Mucosa Associated Lymphoid Tissues (MALT)

What is Mucosa Associated Lymphoid Tissues (MALT)?

• The mucous membranes lining the digestive, respiratory, and urogenital systems have a total surface area of around 400 m2 (almost the size of a basketball court) and are the primary entrance points for the majority of infections.
• These sensitive membrane surfaces are protected by the previously stated collection of organised lymphoid tissues known together as mucosal-associated lymphoid tissue (MALT).
• These tissues range from loose, poorly organised lymphoid cell clusters in the lamina propria of intestinal villi to well-organized structures such as the tonsils, appendix, and Peyer’s patches, which are located in the submucosal layer of the intestinal lining.
• MALT’s massive population of antibody-producing plasma cells, whose number considerably exceeds that of plasma cells in the spleen, lymph nodes, and bone marrow combined, attests to its functional significance in the body’s immune system.
• There are three places for the tonsils: lingual at the base of the tongue, palatine at the sides of the rear of the mouth, and pharyngeal (adenoids) at the roof of the nasopharynx.
• All three tonsil groups are nodular formations composed of reticular cells, fibres, lymphocytes, macrophages, granulocytes, and mast cells.
• The B cells are arranged into follicles and germinal centres, which are bordered by T-cell-active areas. Antigens entering via the nasal and oral epithelial pathways are defended against by the tonsils.
• The mucous membrane lining the digestive tract has been the subject of extensive research. As with the respiratory and urogenital tracts, this tissue has the ability to endocytose antigen from the lumen.
• Against pathogens, immune reactions are activated, and antibodies can be produced and transferred to the lumen to resist the invading organisms.
• In numerous locations of this tissue, lymphoid cells can be detected. The mucosal epithe lial layer’s outermost layer contains intraepithelial lymphocytes (IELs). Numerous of these lymphocytes are T cells with uncommon antigen-binding receptors (T-cell receptors, or TCRs), which demonstrate low antigen variety.
• Despite the fact that this population of T cells is well-positioned to encounter antigens that enter through the intestinal mucous epithelium, their true function is poorly unclear. Under the epithelial layer, the lamina propria contains many B cells, plasma cells, activated TH cells, and macrophages in loose clusters.
• In the intestinal lamina propria of a healthy infant, histological sections have revealed more than 15,000 lymphoid follicles.
• Peyer’s patches, nodules of 30–40 lymphoid follicles, are located in the submucosal layer under the lamina propria.
• Peyer’s patches lymphoid follicles, like lymphoid follicles at other places, can grow into secondary follicles with germinal centres. By conveying small samples of foreign antigen from the lumina of the respiratory, digestive, and urogenital tracts to the underlying mucosal-associated lymphoid tissue, the epithelial cells of mucous membranes play an important role in stimulating the immune response.
• This transport of antigen is performed by specialised M cells. These flattened epithelial cells lack the microvilli that are characteristic of the remainder of the mucous epithelium.
• Moreover, M cells have a deep invagination or pocket in the basolateral plasma membrane; this pocket contains a cluster of B cells, T cells, and macrophages. Antigens on the luminal membrane are endocytosed into vesicles that are transferred to the underlying pocket membrane.
• The vesicles subsequently fuse with the membrane of the pocket, delivering the possibly response-activating antigens to the lymphocyte clusters within the pocket. M cells reside in so-called inductive sites, which are tiny patches of a mucous membrane that lie over lymphoid follicles.
• Within these lymphoid follicles, antigens delivered across the mucosal membrane by M cells can activate B cells. The activated B cells develop into plasma cells, which exit the follicles and produce IgA-class antibodies.
• The antibodies are subsequently carried across the epithelial cells and discharged into the lumen as secretory IgA, where they can interact with antigens. Mucous membranes are an effective barrier against the entrance of the majority of infections, contributing to nonspecific immunity.
• This is due, in part, to the mucosal epithelial cells’ tight connections, which make pathogen penetration difficult. Some enteric pathogens, including bacteria and viruses, have utilised the M cell as an entry point via the mucous-membrane barrier, which is quite interesting.
• In some instances, the M cell internalises the pathogen and transports it to the pocket. In other instances, the pathogen binds to the M cell and destroys it, so permitting its access. Several invasive Salmonella species, Vibrio cholerae, and the polio virus are among the pathogens that exploit M cells in this manner.

Features of Mucosa Associated Lymphoid Tissues (MALT)

• About half of the immune system’s lymphocytes reside in the Mucosa-associated lymphoid tissue (MALT). MALT is located along the mucosal tissue surfaces of all mucosal tissues.
• However, conjunctiva-associated lymphoid tissue (CALT), lacrimal duct-associated (LDALT), larynx-associated (LALT), and salivary duct-associated lymphoid tissue (DALT) have also been discovered.
• MALT’s primary purpose is to generate and secrete IgA across mucosal surfaces during antigen-specific, Th2-dependent reactions; however, Th1 and cytotoxic T-cell-mediated reactions are also possible, with the latter leading in immunotolerance.
• Functionally, MALT can be separated into effector sites and inductive sites. Inductive sites include GALT, BALT, and NALT, CALT in mice, dogs, and baboons, and DALT in cynomolgus macaques.

Gut-Associated Lymphoid Tissue (GALT)

• As part of the immune system’s mucosa-associated lymphoid tissue (MALT), gut-associated lymphoid tissue (GALT) helps to ward off invaders in the digestive tract.
• The mucosal surface is thin and acts as a permeable barrier to the internal body due to its physiological function in food absorption.
• Its porous and easily penetrated nature also makes it susceptible to infection; this is the primary entry point for most pathogens into the human body.
• GALT’s high population of plasma cells, which are antibody makers, is greater than that of the spleen, lymph nodes, and bone marrow combined, and this is what gives GALT its functional relevance in the body’s defence.
• Since GALT accounts for over 70% of the total immune system mass, its impairment may have far-reaching effects on immunological function.

Structure of Gut-Associated Lymphoid Tissue (GALT)

• The lymphoid tissue associated with the gastrointestinal tract is distributed throughout the intestine, covering an area of 260–300 m2.
• The intestinal mucosa is composed of finger-like projections (villi) coated by a monolayer of epithelial cells, which separates the GALT from the lumen intestine and its contents.
• On their luminal surface, these epithelial cells have a coating of glycocalyx to protect them from the acidic pH.
• Constant production of new epithelial cells derived from stem cells at the base of the intestinal glands regenerates the epithelium (epithelial cell turnover time is less than one week).
• Although typical enterocytes are the predominant cell type in these crypts, Paneth cells are also present.
• These are found at the bottom of the crypts and emit a variety of antibacterial chemicals, including lysozyme; they are believed to have a role in the control of infections.
• Lamina propria is an underlying layer of loose connective tissue that lies beneath them.
• Additionally, there is lymphatic circulation in the connective tissue of the mesenteric lymph nodes.
• Due to the presence of immune cells through the epithelial cells and lamina propria, both GALT and mesenteric lymph nodes are places where the immune response is initiated.
• Human Peyer’s patches, isolated lymphoid follicles distributed throughout the intestine, and the appendix are also included in the GALT.
• GALT can also be split into two groups based on its structure, from which its functions emerge. One can discover 1.) GALT composed of folicules, including Peyer’s patches, mesenteric lymph nodes, and an even more organised appendix. Its primary role is to provoke an immunological response. 2.) diffuse GALT characterised by solitary T and B cells, macrophages, eosinophils, basophils, and mast cells, which are primarily present in the lamina propria. This portion of GALT is composed of mature effector cells that are prepared to perform their functions.

What are Peyer’s patches?

• Peyer’s patch is a collection of lymphoid cells protruding into the lumen of the gut that plays a crucial role in the initiation of the immune response.
• It produces a subepithelial dome in which a significant number of B cell follicles with their germinal centres, T cell regions in a smaller number, and dendritic cells are located.
• In this region, the subepithelial dome and intestinal lumen are separated by a layer of follicle-associated epithelium.
• This contains ordinary intestinal epithelial cells and a limited number of microfold cells (M cells), which are specialised epithelial cells.
• These M cells, unlike enterocytes, have a folded luminal surface instead of microvilli, do not emit digestive enzymes or mucus, and lack a thick surface of glycocalix, allowing them to come into contact with microbiota and antigens found in the content of the gut.

Functions of GALT

• The intestine and gut-associated lymphoid tissue (GALT) are crucial components of the body’s immune defence, shielding it from external antigens and pathogens while tolerating commensal bacteria and food antigens.

Nasopharynx-Associated Lymphoid Tissue (NALT)

• In animals, nasal- or nasopharynx-associated lymphoid tissue (NALT) represents the nasal mucosa’s immune system and is a component of mucosa-associated lymphoid tissue (MALT).
• NALT is made of paired lymphoid aggregates in the caudoventral section of the left and right nasal passageways near the entry of the nasopharyngeal duct in rats, mice, hamsters, and non-human primates.
• NALT formation begins shortly after birth; it is absent during embryogenesis and in newborn mice. One week after birth, the first symptoms of NALT (HEV with accompanying lymphocytes) appear, although complete development occurs between 5 and 8 weeks later.
• NALT development, unlike Peyer’s patches and lymph nodes, is independent of IL-7R, LT-βR, and ROR-γ signalling.
• It requires the Id2 gene, which induces CD3CD4+CD45+ cell development. After birth, these cells aggregate at the site of NALT and stimulate its development.
• It defends the body against airborne viruses and other pathogens.
• In humans, NALT has been compared to Waldeyer’s ring.

Structure of Nasopharynx-Associated Lymphoid Tissue (NALT)

• NALT is positioned on the cartilaginous soft palate of the upper jaw, bilaterally on the posterior side of the palate, in mice.
• It is mostly composed of lymphocytes, T cell and B cell enriched zones, follicle-associated epithelium (FAE) with epithelial M cells and a small number of erythrocytes. M cells often absorb antigens from mucosa.
• In certain regions of NALT, lymphatic vessels and HEVs are present (high endothelial venule). There are also dendritic cells and macrophages present.
• NALT has almost the same number of T and B lymphocytes. There are approximately 3–4 times more CD4+ T cells than CD8+ T cells in the T-cell population.
• Few T cells have the αβ T cell receptor (TCR), while the majority have the γδ TCR. CD4+ T lymphocytes are in a naive condition, as indicated by their strong CD45RB expression. B cells are predominantly in an unswitched condition, with a phenotype of sIgM+ IgD+.

Functions of NALT

• NALT in mice has a strategic position for invading infections and is the initial site of pathogen detection and clearance. It has a crucial function in eliciting mucosal and systemic immune responses. Similar to Peyer’s patches in the small intestine, NALT is an inductive location for MALT.
• NALT lymphocytes proliferate and differentiate upon intranasal immunisation or pathogen detection. They begin producing cytokines including IFN-γ, type I interferons, IL-2, IL-4, IL-5, IL-6, and IL-10 (amount depend on used immunizating agent or adjuvans). 
• Isotype switching occurs in B lymphocytes, which produce antigen-specific IgM, IgG, and primarily IgA. Because they carry chemokine receptors CCR10 and α4β1 integrin, activated B cells can move through the body to the respiratory and genitourinary tracts. After vaccination, memory T and B cells are formed and persist for a long period.

Bronchus-Associated Lymphoid Tissue (BALT)

• BALT is tertiary lymphoid tissue. Lung and bronchus lymphoid follicles are part of mucosa-associated lymphoid tissue (MALT).
• BALT is an efficient mucosal and systemic immune response priming location.
• There is an abundance of species diversity in BALT. BALT is typically lacking in canines, felines, and Syrian hamsters. In terms of the amount of BALT sites, rabbits have the most, followed by rats, guinea pigs, and mice.
• Germ-free pigs lack BALT, whereas germ-free rats possess BALT, albeit to a considerably lesser extent than their traditionally raised counterparts. The issue with mice (and people) is more contentious.

Structure of Bronchus-Associated Lymphoid Tissue (BALT)

• BALT is comparable in most mammalian species, although its maintenance and inducibility vary. While it is a typical component of the lungs and bronchus in rabbits and swine, it only manifests in mice and humans following infection or inflammation.
• Thus, in mice and humans, it is known as inducible BALT (iBALT). BALT and iBALT are physically and functionally very similar; hence, only BALT is used to refer to both structures in this article.
• BALT is located along the bifurcations of the upper bronchi, immediately under the epithelium, and often between an artery and a bronchus.
• It is also present in perivascular, peribronchial, and even interstitial regions of the lung’s lower airways.
• To qualify as BALT, a mass of lymphocytes and other immune cells must be organised. There are lymphoid follicles with obvious germinal centres and the majority of B-cells encircled by T-cell area.
• In the interfollicular T-cell region, many dendritic cells provide antigen to T-cells, whereas germinal centres include follicular dendritic cells.
• Germinal centres and interfollicular area include CD4+ Th lymphocytes, whereas interfollicular area contains the majority of CD8+ T cells.
• High endothelial venules (HEVs) are also found in the T/B-cell interface of BALT, enabling the recruitment of naive T cells.
• These HEV are the only entry point for lymphocytes migrating into the BALT, which they thereafter exit by efferent lymphatic veins.
• Similar to M cells in the dome epithelium of Peyer’s patches, M cells have been described in the epithelium above BALT in some species, however the dome epithelium is not typical for BALT.
• BALT creation in mice is dependent on inteleukin-17, VCAM-1, PNAd, and LFA-1, but not on lymphotoxin-α, although the establishment of secondary lymphoid organs (such as lymph nodes and Peyer’s patches) is normally dependent on LTα.
• Disabled in situ Treg cell function may contribute to the development of BALT.

Function of Bronchus-Associated Lymphoid Tissue (BALT)

• BALT’s function and purpose are still unknown. It is also unknown if its production is a natural aspect of the immune response or whether it is pathological and should be repressed.
• BALT contributes to the efficient priming of adaptive B-cell and T-cell responses to airborne antigens. Dendritic cells are necessary for its preservation and function. Inducible BALT is produced in response to infection, such as influenza, and reaches its maximum size between 1 and 2 weeks after infection before declining.
• Due to the time required to generate iBALT, immunological responses beginning in iBALT are delayed relative to the immune response in the draining lymph nodes.
• However, iBALT may be a component of the pathophysiology in chronic diseases. BALT can be induced even after chorioamnionitis or intrauterine pneumonia in foetal lungs.
• BALT can also develop in response to other stimuli, such as inflammation induced by rheumatoid arthritis or another autoimmune lung illness, or mechanical injury caused by dust particles.

References

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