer's patches, it's hard to compare them.
kiny
Well-known member
- Joined
- Apr 28, 2011
- Messages
- 3,472
G are the goblet cells secreting mucus.
P are the paneth cells that secrete antimicrobioals, our own antibiotics factory if you wish.
TLRs are toll like receptors that recognize pathogens, you can see them displayed in the epithelium and on the macrophage in the lamina propria. They're actually very specifically placed, even their distance to lumen content is important. Because they need to both help recognize pathogens but also be tolerant towards non-antigen.
M are the M cells that cover the peyer's patch.
You can see the peyer's patch below the epithelium. They're ileal specific, very well structured and highly organised. They get antigen from the M cells that cover them. They're full of B lymphocytes, a bit less T lymphocyes and lots of dendritic cells that can do antigen presentation. They're shown as this disconnected ball, but in reality they are highly connected, it's lymphatic tissue, lymphocytes have an express highway from the blood to the peyer's patches.
You can also see all these cytokines being secreted everywhere, the stuff starting with IL are the interleukins, then you have TNF, and transforming growth factor-b. They're tiny proteins, they're signaling to other immune cells, inducing fevers, they can be pro or anti-inflammatory, they're the orchestrators of the immune system.
P are the paneth cells that secrete antimicrobioals, our own antibiotics factory if you wish.
TLRs are toll like receptors that recognize pathogens, you can see them displayed in the epithelium and on the macrophage in the lamina propria. They're actually very specifically placed, even their distance to lumen content is important. Because they need to both help recognize pathogens but also be tolerant towards non-antigen.
M are the M cells that cover the peyer's patch.
You can see the peyer's patch below the epithelium. They're ileal specific, very well structured and highly organised. They get antigen from the M cells that cover them. They're full of B lymphocytes, a bit less T lymphocyes and lots of dendritic cells that can do antigen presentation. They're shown as this disconnected ball, but in reality they are highly connected, it's lymphatic tissue, lymphocytes have an express highway from the blood to the peyer's patches.
You can also see all these cytokines being secreted everywhere, the stuff starting with IL are the interleukins, then you have TNF, and transforming growth factor-b. They're tiny proteins, they're signaling to other immune cells, inducing fevers, they can be pro or anti-inflammatory, they're the orchestrators of the immune system.
and that is most of the time. :/
kiny
Well-known member
- Joined
- Apr 28, 2011
- Messages
- 3,472
It is incredibly organised, the intestine is full of immune cells. There are more lymphocytes in the intestine than anywhere else in the body. The epithelial is full of CD8 T cells and the lamina propria below it is full of CD8, CD4, macrophages, dendritic cells. The immune cells that don't generally stick around are neutrophils, unless there is some sort or infection of inflammation, then thousands of neutrophils will migrate to intestinal tissue. And then to know that the small intestine is the organ with the fastest cell turnover, that has to regenerate the fastest of any organ. It is quite crazy.
- Joined
- Nov 24, 2017
- Messages
- 419
One thing about Crohn's that I think is pretty clear but not well understood is the idea of downstream effects. I'm pretty sure that somehow areas of inflammation in the small intestine often cause inflammation in the large intestine, because one thing that's been observed is that small intestinal resection can result in healing of ulcers in the large intestine. I don't know if this is due to pathogens being pushed downstream or what.
Only if we had another kiny who understands the colon, then this forum would be complete.
Crohn’s disease-associated AIEC inhibiting intestinal epithelial cell-derived exosomal let-7b expression regulates macrophage polarization to exacerbate intestinal fibrosis
https://www.tandfonline.com/doi/full/10.1080/19490976.2023.2193115#.ZB7p2qN3shE.twitter
https://www.tandfonline.com/doi/full/10.1080/19490976.2023.2193115#.ZB7p2qN3shE.twitter
Similar threads
