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. [1] It protects body from airborne viruses and other infectious agents. In humans, NALT is considered analogous to Waldeyer's ring. [2]
NALT in mice is localized on cartilaginous soft palate of upper jaw, it is situated bilaterally on the posterior side of the palate. It consists mainly of lymphocytes, T cell and B cell enriched zones, follicle-associated epithelium (FAE) with epithelial M cells and some erythrocytes. M cells are typical for antigen intake from mucosa. In some areas of NALT, there are lymphatic vessels and HEVs (high endothelial venule). Dendritic cells and macrophages are also present.
NALT contains about same amount of T cells and B cells. The T-cell population contains about 3–4 times more CD4+ T cells than CD8+ T cells. Most of T cells are with αβ T cell receptor (TCR) and only few are with γδ TCR. CD4+ T cells are in naive state, marked by high expression of CD45RB. B cells are mostly in unswitched state, with sIgM+ IgD+ phenotype. [3] [4]
Formation of NALT starts early after birth, it is not present during embrygenesis or in newborn mice. First signs of NALT (HEV with associated lymphocytes) occurs one week after birth, but full formation is established after 5–8 weeks. In contrast to Peyer's patches and lymph nodes, NALT formation is independent of IL-7R, LT-βR and ROR-γ signalling. It requires Id2 gene, which induce genesis of CD3−CD4+CD45+ cells. These cells accumulates on the site of NALT after birth and induce NALT formation. [4]
NALT in mice has strategic position for incoming pathogens and it is the first site of recognition and elimination of inhaled pathogens. It has a key role in inducing mucosal and systemic immune response. NALT is inductive site of MALT similarly to Peyer's patches in a small intestine.
After intranasal immunization or pathogen recognition, lymphocytes in NALT proliferate and differentiate. They start to produce cytokines, such as IFN-γ, type I interferons, IL-2, IL-4, IL-5, IL-6 or IL-10 (amount depend on used immunizating agent or adjuvans). B cells go through isotype switching and produce antigen-specific IgM, IgG and mainly IgA. Activated B cells can migrate through body to respiratory and genito-uritary tract, because they express chemokine receptors CCR10 and α4β1-integrin. Memory T and B cells are established and last for long time after immunization. [4] [5] [6]
Intranasal (i.n.) immunization or vaccination is an effective way to stimulate respiratory immune system. This way of immunization can provoke both the cell-mediated and humoral immune responses and is capable of stimulating both the mucosal and systemic immune systems. A dose of i.n. administered antigen can be much smaller than of oral administered antigen, because antigens are not exposed to digestive enzymes. Thus, it would be a suitable way of vaccination against airborne viruses and bacteria. In 1997, nasal-spray vaccine containing inactivated influenza virus with nLT (heat-labile enterotoxin) as adjuvants was used in Switzerland, but it had to be withdrawn from the market, because it caused Bell's palsy in some patients. [7] Thus, scientists are looking for more suitable and safe adjuvants, for expamle, Masafumi Yamamoto et al. in 1998 on mice model proved safe and efficient i.n. vaccination against Streptococcus pneumoniae [8] and in 2002 also against influenza virus. [9]
A DNA vaccine is a type of vaccine that transfects a specific antigen-coding DNA sequence into the cells of an organism as a mechanism to induce an immune response.
Cell-mediated immunity or cellular immunity is an immune response that does not involve antibodies. Rather, cell-mediated immunity is the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen.
Plasma cells, also called plasma B cells or effector B cells, are white blood cells that originate in the lymphoid organs as B cells and secrete large quantities of proteins called antibodies in response to being presented specific substances called antigens. These antibodies are transported from the plasma cells by the blood plasma and the lymphatic system to the site of the target antigen, where they initiate its neutralization or destruction. B cells differentiate into plasma cells that produce antibody molecules closely modeled after the receptors of the precursor B cell.
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.
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.
Intraepithelial lymphocytes (IEL) are lymphocytes found in the epithelial layer of mammalian mucosal linings, such as the gastrointestinal (GI) tract and reproductive tract. However, unlike other T cells, IELs do not need priming. Upon encountering antigens, they immediately release cytokines and cause killing of infected target cells. In the GI tract, they are components of gut-associated lymphoid tissue (GALT).
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.
Marginal-zone B cells are noncirculating mature B cells that in humans segregate anatomically into the marginal zone (MZ) of the spleen and certain other types of lymphoid tissue. The MZ B cells within this region typically express low-affinity polyreactive B-cell receptors (BCR), high levels of IgM, Toll-like receptors (TLRs), CD21, CD1, CD9, CD27 with low to negligible levels of secreted-IgD, CD23, CD5, and CD11b that help to distinguish them phenotypically from follicular (FO) B cells and B1 B cells.
T helper 3 cells (Th3) are a subset of T lymphocytes with immunoregulary and immunosuppressive functions, that can be induced by administration of foreign oral antigen. Th3 cells act mainly through the secretion of anti-inflammatory cytokine transforming growth factor beta (TGF-β). Th3 have been described both in mice and human as CD4+FOXP3− regulatory T cells. Th3 cells were first described in research focusing on oral tolerance in the experimental autoimmune encephalitis (EAE) mouse model and later described as CD4+CD25−FOXP3−LAP+ cells, that can be induced in the gut by oral antigen through T cell receptor (TCR) signalling.
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.
Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells, derived from common lymphoid progenitors (CLPs). In response to pathogenic tissue damage, ILCs contribute to immunity via the secretion of signalling molecules, and the regulation of both innate and adaptive immune cells. ILCs are primarily tissue resident cells, found in both lymphoid, and non- lymphoid tissues, and rarely in the blood. They are particularly abundant at mucosal surfaces, playing a key role in mucosal immunity and homeostasis. Characteristics allowing their differentiation from other immune cells include the regular lymphoid morphology, absence of rearranged antigen receptors found on T cells and B cells, and phenotypic markers usually present on myeloid or dendritic cells.
The avian immune system is the system of biological structures and cellular processes that protects birds from disease.
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.
ILC2 cells, or type 2 innate lymphoid cells are a type of innate lymphoid cell. Not to be confused with the ILC. They are derived from common lymphoid progenitor and belong to the lymphoid lineage. These cells lack antigen specific B or T cell receptor because of the lack of recombination activating gene. ILC2s produce type 2 cytokines and are involved in responses to helminths, allergens, some viruses, such as influenza virus and cancer.
Tissue-resident memory T cells or TRM cells represent a subset of a long-lived memory T cells that occupies epithelial, mucosal and other tissues without recirculating. TRM cells are transcriptionally, phenotypically and functionally distinct from central memory (TCM) and effector memory (TEM) T cells which recirculate between blood, the T cell zones of secondary lymphoid organ, lymph and nonlymphoid tissues. Moreover, TRM cells themself represent a diverse populations because of the specializations for the resident tissues. The main role of TRM cells is to provide superior protection against infection in extralymphoid tissues.
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.
A nasal vaccine is a vaccine administered through the nose that stimulates an immune response without an injection. It induces immunity through the inner surface of the nose, a surface that naturally comes in contact with many airborne microbes. Nasal vaccines are emerging as an alternative to injectable vaccines because they do not use needles and can be introduced through the mucosal route. Nasal vaccines can be delivered through nasal sprays to prevent respiratory infections, such as influenza.
Integrin α4β7 is an integrin heterodimer composed of CD49d (alpha-4) subunit and beta-7 subunit noncovalently linked. LPAM-1 is expressed on the cell surface of leukocytes. This receptor is involved in lymphocyte trafficking pathway to site of inflammation in intestinal tissues.
Whole-cell vaccines are a type of vaccine that has been prepared in the laboratory from entire cells. Such vaccines simultaneously contain multiple antigens to activate the immune system. They induce antigen-specific T-cell responses.