Mucosa Associated Lymphoid Tissues (MALT)

Mucosa associated lymphoid tissues (MALT) are collections of immune cells that are located in various mucosal surfaces of the body, such as the respiratory, gastrointestinal, and urogenital tracts. MALT is part of the mucosal immune system, which is the largest and most diverse component of the immune system. The mucosal immune system protects the body from pathogens and foreign substances that enter through the mucosal surfaces, which are exposed to the external environment.

MALT consists of different types of lymphoid tissues that have similar functions but differ in their anatomical locations and structures. The main types of MALT are:

• Nasal-associated lymphoid tissue (NALT), which is found in the nasal cavity and the pharynx, especially the tonsils.
• Gut-associated lymphoid tissue (GALT), which is found in the small and large intestines, especially the Peyer`s patches.
• Bronchus-associated lymphoid tissue (BALT), which is found in the lungs and the bronchi.

MALT plays a crucial role in initiating and regulating immune responses to mucosal antigens. MALT can recognize and respond to a wide range of antigens, including bacteria, viruses, fungi, parasites, food antigens, and self-antigens. MALT can also generate immunological memory and tolerance to prevent excessive or harmful immune reactions.

One of the main features of MALT is the production of secretory immunoglobulin A (sIgA), which is the most abundant antibody class in mucosal secretions. sIgA can bind and neutralize pathogens and toxins, prevent their attachment and invasion to mucosal cells, and modulate their interactions with commensal microbiota. sIgA can also regulate inflammation and immune activation in the mucosa.

Another important feature of MALT is the presence of specialized epithelial cells called M cells, which are responsible for transporting antigens from the mucosal lumen to the underlying lymphoid tissue. M cells can sample antigens from various sources, such as microorganisms, food particles, or apoptotic cells. M cells then deliver the antigens to antigen-presenting cells (APCs), such as dendritic cells and macrophages, which process and present them to T cells and B cells. This process triggers adaptive immune responses that are tailored to the specific antigen.

In summary, MALT is a vital part of the mucosal immune system that protects the body from mucosal pathogens and maintains mucosal homeostasis. MALT consists of different types of lymphoid tissues that share common functions but differ in their locations and structures. MALT can recognize and respond to a variety of antigens through sIgA production and antigen sampling by M cells. MALT can also generate immunological memory and tolerance to ensure appropriate and balanced immune responses.

Mucosa-associated lymphoid tissue (MALT) is a type of secondary lymphoid tissue that is found in various mucosal surfaces of the body, such as the respiratory, digestive, and urogenital tracts. MALT consists of discrete aggregates of lymphocytes and antigen-presenting cells (APCs) that are embedded in the mucosal epithelium or the underlying lamina propria. MALT can be divided into two main categories: organized MALT and diffuse MALT.

Organized MALT refers to the well-defined structures that contain lymphoid follicles with germinal centers, where B cells proliferate and differentiate into plasma cells and memory cells. Organized MALT also has interfollicular regions, where T cells and APCs interact, and subepithelial dome regions, where antigens are sampled and presented by specialized epithelial cells called M cells. Organized MALT includes nasal-associated lymphoid tissue (NALT), gut-associated lymphoid tissue (GALT), bronchus-associated lymphoid tissue (BALT), and others.

Diffuse MALT refers to the scattered lymphocytes and APCs that are dispersed throughout the mucosal epithelium and lamina propria. Diffuse MALT does not have distinct follicles or germinal centers, but it plays an important role in providing local immunity and producing secretory IgA antibodies that are transported across the mucosal barrier.

The structure of MALT allows it to perform its functions of sensing, responding, and regulating the immune system in response to various antigens that enter the body through the mucosal surfaces. MALT can initiate both innate and adaptive immune responses, as well as maintain immune tolerance to commensal microbes and harmless antigens. MALT can also communicate with other lymphoid tissues and organs through the circulation of lymphocytes and cytokines. Thus, MALT is a vital component of the mucosal immune system that protects the body from infections and diseases.

NALT is a type of mucosa-associated lymphoid tissue that is found in the nasal cavity and the pharynx. It consists of clusters of lymphoid follicles that are surrounded by a network of T cells, dendritic cells, and macrophages. NALT plays an important role in the immune defense against respiratory pathogens, allergens, and toxins that enter the body through the nose and mouth.

One of the main features of NALT is the presence of specialized epithelial cells called follicle-associated epithelium (FAE), which covers the surface of the lymphoid follicles. FAE contains M cells, which are responsible for sampling antigens from the lumen and delivering them to the underlying antigen-presenting cells (APCs) and lymphocytes. M cells have a unique morphology that allows them to extend microvilli into the lumen and form pockets on the basolateral side where they interact with APCs and lymphocytes.

Another feature of NALT is the formation of germinal centers within the lymphoid follicles. Germinal centers are sites where B cells undergo somatic hypermutation and class switch recombination, resulting in the generation of high-affinity and class-specific antibodies. Germinal centers also contain follicular dendritic cells (FDCs), which trap and display antigens to B cells, and follicular helper T cells (Tfh), which provide signals to B cells for their activation and differentiation.

NALT is involved in both local and systemic immune responses. Locally, NALT produces secretory IgA (sIgA), which is transported across the epithelium and binds to pathogens and toxins in the mucosal surface, preventing their attachment and invasion. Systemically, NALT induces the migration of activated B and T cells to other mucosal sites, such as the lungs, the gut, and the salivary glands, where they can provide protection against similar antigens. NALT also communicates with other lymphoid organs, such as the cervical lymph nodes and the spleen, where it can elicit systemic antibody responses.

NALT is a dynamic and adaptive tissue that can respond to different types of stimuli. For example, NALT can expand or regress depending on the exposure to antigens or inflammation. NALT can also modulate its function depending on the nature of the antigens or signals it receives. For instance, NALT can induce tolerance or immunity depending on whether the antigens are harmless or harmful.

NALT is a key component of the mucosal immune system that protects the upper respiratory tract from various threats. By sampling antigens from the lumen and generating specific immune responses, NALT contributes to the maintenance of mucosal homeostasis and health.

GALT is the largest and most important component of MALT, as it covers about 70% of the total immune system. It consists of lymphoid complexes that are strategically located along the digestive tract, especially in the small intestine and the appendix. These complexes include:

• Peyer`s patches: These are oval-shaped aggregates of lymphoid follicles that are mainly found in the ileum, the last part of the small intestine. They contain B cells, T cells, dendritic cells, and macrophages. They are covered by a specialized epithelium that contains M cells, which are responsible for sampling antigens from the intestinal lumen and delivering them to the underlying immune cells.
• M cells: These are modified epithelial cells that have microfolds on their apical surface, which allow them to take up antigens by endocytosis or phagocytosis. They also have a thin layer of mucus and lack microvilli, which makes them more permeable to antigens. They transport the antigens across their cytoplasm and release them at their basolateral surface, where they encounter antigen-presenting cells (APCs) such as dendritic cells and macrophages. These APCs then process and present the antigens to T cells in the Peyer`s patches or in the mesenteric lymph nodes.
• Intraepithelial lymphocytes (IELs): These are T cells that reside between the epithelial cells of the intestinal mucosa. They can be activated by antigens presented by M cells or by direct contact with microbes. They have cytotoxic and regulatory functions and can secrete cytokines and chemokines that modulate the local immune response.
• Lamina propria lymphocytes (LPLs): These are B cells and T cells that are located in the connective tissue layer beneath the epithelium. They can be activated by antigens presented by APCs or by soluble factors from the lumen. They can differentiate into plasma cells that secrete IgA antibodies, which are transported across the epithelium and bind to microbes in the lumen, preventing their attachment and invasion. They can also migrate to other mucosal sites and provide systemic immunity.

The main function of GALT is to protect the body from pathogens that enter through the oral route, such as bacteria, viruses, parasites, and toxins. It also maintains a balance between tolerance and immunity, as it has to distinguish between harmless commensal microbes and harmful pathogens. It does so by using various mechanisms, such as:

• Oral tolerance: This is a process by which GALT induces a state of unresponsiveness or suppression in immune cells that encounter antigens derived from food or commensal microbes. This prevents unnecessary inflammation and allergic reactions in the gut.
• Immunoglobulin A (IgA): This is the most abundant antibody class in mucosal secretions. It is produced by plasma cells in the lamina propria and transported across the epithelium by a receptor called polymeric immunoglobulin receptor (pIgR). IgA binds to antigens in the lumen and forms immune complexes that are either excreted or taken up by M cells and eliminated by APCs. IgA also neutralizes toxins and viruses and prevents bacterial adhesion and invasion.
• Regulatory T cells (Tregs): These are a subset of T cells that express a marker called CD25 and secrete anti-inflammatory cytokines such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta). They suppress the activation and proliferation of effector T cells and B cells that may cause tissue damage or autoimmunity in the gut.
• Microbiota: These are the diverse communities of microbes that colonize the gut and establish a symbiotic relationship with the host. They contribute to digestion, metabolism, vitamin synthesis, and barrier function. They also modulate the immune system by stimulating IgA production, inducing oral tolerance, competing with pathogens for nutrients and space, producing antimicrobial substances, and influencing gene expression and epigenetic regulation in immune cells.

GALT is essential for maintaining gut health and immunity. However, it can also be involved in various diseases, such as inflammatory bowel disease (IBD), celiac disease, food allergy, infection, cancer, and obesity. Therefore, understanding how GALT functions and interacts with other factors is important for developing new strategies for prevention and treatment of these conditions.

• Peyer’s patches are clusters of lymphoid follicles located in the mucosa and submucosa of the small intestine, especially in the ileum.
• They are part of the gut-associated lymphoid tissue (GALT) and play a role in mucosal immunity and tolerance.
• They contain B cells, T cells, dendritic cells, macrophages and plasma cells that respond to antigens from the intestinal lumen.
• They are covered by a specialized epithelium that contains M cells, which transport antigens from the lumen to the underlying lymphoid tissue.
• They also have germinal centers, where B cells undergo somatic hypermutation and class switch recombination to produce high-affinity IgA antibodies.
• IgA antibodies are secreted into the intestinal lumen through the transcytosis pathway and bind to pathogens and toxins, preventing their attachment and invasion of the mucosal barrier.
• Peyer’s patches also contribute to oral tolerance, which is the suppression of immune responses to harmless antigens ingested through the oral route.
• This is achieved by inducing regulatory T cells (Tregs) that suppress effector T cells and prevent inflammation and tissue damage in the gut.
• Peyer’s patches are important for maintaining a balance between immunity and tolerance in the gut and protecting against intestinal infections.

M cells are specialized epithelial cells that are found in the follicle-associated epithelium of mucosa-associated lymphoid tissues (MALT). They are named after their microfold appearance, which is due to the presence of short and irregular microvilli on their apical surface. M cells have a thin cytoplasm and a large basolateral pocket that contains lymphocytes, macrophages and dendritic cells. These features allow M cells to act as antigen-sampling cells that transport antigens from the mucosal lumen to the underlying lymphoid tissue.

M cells can be divided into two types based on their location and function: intestinal M cells and airway M cells. Intestinal M cells are found in the Peyer`s patches and isolated lymphoid follicles of the small intestine, where they sample antigens from the gut lumen and deliver them to the subepithelial dome region. Airway M cells are found in the nasal-associated lymphoid tissue (NALT) and bronchus-associated lymphoid tissue (BALT), where they sample antigens from the respiratory tract and deliver them to the interfollicular region.

M cells can take up various types of antigens, such as bacteria, viruses, parasites, toxins and food particles, by different mechanisms, such as endocytosis, phagocytosis, transcytosis and receptor-mediated uptake. M cells can also express pattern recognition receptors (PRRs), such as toll-like receptors (TLRs) and nucleotide-binding oligomerization domain-like receptors (NLRs), that can recognize microbial components and trigger innate immune responses. M cells can also express major histocompatibility complex (MHC) class I and II molecules, as well as co-stimulatory molecules, that can present antigens to T cells and initiate adaptive immune responses.

M cells play a crucial role in mucosal immunity by providing a link between the external environment and the mucosal immune system. They can induce both protective and tolerogenic immune responses depending on the nature and dose of the antigen. M cells can also facilitate the generation of secretory IgA antibodies that can neutralize pathogens and toxins at the mucosal surface. However, M cells can also be exploited by some pathogens as a portal of entry into the host. For example, some bacteria, such as Salmonella typhimurium and Shigella flexneri, can invade M cells and cause intestinal infections. Some viruses, such as poliovirus and reovirus, can also infect M cells and spread to other tissues.

M cells are important targets for mucosal vaccine development, as they can induce both systemic and mucosal immune responses. However, there are some challenges in designing effective mucosal vaccines, such as low antigen uptake by M cells, degradation of antigens by proteases and pH changes in the mucosal lumen, lack of adjuvants that can enhance mucosal immunity without causing inflammation or toxicity, and potential induction of oral tolerance or anaphylaxis by some antigens. Therefore, more research is needed to understand the biology and function of M cells and to develop novel strategies to modulate their activity for mucosal immunization.

• BALT is a type of MALT that is found in the respiratory tract, especially in the lungs and bronchi.
• BALT consists of clusters of lymphoid cells that form follicles or nodules under the mucosal epithelium of the airways.
• BALT follicles contain mostly B cells that produce antibodies, especially IgA, against inhaled antigens. They also have germinal centers where B cells undergo somatic hypermutation and class switch recombination to generate high-affinity and diverse antibodies.
• BALT also contains T cells, dendritic cells, macrophages, and plasma cells that participate in antigen presentation and immune activation.
• BALT is not present at birth, but develops in response to environmental stimuli such as microbial exposure, inflammation, or allergens.
• BALT plays a crucial role in mucosal immunity by providing a first line of defense against respiratory pathogens and by inducing local and systemic immune responses.
• BALT also contributes to immune tolerance by regulating the balance between pro-inflammatory and anti-inflammatory cytokines and by inducing regulatory T cells that suppress excessive or harmful immune reactions.

The mucosa-associated lymphoid tissue (MALT) initiates immune responses to specific antigens encountered along all mucosal surfaces. Mucosal surfaces are the first line of defense against pathogens and foreign substances that enter the body through the respiratory, digestive, and genitourinary tracts. MALT tissues comprise the mucosal immune system, which can function independently of the systemic immune system and are, therefore, an important aspect of immunity.

MALT has several functions that contribute to the protection of the mucosal surfaces and the maintenance of homeostasis. Some of these functions are:

• IgA production and transport: IgA is the most abundant immunoglobulin in mucosal secretions and plays a key role in preventing the attachment and invasion of pathogens to the epithelial cells. IgA is produced by plasma cells that originate from B cells activated in MALT follicles. IgA is then transported across the epithelium by specialized receptors called polymeric immunoglobulin receptors (pIgR) and released into the lumen as secretory IgA (sIgA). sIgA can bind to antigens and neutralize them or facilitate their clearance by mucociliary action or peristalsis.
• Antigen sampling and presentation: MALT contains specialized epithelial cells called M cells that are located in the follicle-associated epithelium (FAE) overlying the lymphoid follicles. M cells can take up antigens from the lumen by endocytosis or phagocytosis and deliver them to the underlying antigen-presenting cells (APCs), such as dendritic cells and macrophages. These APCs then process and present the antigens in the context of major histocompatibility complex (MHC) molecules to T cells, which are located in the interfollicular regions and the subepithelial dome regions of MALT. The T cells can then activate B cells or other effector cells to mount an immune response against the antigens.
• Lymphocyte homing and migration: MALT is connected to other mucosal sites and to the systemic immune system by a network of lymphatic vessels and blood vessels. The lymphocytes that are activated in MALT can migrate to other parts of the mucosal immune system or to the systemic circulation by following specific homing signals. These signals are provided by adhesion molecules and chemokines that are expressed by endothelial cells and stromal cells in different tissues. For example, B cells activated in Peyer`s patches can express a receptor called α4β7 integrin, which binds to an adhesion molecule called mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) expressed by endothelial cells in the lamina propria of the gut. This allows the B cells to home to the gut and secrete IgA there. Similarly, T cells activated in NALT can express a receptor called CC chemokine receptor 7 (CCR7), which binds to a chemokine called CCL21 expressed by stromal cells in the lymph nodes. This allows the T cells to home to the lymph nodes and participate in systemic immunity.
• Tolerance induction: MALT also plays a role in inducing tolerance to harmless antigens, such as food antigens and commensal bacteria, that are constantly present in the mucosal surfaces. Tolerance is a state of unresponsiveness or non-reactivity of the immune system to a specific antigen. Tolerance can be achieved by several mechanisms, such as deletion, anergy, or regulation of lymphocytes that recognize self or harmless antigens. MALT contains regulatory T cells (Tregs) that can suppress the activation and proliferation of other T cells that may react to harmless antigens. MALT also contains dendritic cells that can induce tolerance by presenting antigens in a low dose or without co-stimulatory signals, which can result in anergy or deletion of antigen-specific T cells.

In summary, MALT is a vital component of the mucosal immune system that performs various functions to protect the mucosal surfaces from pathogens and foreign substances, while maintaining tolerance to harmless antigens. MALT is composed of different types of lymphoid tissues that are strategically located at different sites along the mucosal surfaces, such as NALT, GALT, BALT, etc. These tissues share a common structure and function but also have some unique features that reflect their specific location and role.

Mucosa-associated lymphoid tissues (MALT) are specialized structures that provide immune protection to the mucosal surfaces of the body. They are composed of lymphoid follicles, interfollicular regions, subepithelial dome regions, and follicle-associated epithelium. They are found in various locations such as the nasal passages, the gut, and the bronchi. They have a common function of sampling antigens from the lumen and presenting them to antigen-presenting cells and lymphocytes. They also facilitate the migration of activated T and B cells to other mucosal sites and the secretion of IgA antibodies across the epithelium. MALT tissues are essential for maintaining mucosal immunity and preventing infections by pathogens that enter through the mucosal routes.

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