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Further information: Immunity

Immunity system would protect animals from the threat of viruses, but, the different parts of the immunity system would be available for particular tissue or organ. The local immunity system is not the same as the body systemic immunity, it is a natural or acquired immunity which is limited to a particular tissue or organ. The migration of memory T cells is basic local immunity, at the same time, the immunity function relies on long-living memory T cells, the memory subsets contribute to the immunity system.

Local Immunity of Lung

Primary small airway epithelial cells

There are about 10-20000 Lairs per day that are ventilated through the surface of lung mammals. Therefore, the lung is the largest organ of human which directly contact with the atmospheric environment. Although most of the airborne microbial compounds do not be harmful to humans, some of them might be harmful. Innate sensor functions of the lung are natural, which could detect the danger of microbial compounds. The local immunity function of lung could help the body to avoid inflammation. As for the airway epithelial cells, they are vital regulators for immunoreaction in the lung. To prevent the infection, a human's lung has some specialized cells of the immune system such as alveolar macrophages and dendritic cells, those cells could kill pathogens and make an inflammatory response for protection. For airway epithelial cells, the most significant purpose is that regulating the sensibility of immune sensing.

Lung immunity about children （allergies and asthma）

For children, early exposure to microorganisms in the living environment can activate the innate immune system and regulate immune responses earlier, which can help prevent asthma and allergic reactions. When children suffer from respiratory allergies and asthma, their upper and lower respiratory tracts will produce corresponding symptoms. It is worth mentioning that when children inhale allergens, the airway epithelium is the first site of contact with allergens. Base cells, ciliated cells, goblet cells, and other cells constitute the airway epithelium. Because airway epithelial cells have a strong anti-microbial capacity, airway epithelial cells participate in host resistance to inflammation and immunity, at the same time, it also acts as a physical barrier to selectively screen lung inhalation components to prevent harmful components from entering the body. Airway epithelial cells make Th2 immunity and tolerance work better in allergies and asthma by regulating and activating more immune cells such as dendritic cells (DC). There is no doubt that a complete physical barrier layer can effectively reduce allergens entering the body, and it can help enhance the protective innate immune response. Asthma and allergies can lead to mutations in some genes, and some genes can also help epithelial cells establish a complete barrier function. At the same time, some endogenous factors such as smoke, air pollution, and inflammation also enhance or weaken the barrier function of epithelial cells. So genes and environment have a great influence on the immunity of epithelial cells. A complete pulmonary epithelial cell barrier can inhibit allergens and harmful microorganisms and maintain local immune balance. For children, early environmental factors may have protective or destructive effects on their lung barrier. If some children live in places where air pollution is more serious since childhood, leading to pathogenic bacteria in their lungs, and the diversity of intestinal microflora in early childhood is less, these can become triggers for asthma and allergies. Epithelial barrier function and the development of the immune system play an important role in the development of allergy and asthma. At the same time, genetic material, environment, dietary habits and exposure to microorganisms will also affect the development of the immune system and normal work. Factors affecting asthma and allergies include the way of delivery and a written diet. For newborns, changes in Microbiology and living conditions can affect asthma and allergies.

Respiratory Tract Infection and the Role of Respiratory Tract Microorganisms

The use of high-throughput sequencing methods proves that the lungs are not sterile, and the imbalance between the presence of respiratory microorganisms and the host is an important factor leading to illness. Early respiratory tract infections and asthma have a certain degree of correlation with a respiratory syncytial virus (RSV) and rhinovirus (RV), moreover these viruses also directly attack the airway epithelium, because the human body's antiviral response is weakened, so the airway epithelium of asthmatic patients is more vulnerable to RV. Overall, respiratory viruses interact with bacteria, which can be a trigger for respiratory inflammation, asthma, and allergies. Moreover, the infection may weaken the barrier function of airway epithelium and decrease the local immunity of lungs, thus weakening the screening function of allergens entering the lungs.

The role of intestinal microbiome and dietary effects

It is certain that some interactions between airway epithelium and microflora will affect the health of the lungs. At the same time, some interactions between microflora and intestinal tract and skin will also have some effects. The interaction between intestinal microflora and the intestinal mucosal immune system has a certain influence on the immune system. When the body begins to use antibiotics too much from an early age, it will lead to immune disorders and increase the likelihood of allergies and asthma. Some children with 17q21 chromosome mutation may develop asthma by impairing their antiviral immunity. Fungi, viruses, bacteria, and parasites make up the intestinal microbial community. When the proportion of intestinal microbial community changes, it may eventually affect the immune system. For example, worms in intestinal microorganisms can ensure the diversity of intestinal bacteria and protect against allergic airway inflammation. The metabolite SCFAs produced by intestinal bacteria provide energy for body cells and bacteria themselves. The regulation of diet and food intake determine its production. A significant role of SCFAs is that it enhances the barrier capacity of the intestinal epithelium. For newborns, carbohydrate fibers and fatty acids in breast milk are difficult to absorb, which can inhibit the formation of intestinal function. Drinking unprocessed farm milk may promote more Treg cells in newborns within one year of age. In summary, the diversity of intestinal microorganisms plays an important role in the formation of the immune system and the development of mucosa and plays a positive role in resisting allergic reactions.

Environmental microbial exposure

For the immature immune system, the exposure of environmental microorganisms will regulate the development of the immune response to prevent some diseases. For some children growing up in farm families, they may have a strong immunity to allergies and asthma because they live near animal shelters with Gram-negative bacteria and fungi that may affect airway epithelial barriers.  For children, the way they are born also affects their immune system. For babies with the ruptured abdomen, they are more likely to suffer from allergies and asthma than babies with vaginal delivery. Babies born to the latter activate their immune system earlier. At the same time, the infant's gestational age also affects the development of the immune system.

overall

• Complete lung barrier is a key factor in preventing allergic diseases and asthma.

• Exposure to a large number of pathogens and contaminated environment will impair lung barrier function.

• Microorganisms exposed in some farms play an active role in local immunity and barrier function.

• Microorganisms in the intestine also affect the immune system in the lungs.

• Difficult carbohydrates and fibers can affect lung immunity.

Airway epithelial cells

The microbial products would be separated from the body by the epithelial cells , which could limit microbial access to immune sensors. Also it could be regarded as a physical barrier for lung. The intercellular connections are tight, which can prevent water, ions' paracellular transport.  In order to make the physical barrier stronger, goblet cells are scattered in the epithelial or submucosal glands of the airway. They secrete mucus into the airway lumen to form a mucus protective layer. There are at least 16 kinds of mucin that are a high molecular weight glycoprotein which has been observed in the lung (MUC1MUC13, and MUC22). The primary function of protective mucus produced by mucin is to create a barrier to block inhaled particles, which are then transported out of the respiratory tract by MCC. In addition, mucin also exhibits antimicrobial, antiprotease, and antioxidant activity, which contributes to nonspecific, innate immune defenses. If the MCC does not work, the mucus would be accumulated in the lungs which leads to the inflammation of the chronic airway. MUC1 is a very useful immunomodulatory mucin, it is appeared in goblet cells as well as in lymphocytes and dendritic cells. In addition to cell-cell contact, immunomodulatory activity was also identified in the supernatant of epithelial cells. In addition, molecules that mediate cell-matrix interactions such as V 6-integrins have immunomodulatory properties. One feature of some lung pathogens is their ability to lead the cell to death in airway epithelial cells. Therefore, incomplete epithelial cells will impair the above-mentioned immunomodulatory substances and physical barrier functions. Thus, Microbial virulence factors cause inflammation that destroys barrier cells and epithelial integrity, leading to inhibition of release.

Function of mucin

The main regulators of airway and lung homeostasis and inflammation are airway epithelial cells. When those mechanisms disorders, which leads to a variety of chronic inflammatory diseases. Five different mucin gene products make up two layers of mucin in the airway surface fluid. In addition, the outer layer contains two gel-forming gelatins, including MUC5AC and MUC5B. They are isolated from the apical cell surface and they are closely related to various bioactive defense molecules, while the inner layer contains three MUC1, MUC4, and MUC16 mucus. When the airway is infected, this mucus becomes the primary defense against pathogens. MUC1 mucin is produced by columnar epithelial cells on the surface of the respiratory tract and types II alveolar cells in the alveoli, which can prevent the development of inflammatory lung disease by eliminating inflammation. It is worth mentioning that this mucus is indispensable in respiratory infections.

Ectopic lymphoid tissues and local immunity

The secondary lymphatic organ is an important part of the immune system. Naive lymphocytes could be recruited from the blood by each secondary lymphoid organ and it activated anti-presenting cells from surrounding tissues. At the same time, in order to effectively produce a rapid and robust adaptive immune response, hence every special secondary lymphatic organ has evolved to maximize. The development of many mucosal lymphoid is pre-programmed and it does not require pathogen result in inflammation or another type of adaptive immune response.

The development of ectopic lymphoid tissues would happen to respond to autoimmunity for adults, chronic inflammation and infection. These tissues develop in almost every body’s organ and do not appear in predictable places. Second and third lymphoid tissues are involved to some extent in the immune response, but ectopic follicles are mainly associated with pathology and harmful autoimmune responses, and these tissues may also be involved in the protective immune response to local infections. For the organogenesis of LNs and Peyer's patches, LTi cells are necessary. However, the statement that LTi cells are essential to forming ectopic follicles is yet to be confirmed. The development of these tissues usually happens in adults to respond to chronic inflammation and chronic infection is one of the reasons that LTi cells are not compulsory for ectopic lymphoid tissues to develop. Meanwhile, as people get older, they usually have a broader range for circulating greater developed lymphocytes that secrete LTαβ, especially while activated, the duty of LTi cells are able to be achieved through lymphocytes activation. Level III lymphoid organs are usually developed in autoimmune diseases, as well as, it is more likely to present in the organ which is attacked by autoimmunity, such as the lungs of rheumatoid arthritis patients. There are some other studies have proposed that lymphogenesis is unnecessarily associated with activity or severity of arthritis, however, it has an association with local autoantibody production and higher titer of antinuclear antibodies. As well as the autoantibodies, which are produced locally, will be increased for patients who have pulmonary manifestations of rheumatoid arthritis and Sjogren's syndrome.