The Science behind “Cells at Work!!” Episode 2b: “Peyer’s Patch”

In this episode, Neutrophil takes the red blood cells on a tour to the small intestine. On the way to the tea room, Killer T Cell stops and berates Neutrophil for not focusing on his job. Their argument gets cut short; though, by Campylobacter who invades the gut and demands the white blood cells to help him and his friends establish a colony. Intestinal Epithelial Cell, being taken as a hostage, tells Campylobacter about an area in the intestine where it is easy to infiltrate and infect. Campylobacter releases the hostage and goes inside the area, only to be met by M Cell who tells him to enjoy his last meal. Campylobacter suddenly gets surprised by the white blood cells who attack him and his friends, forcing them to flee. Killer T Cell forgives Neutrophil for underestimating him, only to take it back when Neutrophil forgets to serve tea to the red blood cells and rushes out of the room.

In this blog post, I will describe what Campylobacter bacteria are and how they cause gastrointestinal infection. I will then describe what Peyer’s patches are and how they assist in detecting and responding to gastrointestinal infection.

About Campylobacter bacteria

Schematic	Microscopic	Anime

Campylobacter are spirally-shaped rod bacteria with a flagellum that allows them to move around in a spiral fashion. They are microaerophiles, growing optimally at a lower concentration of oxygen (5-10%) than the atmosphere (typically 21%). Campylobacter typically colonise the gastrointestinal tracts of a variety of wild and domesticated animals, particularly farm animals such as chicken, cattle, pigs and sheep; birds such as ducks and seagulls and pets such as cats and dogs. There are 30 species of Campylobacter, most of which are associated with food poisoning episodes called Campylobacteriosis. The two most common Campylobacter bacteria that cause Campylobacteriosis are Campylobacter jejuni and Campylobacter coli.

Humans are typically infected with C. jejuni or C. coli by consuming raw, undercooked or contaminated food and drinks, particularly from chickens (hence the piece of fried chicken containing Campylobacter in the episode). Campylobacter attaches to the gastrointestinal epithelium, allowing them to establish a colony to cause infection. This promotes inflammation in the small intestine (enteritis) and colon (colitis), producing gastrointestinal symptoms such as diarrhoea, abdominal pain, vomiting and bloody stools as well as systemic symptoms such as fever, headache and muscle pain. C. jejuni and C. coli also release a variety of toxins and proteins to mediate infection. The most well-known Campylobacter toxin is cytolethal distending toxin (CDT). This toxin stops the proliferation of epithelial cells in the gastrointestinal tract by preventing cell division from happening. The remaining cells die off, breaking down the epithelial barrier.

Campylobacter bacteria can also spread to other organs via the bloodstream, causing inflammation in other organs such as the linings of the spinal cord and brain (meningitis), pancreas (pancreatitis), the cardiac endocardium (endocarditis) and the kidneys (nephritis). In particular, C. jejuni can produce a post-infection complication called Guillain-Barré Syndrome. This is an autoimmune disease where the immune system attacks its own peripheral nerves, causing progressive paralysis that spreads throughout the body and may lead to death.

The structure of Peyer’s patches

The gastrointestinal tract is a potential route of infection for pathogens that are taken up in contaminated food and drink. The gastrointestinal tract has a range of physical barriers that prevent infection such as commensal bacteria and gastric juices. The gut-associated lymphoid tissues (GALT) is another barrier to infection for gut-associated pathogens. GALT are a network of lymphoid tissues in the gastrointestinal tract consisting of white blood cells such as macrophages, dendritic cells (DCs) and B and T cells. GALT is designed to sample the contents of the gastrointestinal tract and activate an immune response when it detects pathogens. 

The most important GALT structures in the small intestine are the Peyer’s patches, named after the Swiss pathologist Johann Conrad Peyer who first described them in 1677. Peyer’s patches, appearing as small domes on the surface of the small intestine, can be found in areas where villi are scarce. They are designed to sample the gut contents and detect pathogens in specific areas of the small intestine without making the whole gut epithelium susceptible to infection. Peyer’s patches consist of aggregated lymphoid follicles surrounded by the follicle-associated epithelium (FAE). The follicles have germinal centres containing B cells and are surrounded by DCs and T cells.

Schematic	Microscopic	Anime

The FAE has no IgA antibody or mucus, making it easy for pathogens to stick to the FAE. Nevertheless, the FAE does have M (microfold) cells squeezed in between normal epithelial cells (called enterocytes). M cells are designed to transport pathogens and other molecules from the lumen of the small intestine to the Peyer’s patch where it can be sampled by white blood cells. The M cell has a smooth apical (surface) membrane that pathogens can adhere to and a convoluted basal (basement) membrane that forms a pocket where macrophages and DCs can fit. This facilitates the M cell’s role in transporting pathogens from the small intestine to the macrophages and DCs inside the Peyer’s patch. 

How do Peyer’s patches work? 

M cells sample the contents of the gut lumen by phagocytosis or endocytosis. The former process is used to take up pathogens such as Campylobacter that adhere to M cells while the latter process engulfs the gut lumen en masse to collect smaller molecules such as toxins. From there, the pathogen or small molecules are transported through the M cell to the Peyer’s patch, where macrophages and DCs receive the pathogen or small molecules and degrade them. 

The macrophages and DCs then travel into the Peyer’s patch, where the DCs presents the processed antigen to T cells to stimulate their activation and proliferation. In turn, some activated T cells will enter the follicle, where it will activate B cells on the edge of the follicle. Activated B cells will then enter the germinal centres, where it will transform into plasma cells to secrete IgA antibodies to neutralise pathogens in the gut and prevent infection. Other activated T cells will migrate from the Peyer’s patch to the mesenteric lymph nodes behind the small intestine to undergo further activation. Once further activated, they will go back to the small intestine by firstly entering the bloodstream and then returning to the small intestine to assist in immune responses against the pathogen. 

Conclusion

Peyer’s patches are specialised GALT structures in the small intestine that inspect the lumen for pathogens such as Campylobacter and small molecules such as toxins. M cells play an important role in Peyer’s patches as they transport pathogens and small molecules from the small intestine lumen to the white blood cells in the Peyer’s patch. These white blood cells are able to trigger an immune response in the small intestine against the pathogen, not only eliminating the pathogen from the gut but also preventing it from spreading to other parts of the body. This allows the person to recover from food poisoning episodes such as Campylobacteriosis. 

In the next blog post, I will skip ahead to the second part of the next episode to describe in detail what acne is, what causes acne and how it can be treated. See you then!