Research Area

Immune System Development

Immune system development overview

The immune system has the function of immune surveillance, defense, and regulation. This system consists of immune organs (bone marrow, spleen, lymph nodes, tonsils, small intestine collecting lymph nodes, appendix, thymus, etc.), immune cells (lymphocytes, mononuclear phagocytic cells, neutrophils, basophils, eosinophils, Mast cells, platelets (because of IgG in platelets), and immunologically active substances (antibody, lysozyme, complement, immunoglobulin, interferon, interleukin, tumor necrosis factor and other cytokines). The immune system is divided into innate immunity (also known as non-specific immunity) and adaptive immunity (also known as specific immunity), wherein adaptive immunity is divided into humoral immunity and cellular immunity. The development of the immune system is essential for the normal growth of the body. If the immune system is not properly developed, it will induce related diseases.

Immune system development research status

The basic function of the immune system is to identify self and non-self while generating different response strategies. According to current understanding, the evolution of the immune system can be roughly divided into five levels. The first level is characterized by the specific aggregation of the same species to compete for survival, and found in plants, cavernous, protozoa, etc.; the second level is characterized by specific differentiated immune cell-mediated non-memory immune recognition and immunity reactions, such as coelenterates; the third level is cell-mediated immunity with short-term memory function, such as annelids, arthropods, echinoderms, etc.; the fourth level is the synergy and long-term effect of cellular and humoral immunity. The immune memory and immune amplification are found in all vertebrates; the fifth level is the appearance of subpopulations of T and B cell functions, such as birds and mammals. The most important event in immune development is the emergence of adaptive immunity. The immune system of evolutionary higher animals consists of both innate and adaptive immunity. Compared with innate immunity, adaptive immunity has more diverse antigen recognition capabilities, more complex regulatory strategies, and significant immune memory and amplification capabilities. Adaptive immunity is primarily mediated by specifically differentiated lymphocytes or lymphoid cells. Current data suggest that the evolution of adaptive immunity occurs in the narrower space-time phase of transition from a jawless vertebrate to a mandibular vertebrate. This development process can be seen in the development of fish. Eight eyes and seven scorpions have a spine and no jaws, belonging to the vertebrate; shark's spine lacks a hard bone structure, which is a special cartilage fish; zebrafish has a spine with a jaw and belongs to the bony fish. By comparing the differences in immune cells and immune molecules in these fishes, the development of the adaptive immune system and two different antigen recognition systems can be seen relatively clearly. Innate immunity is widely present in animals and plants, and pathogens are recognized by a pattern recognition receptor (PRR), and the antibacterial action is exerted by binding of soluble molecules (antibacterial peptides, lysozyme, complement, etc.) or phagocytosis of phagocytic cells. The gene encoding PRR does not recombine during differentiation from germline cells to mature somatic cells, so the polymorphism is not abundant. From the eight-eye and seven-spots with spine and no jaws to the bony fish with spines and jaws to the more advanced birds and mammals, there are special differentiated lymphocytes. These lymphocytes develop highly polymorphic antigen recognition receptors with a broader recognition capacity and significant immunological memory and are therefore considered adaptive immune systems. The diversity of these antigen recognition receptors is achieved by gene rearrangement at the DNA level during somatic differentiation. There are two known antigen recognition patterns: one is the immunoglobulin produced by B cells and the TCR produced by T cells; the other is the variable lymphocyte receptor. The former is found in all vertebrate animals, while the latter is found in octopus and scorpionfish. The shark is evolutionarily between the jawless spine and the bony fish. It is the oldest known to have Ig/TCR/MHC. The basic adaptive immune system of the animal, it is speculated that the formation and divergence of the two adaptive immune patterns occurred in the transient process from the jawless spine to the evolution of the maxillary spine. It is still not clear whether the evolution of these two recognition patterns is contextual or parallel. The diversity of Ig and TCR is achieved through the recombination of immunoglobulin V, D and J segments. TCR is matured with the development of T cells in the thymus. The positive selection and negative selection process determine the TCR profile of T cells entering the periphery. MHC plays a key role in the thymus selection of T cells, and the genetic recombination of Ig and TCR is required. The diversity of VLR is determined by the variable number of LRRs inserted into the VLR locus, and the mechanism of LRR insertion is replication rather than exchange. RAG and MHC are not involved in the VLR recombination process, and no thymus-like tissue has been found in the scorpion. The VLR is available in VLRA and VLRB. Lymphocytes expressing VLRA and VLRB are functionally like T cells and B cells, respectively, and can recognize antigens, producing immune responses and memories. There are some controversial basic questions about the evolution of the immune system. Traditionally, the evolutionary dynamics of adaptive immunity have been thought to be the pathogenic stress caused by changes in microbial species in the living environment, with the goal of synergizing with innate immunity to enhance defense capabilities. However, about 90% of animal species do not have adaptive immunity but are rarely infected by microorganisms. Many microorganisms parasitic in the body are beneficial to the host. Therefore, the development of the immune system is not just to remove all microorganisms more efficiently, but to selectively prevent disease-causing microorganisms while establishing a harmonious symbiotic relationship with beneficial microorganisms. The evolution of the immune system does not seem to be always beneficial. Adaptive immunity often mediates the development of many diseases, such as autoimmune diseases, cancer, and diabetes.

Immune system development related disease and mechanisms

Primary immunodeficiency disease: A loss of protein function due to genetic variation, and a person with impaired immune function is called a primary immunodeficiency disease. Since the first PID was discovered in 1952, more than 90 kinds of PID have been confirmed so far. Most of the genetic forms are autosomal recessive, followed by X-linked inheritance, and only a few are autosomal dominant inheritance. Although the etiology of PID is complex, its clinical manifestations are extremely complex, but their common manifestations are repeated. Mainly for respiratory infections, followed by the digestive tract and skin infections, can also develop into systemic infections such as sepsis. Infectious pathogens vary with PID, and the common feature is the less toxic chance bacteria. Special immunodeficiencies may also have special pathogenic bacteria, such as interleukin 12 (IL-12) and IFN-γ deficiency, prone to mycobacterial infection. The probability of developing a tumor and autoimmune diseases in PID children is tens to 100 times higher than that in normal people. About 80% of PIDs are accompanied by serum immunoglobulin (IG) or antibodies, and serum immunoglobulin levels should be noted when screening in the laboratory. About 18% of PIDs are functional defects of Mf and PMN. Secondary immunodeficiency disease: The immune function is impaired due to environmental factors after birth, resulting in low immune function and repeated infection. The most common SIDs in childhood are nutritional disorders such as vitamin A, trace element zinc, iron-deficiency, and obesity. After correcting the nutritional disorder, the immune function will return to normal. Some primary diseases are often associated with immunodeficiencies, such as infections, tumors, nephrotic syndrome, intestinal malabsorption, and trauma. Neonatal and elderly immune function is also significantly lower is the main cause of infection. How to improve the immune function of this group of people is also one of the current research topics. Inflammatory diseases: In the pathogenesis of toxic shock, especially irreversible shock and multiple organ failure, proinflammatory cytokines IL-1, IL-6 and tumor necrosis factor play an important role. As the immune system is activated, many pro-inflammatory factors are produced to promote the secretion of many more intense inflammatory factors such as endothelin, such as endothelial cells, which promote the expansion of the inflammatory response. Endothelial cells express a variety of adhesion molecules and platelet aggregation. Failure and multiple organ perfusion disorders. These diseases are also known as systemic inflammatory response syndrome. Antagonists of IL-1, IL-6 and tumor necrosis factor have been used in clinical trials. Infectious disease: The process of infection is the process by which a pathogen invades a host to elicit an immune response and destroy the invading pathogen. Therefore, infectious diseases are clinical manifestations of immune responses. In the case of immunodeficiency, it is prone to infection and the infection is particularly serious. For example, the so-called non-reactive or refractory tuberculosis is mostly caused by mutation of theil-12receptor gene. Infection can also cause immunodeficiency. A typical example is the lack of CD+ 4 T cells caused by HIV infection. In fact, all infections can cause temporary immune dysfunction. Vaccines for infectious diseases that seriously endanger children's health are being developed. Allergic diseases: Allergic diseases such as asthma, allergic rhinitis, atopic dermatitis, and contact dermatitis are prone to the decline of Th1 cytokine activity, while Th2 cytokines are hyperactive. How to promote the transformation of Th cells into Th1 cells instead of transforming into Th2 cells is a hot topic in current research. DC1 secretes IL-18, which is an important factor in the induction of Th1 transformation. To prevent the formation of the allergic constitution, how to induce the activity of DC1 is particularly important. Once the Th2 advantage is formed, it is difficult to reverse it to Th1. Most scholars believe that early pregnancy, fetal and neonatal Th2 hyperfunction, the Th1 function is poor, which is a physiological phenomenon to prevent maternal and child rejection. At this stage, exposure to a very small amounts of allergens can promote the continued activation of Th2 leading to allergies. Therefore, work to prevent allergies should start during the perinatal period.


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