Peyer's patch | |
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Details | |
System | Lymphatic system |
Identifiers | |
Latin | noduli lymphoidei aggregati |
MeSH | D010581 |
TA98 | A05.6.01.014 A05.7.02.009 |
TA2 | 2960, 2978 |
TH | H3.04.03.0.00020 |
FMA | 15054 |
Anatomical terminology |
Peyer's patches (or aggregated lymphoid nodules) are organized lymphoid follicles, named after the 17th-century Swiss anatomist Johann Conrad Peyer. [1] They are an important part of gut associated lymphoid tissue usually found in humans in the lowest portion of the small intestine, mainly in the distal jejunum and the ileum, but also could be detected in the duodenum. [2]
Peyer's patches had been observed and described by several anatomists during the 17th century, [3] but in 1677 Swiss anatomist Johann Conrad Peyer (1653–1712) described the patches so clearly that they were eventually named after him. [1] [4] However, Peyer regarded them as glands which discharged, into the small intestine, some substance which facilitated digestion. It was not until 1850 that the Swiss physician Rudolph Oskar Ziegler (1828–1881) suggested, after careful microscopic examination, that Peyer's patches were actually lymph glands. [5]
Peyer's patches are observable as elongated thickenings of the intestinal mucosa measuring a few centimeters in length. About 100 are found in humans. Microscopically, Peyer's patches appear as oval or round lymphoid follicles (similar to lymph nodes) located in the mucosa layer of the ileum and extend into the submucosa layer. The number of Peyer's patches peaks at age 15–25 and then declines during adulthood. [2] In the distal ileum, they are numerous and they form a lymphoid ring. At least 46% of Peyer's patches are concentrated in the distal 25 cm of ileum in humans. It is important to note that there are large variations in size, shape, and distribution of Peyer's patches from one individual to another one. [6] In adults, B lymphocytes are seen to dominate the follicles' germinal centers. T lymphocytes are found in the zones between follicles. Among the mononuclear cells, CD4+/CD25+ (10%) cells and CD8+/CD25+ (5%) cells are more abundant in Peyer's patches than in the peripheral blood. [7]
Peyer's patches are characterized by the follicle-associated epithelium (FAE), which covers all lymphoid follicles. [8] FAE differs from typical small intestinal villus epithelium: it has fewer goblet cells [9] therefore mucus layer is thinner, [10] and it is also characterized by the presence of specialized M cells or microfold cells, which provide uptake and transport of antigens from lumen. [8] Moreover, basal lamina of follicle-associated epithelium is more porous compared to intestinal villus. [11] Finally, follicle-associated epithelium is less permeable for ions and macromolecules, basically due to higher expression of tight junction proteins. [12]
Because the lumen of the gastrointestinal tract is exposed to the external environment, much of it is populated with potentially pathogenic microorganisms. Peyer's patches thus establish their importance in the immune surveillance of the intestinal lumen and in facilitating production of the immune response within the mucosa.
Pathogenic microorganisms and other antigens entering the intestinal tract encounter macrophages, dendritic cells, B-lymphocytes, and T-lymphocytes found in Peyer's patches and other sites of gut-associated lymphoid tissue (GALT). Peyer's patches thus act for the gastrointestinal system much as the tonsils act for the respiratory system, trapping foreign particles, surveilling them, and destroying them. Peyer's patches have adaptive immune capabilities through inducing selective apoptosis of B cells due CD122-targeted interleukin-2 (IL-2) signaling. Additionally, the B cell population can be restored. [13]
Peyer's patches are covered by a special follicle-associated epithelium that contains specialized cells called microfold cells (M cells) which sample antigen directly from the lumen and deliver it to antigen-presenting cells (located in a unique pocket-like structure on their basolateral side). Dendritic cells and macrophages can also directly sample the lumen by extending dendrites through transcellular M cell-specific pores. [14] [15] At the same time the paracellular pathway of follicle-associated epithelium is closed tightly to prevent penetration of antigens and continuous contact with immune cells. [16] T cells, B-cells and memory cells are stimulated upon encountering antigen in Peyer's patches. These cells then pass to the mesenteric lymph nodes where the immune response is amplified. Activated lymphocytes pass into the blood stream via the thoracic duct and travel to the gut where they carry out their final effector functions. The maturation of B-lymphocytes takes place in the Peyer's patch.
Although important in the immune response, excessive growth of lymphoid tissue in Peyer's patches is pathologic, as hypertrophy of Peyer's patches has been closely associated with idiopathic intussusception.
Having too many or larger than normal Peyer's patches is associated with an increased risk of prion diseases, and intussusception in children. A history of viral illness is a risk factor for enlarged or inflamed Peyer's patches. [17]
Salmonella typhi and poliovirus also target this section of the intestine. [18]
Disturbances in the gut microbiota and immune regulation within Peyer's patches are implicated in the pathogenesis of autoimmune diseases, such as Crohn's disease, where chronic inflammation can arise due to overactive immune responses. [19] As Peyer's patches are packed with immune cells and produce protective proteins such as secretory IgA to maintain gut balance, their dysfunction can trigger inappropriate immune responses, driving the inflammation and tissue damage characteristic of autoimmune diseases. [20]
The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphoid organs, lymphatic tissue and lymph. Lymph is a clear fluid carried by the lymphatic vessels back to the heart for re-circulation. The Latin word for lymph, lympha, refers to the deity of fresh water, "Lympha".
A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that include B and T cells. Lymph nodes are important for the proper functioning of the immune system, acting as filters for foreign particles including cancer cells, but have no detoxification function.
The ileum is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine may be used instead of ileum. Its main function is to absorb vitamin B12, bile salts, and whatever products of digestion that were not absorbed by the jejunum.
The jejunum is the second part of the small intestine in humans and most higher vertebrates, including mammals, reptiles, and birds. Its lining is specialized for the absorption by enterocytes of small nutrient molecules which have been previously digested by enzymes in the duodenum.
The small intestine or small bowel is an organ in the gastrointestinal tract where most of the absorption of nutrients from food takes place. It lies between the stomach and large intestine, and receives bile and pancreatic juice through the pancreatic duct to aid in digestion. The small intestine is about 5.5 metres long and folds many times to fit in the abdomen. Although it is longer than the large intestine, it is called the small intestine because it is narrower in diameter.
Paratuberculosis is a contagious, chronic and sometimes fatal infection that primarily affects the small intestine of ruminants. It is caused by the bacterium Mycobacterium avium subspecies paratuberculosis. Infections normally affect ruminants, but have also been seen in a variety of nonruminant species, including rabbits, foxes, and birds. Horses, dogs, and nonhuman primates have been infected experimentally. Paratuberculosis is found worldwide, with some states in Australia being the only areas proven to be free of the disease. At least in Canada, the signs of BJD usually start when cattle are four to seven years of age, and then usually only are diagnosed in one animal at a time. Cattle "with signs of Johne’s disease shed billions of bacteria through their manure and serve as a major source of infection for future calves."
Gut-associated lymphoid tissue (GALT) is a component of the mucosa-associated lymphoid tissue (MALT) which works in the immune system to protect the body from invasion in the gut.
The mucosa-associated lymphoid tissue (MALT), also called mucosa-associated lymphatic tissue, is a diffuse system of small concentrations of lymphoid tissue found in various submucosal membrane sites of the body, such as the gastrointestinal tract, nasopharynx, thyroid, breast, lung, salivary glands, eye, and skin. MALT is populated by lymphocytes such as T cells and B cells, as well as plasma cells, dendritic cells and macrophages, each of which is well situated to encounter antigens passing through the mucosal epithelium. In the case of intestinal MALT, M cells are also present, which sample antigen from the lumen and deliver it to the lymphoid tissue. MALT constitute about 50% of the lymphoid tissue in human body. Immune responses that occur at mucous membranes are studied by mucosal immunology.
Immune tolerance, also known as immunological tolerance or immunotolerance, refers to the immune system's state of unresponsiveness to substances or tissues that would otherwise trigger an immune response. It arises from prior exposure to a specific antigen and contrasts the immune system's conventional role in eliminating foreign antigens. Depending on the site of induction, tolerance is categorized as either central tolerance, occurring in the thymus and bone marrow, or peripheral tolerance, taking place in other tissues and lymph nodes. Although the mechanisms establishing central and peripheral tolerance differ, their outcomes are analogous, ensuring immune system modulation.
Microfold cells are found in the gut-associated lymphoid tissue (GALT) of the Peyer's patches in the small intestine, and in the mucosa-associated lymphoid tissue (MALT) of other parts of the gastrointestinal tract. These cells are known to initiate mucosal immunity responses on the apical membrane of the M cells and allow for transport of microbes and particles across the epithelial cell layer from the gut lumen to the lamina propria where interactions with immune cells can take place.
High endothelial venules (HEV) are specialized post-capillary venules characterized by plump endothelial cells as opposed to the usual flatter endothelial cells found in regular venules. HEVs enable lymphocytes circulating in the blood to directly enter a lymph node.
Lymphocyte homing receptors are cell adhesion molecules expressed on lymphocyte cell membranes that recognize addressins on target tissues. Lymphocyte homing refers to adhesion of the circulating lymphocytes in blood to specialized endothelial cells within lymphoid organs. These diverse tissue-specific adhesion molecules on lymphocytes and on endothelial cells contribute to the development of specialized immune responses.
Lymphotoxin-alpha (LT-α) formerly known as tumor necrosis factor-beta (TNF-β) is a protein that in humans is encoded by the LTA gene. Belonging to the hematopoietic cell line, LT-α exhibits anti-proliferative activity and causes the cellular destruction of tumor cell lines. As a cytotoxic protein, LT-α performs a variety of important roles in immune regulation depending on the form that it is secreted as. Unlike other members of the TNF superfamily, LT-α is only found as a soluble homotrimer, when found at the cell surface it is found only as a heterotrimer with LTβ.
The intestinal epithelium is the single cell layer that forms the luminal surface (lining) of both the small and large intestine (colon) of the gastrointestinal tract. Composed of simple columnar epithelium its main functions are absorption, and secretion. Useful substances are absorbed into the body, and the entry of harmful substances is restricted. Secretions include mucins, and peptides.
Mucosal immunology is the study of immune system responses that occur at mucosal membranes of the intestines, the urogenital tract, and the respiratory system. The mucous membranes are in constant contact with microorganisms, food, and inhaled antigens. In healthy states, the mucosal immune system protects the organism against infectious pathogens and maintains a tolerance towards non-harmful commensal microbes and benign environmental substances. Disruption of this balance between tolerance and deprivation of pathogens can lead to pathological conditions such as food allergies, irritable bowel syndrome, susceptibility to infections, and more.
The gastrointestinal wall of the gastrointestinal tract is made up of four layers of specialised tissue. From the inner cavity of the gut outwards, these are the mucosa, the submucosa, the muscular layer and the serosa or adventitia.
Gut-specific homing is the mechanism by which activated T cells and antibody-secreting cells (ASCs) are targeted to both inflamed and non-inflamed regions of the gut in order to provide an effective immune response. This process relies on the key interaction between the integrin α4β7 and the addressin MadCAM-1 on the surfaces of the appropriate cells. Additionally, this interaction is strengthened by the presence of CCR9, a chemokine receptor, which interacts with TECK. Vitamin A-derived retinoic acid regulates the expression of these cell surface proteins.
The intestinal mucosal barrier, also referred to as intestinal barrier, refers to the property of the intestinal mucosa that ensures adequate containment of undesirable luminal contents within the intestine while preserving the ability to absorb nutrients. The separation it provides between the body and the gut prevents the uncontrolled translocation of luminal contents into the body proper. Its role in protecting the mucosal tissues and circulatory system from exposure to pro-inflammatory molecules, such as microorganisms, toxins, and antigens is vital for the maintenance of health and well-being. Intestinal mucosal barrier dysfunction has been implicated in numerous health conditions such as: food allergies, microbial infections, irritable bowel syndrome, inflammatory bowel disease, celiac disease, metabolic syndrome, non-alcoholic fatty liver disease, diabetes, and septic shock.
Nasal- or nasopharynx- associated lymphoid tissue (NALT) represents immune system of nasal mucosa and is a part of mucosa-associated lymphoid tissue (MALT) in mammals. It protects body from airborne viruses and other infectious agents. In humans, NALT is considered analogous to Waldeyer's ring.
Bronchus-associated lymphoid tissue (BALT) is a tertiary lymphoid structure. It is a part of mucosa-associated lymphoid tissue (MALT), and it consists of lymphoid follicles in the lungs and bronchus. BALT is an effective priming site of the mucosal and systemic immune responses.
Unlike S hadar peritonitis, S typhi peritonitis is due to perforation of Peyer's patches.