Peyer’s patches are small, organized clusters of lymphoid tissue found in the mucosa and submucosa of the small intestine, primarily in the ileum.[4] They are part of the gut-associated lymphoid tissue (GALT) and play a crucial role in the immune system by monitoring intestinal bacteria and generating immune responses against potential pathogens. Peyer’s patches are covered by specialized epithelial cells, including microfold cells (M cells), which facilitate the sampling of antigens from the intestinal lumen and initiate immune reactions. These patches act as sites where immune cells, such as B and T lymphocytes, are activated and contribute to the body’s defense against ingested pathogens.[6]
Structure
Peyer’s patches are highly organized lymphoid tissues with distinct architectural features that facilitate their role in immune surveillance and response. Their structure includes multiple layers and specialized cell types.
Dome Region
- Located at the surface of Peyer’s patches, just beneath the intestinal epithelium.
- Contains microfold cells (M cells), which transport antigens from the intestinal lumen to underlying immune cells.
- Rich in dendritic cells, macrophages, and other antigen-presenting cells (APCs) that initiate immune responses.
Germinal Centers
- Found within the Peyer’s patches, germinal centers are areas where B lymphocytes proliferate, differentiate, and undergo somatic hypermutation to produce high-affinity antibodies.
- Surrounded by T lymphocytes and follicular dendritic cells, which help regulate the immune response.[1]
Follicle-Associated Epithelium (FAE)
- The epithelium covering Peyer’s patches is thinner and specialized, facilitating the uptake of antigens.
- Contains fewer goblet cells and more M cells compared to regular intestinal epithelium.
Subepithelial Dome (SED)
- Beneath the follicle-associated epithelium, this region contains dendritic cells, T cells, and B cells.
- Acts as a communication hub between the epithelial surface and the lymphoid tissue.
T-Cell Zone
- Located adjacent to the germinal centers, this area is populated by T lymphocytes.
- Facilitates interactions between T cells, dendritic cells, and B cells for initiating adaptive immune responses.
Supporting Stroma
The structure of Peyer’s patches is maintained by a network of reticular fibers and stromal cells that provide mechanical support and promote cell migration.
Location
Peyer’s patches are strategically located in the small intestine, where they monitor the contents of the gastrointestinal (GI) tract for pathogens and antigens. Their distribution and concentration vary depending on the region of the intestine:
Small Intestine
- Ileum: Peyer’s patches are most abundant and prominent in the ileum, the distal part of the small intestine.[8] This region has a high bacterial load, making it a critical site for immune surveillance.
- Jejunum: Fewer and smaller Peyer’s patches are found in the jejunum compared to the ileum.
- Duodenum: Rarely contains Peyer’s patches, as this region is primarily involved in digestion and has a relatively lower bacterial population.
Mucosa and Submucosa
- Peyer’s patches are embedded within the mucosal and submucosal layers of the small intestine.
- They are visible as small, raised oval or round areas on the inner surface of the intestine when viewed macroscopically.
Lymphatic System Connection
Peyer’s patches are connected to the broader lymphatic system via lymphatic vessels, allowing the transport of activated immune cells to other lymphoid tissues for a systemic immune response.
Their strategic placement in the ileum ensures effective sampling of intestinal antigens and microbes, facilitating the body’s defense against pathogens while maintaining tolerance to beneficial gut flora and dietary antigens.
Function
Peyer’s patches are critical components of the immune system within the gastrointestinal (GI) tract. Their functions are focused on immune surveillance, antigen sampling, and initiating immune responses to maintain gut health and protect against pathogens.
Immune Surveillance
- Peyer’s patches monitor the intestinal lumen for antigens, including pathogens, dietary molecules, and components of the gut microbiota.[7]
- Specialized microfold cells (M cells) in the follicle-associated epithelium transport antigens from the lumen to the immune cells within Peyer’s patches.
Activation of Immune Responses
- Once antigens are presented by dendritic cells to T and B lymphocytes within the patches, an adaptive immune response is initiated.
- B lymphocytes: Proliferate and differentiate in the germinal centers of Peyer’s patches, producing antigen-specific antibodies, primarily immunoglobulin A (IgA).
- T lymphocytes: Assist in regulating the immune response and maintaining tolerance to non-harmful antigens, such as commensal bacteria and dietary proteins.
IgA Production
- Peyer’s patches are a major site for the production of secretory IgA (sIgA), an antibody that is transported into the intestinal lumen.
- sIgA binds to pathogens, toxins, and antigens, neutralizing them and preventing their adhesion to the intestinal epithelium.
Gut-Associated Lymphoid Tissue (GALT) Coordination
- Peyer’s patches are integral to the gut-associated lymphoid tissue (GALT), a larger network of immune cells and structures in the GI tract.
- They communicate with mesenteric lymph nodes and other lymphoid tissues to mount localized and systemic immune responses.
Maintenance of Gut Microbiota Balance
- Peyer’s patches help maintain a healthy balance of gut flora by tolerating beneficial bacteria while mounting immune responses against harmful pathogens.
Development of Oral Tolerance
- Peyer’s patches play a role in oral tolerance, preventing inappropriate immune responses to dietary antigens and commensal bacteria.
Peyer’s patches are indispensable for maintaining intestinal and systemic immunity.[5] Their ability to balance immune activation and tolerance ensures gut health and prevents harmful inflammation.
Development and Variability
Peyer’s patches develop during fetal life and undergo changes throughout an individual’s lifespan. Their size, number, and activity vary depending on age, location, and environmental factors.
Development
- Fetal Development:
- Peyer’s patches begin forming during embryogenesis.
- Initial development starts with the aggregation of lymphoid cells in the intestinal wall under the influence of signaling molecules like lymphotoxin and cytokines.
- By the third trimester, Peyer’s patches are structurally mature, containing B and T cell zones.
- Postnatal Development:
- After birth, exposure to intestinal microbes and antigens stimulates the growth and activation of Peyer’s patches.
- This interaction helps shape the gut immune system and establishes tolerance to beneficial bacteria.
Age-Related Changes
- Childhood:
- Peyer’s patches are more numerous and active in children, reflecting their role in developing immune tolerance and protecting against new antigens.
- Their high activity corresponds to the immune system’s need to adapt to a diverse microbial environment.
- Adulthood:
- The number of Peyer’s patches stabilizes, and their activity remains essential for ongoing immune surveillance and response.
- However, they may shrink slightly with age.
- Aging:
- In elderly individuals, Peyer’s patches may become less active, reducing their ability to respond to antigens effectively.
- This decline is associated with immunosenescence, which may contribute to increased susceptibility to infections.
Variability
- Individual Variation:
- The number and size of Peyer’s patches can vary between individuals, influenced by genetic factors and environmental exposure.[3]
- Species Differences:
- Peyer’s patches are present in mammals and have a similar immune role across species, although their distribution and structure may differ.
- Microbial Influence:
- The composition of the gut microbiota can influence the development and activity of Peyer’s patches.
- A diverse microbiota tends to promote more robust immune responses and better maintenance of tolerance.
Clinical Significance
Peyer’s patches play a vital role in gastrointestinal immunity, and their dysfunction or involvement in disease can have significant clinical implications:
- Infections:
- Peyer’s patches are entry points for certain pathogens, such as Salmonella and Yersinia, which exploit M cells to invade the intestinal epithelium.
- Viral infections, like poliovirus, can also target Peyer’s patches for replication and spread.
- Inflammatory Bowel Disease (IBD):
- Dysregulation of Peyer’s patch activity is associated with conditions like Crohn’s disease, where excessive immune activation leads to chronic intestinal inflammation.
- Oral Vaccination:
- Peyer’s patches are key targets for oral vaccines, such as those for cholera and polio, as they are essential for inducing mucosal immunity.
- Immune Tolerance:
- Dysfunction in Peyer’s patches may contribute to food allergies or autoimmune conditions by disrupting the balance of immune tolerance and response.[2]
- Cancer:
- Peyer’s patches can be sites of lymphoma development, such as mucosa-associated lymphoid tissue (MALT) lymphoma, a type of cancer originating in gut-associated lymphoid tissue.
