Generation of Antibody Diversity Oliver Backhaus February 21st, 2018 Allelic exclusion means that only clonally identical BCRs were expressed on the B-cell surface and not two different versions from two different alleles. ‥ When V(D)J rearrangement did not produce a functional BCR, the second allele will be activated and tested. When this will also fail, the B cell will die by apoptosis; this process is called clonal deletion.
Allelic exclusion (Wikipedia) Allelic exclusion is a process by which only one allele of a gene is expressed while the other allele is silenced. This phenomenon is most notable for playing a role in the development of B lymphocytes, where allelic exclusion allows for each mature B lymphocyte to express only one type of immunoglobulin.
The adaptive immune reaction to an intestinal helminth infestation begins with local dendritic cells picking up and displaying helminth antigens. In the case of schistosome住血吸虫 parasites, antigens coming from the eggs are the most potent. （https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/helminth-antigens）
Because they occupy such a key position in the immune responses, there has been considerable interest in how DCs interact with helminth parasites, particularly in the context of understanding how adaptive immune responses in helminth-infected animals become Th2-biased. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2632707/)
The term “excretory/secretory antigens” (ES) refers to the parasite molecules that are released at the interface between the parasite and the cells of the immune system by various mechanisms, such as active secretion and diffusion from parasitic soma. These molecules are originated from adult worms intestinal content as well as female worms uterine content released during egg or larval deposition. （中略）. Dendritic cells are mediators between innate and adaptive immunity, consequently, they play the principal role in the recognition, capture, processing, and presentation of helminth ES to T cells.（https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5893867/）
Upon infection, helminths can cause substantial tissue damage and produce excretory-secretory (ES) products (see Glossary) as they migrate through different organs, including the lungs, intestines, liver, and skin, to complete their life cycles. Collectively, helminth-induced wounding and the production of ES products are known to activate distinct hematopoietic and non-hematopoietic cells resulting in the initiation of type 2 immune responses characterized by the population expansion and activation of innate immune cells including dendritic cells (DCs), basophils, eosinophils, mast cells (MCs), ILC2s, and specialized hematopoietic stem/progenitor cells (HSPCs). （https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168350/）
The induction of Th2 immunity has been shown to be important for resistance to helminth infections in various model systems; however, despite induction of a Th2 response, total clearance of the parasites rarely occurs in man. This implies that helminths have evolved strategies, such as evasion or suppression of the host immune response that prevent their expulsion and permit their long-term survival. (https://onlinelibrary.wiley.com/doi/10.1002/eji.200940109)
How sensitisation to the drug occurs, to what extent T cells are involved, and how the different pathologies are related to the symptoms of drug allergy are still unknown. https://thorax.bmj.com/content/55/suppl_2/S61
アレルギーと２型免疫応答
allergic diseases are characterised by a skewing of the immune system towards a T-helper cell type-2 (Th2) phenotype https://erj.ersjournals.com/content/26/6/1119
The majority of patients with AD, CRS and asthma involve, or result from, an overexpression of type 2 inflammatory pathways https://onlinelibrary.wiley.com/doi/10.1111/all.14318
Effect of neuromedin U on allergic airway inflammation in an asthma model (Review) December 4, 2019
In allergic eosinophilic airway inflammation, specialized dendritic cells present allergens
to steer the differentiation of naive T lymphocytes
towards the formation of Th2 cells,
which produce cytokines such as interleukin-4 (IL-4), IL-5, IL-9 and IL-13
that result in IgE switching in B cells.
The released IgE molecules bind to the Fc epsilon receptor I (FcεRI) on mast cell surfaces.
Exposure to allergens
and the cross-linking of receptors by allergens, which bind to high-affinity IgE
result in mast cell degranulation.
Type 2 innate lymphoid cells (ILC2s) are activated by cysteinyl leukotrienes (CysLTs) and prostaglandin D2 (PGD2) secreted by activated mast cells.
Once activated, ILC2s rapidly expand and secrete large amounts of IL-5 and IL-13.
ILC2s contribute to allergic airway inflammation by directly interacting with Th2 cells to promote the release of cytokines, mucus production and airway eosinophilia.
Antigen-presenting cells introduce processed allergens to T-helper lymphocytes, where a decision of developing different types of T-cell immunity is given under the influence of several cytokines, chemokines, costimulatory signals and regulatory T cells.
Among Th2-type cytokines, interleukin (IL)-4 and IL-13
are responsible for class switching in B cells,
which results in production of allergen-specific IgE antibodies
that bind to specific receptors on mast cells and basophils.
After re-exposure to the sensitized allergen, this phase is
followed by activation of IgE Fc receptors on mast cells and basophils
resulting in biogenic mediator releases responsible for the symptoms and signs of anaphylaxis.
IgE is produced by B lymphocytes and plasma cells, but in order to become an IgE‐producing plasma cell the naive B cell needs a number of molecular signals, most importantly provided by a Thelper lymphocyte with a specialized cytokine secretion profile—the so‐called Th2 type (Th2) which can produce the cytokines necessary for stimulation of the B cell to IgE class switch (interleukin (IL‐) 4, IL‐13), for stimulation and recruitment of eosinophils (IL‐5, IL‐9, granulocyte/macrophage‐colony stimulating factor (GM‐CSF) and for other inflammatory tissue reactions (IL‐9, IL‐13).
Undifferentiated Th cells on the other hand also need signals to develop into the Th2 phenotype, and it is likely that specialized dendritic cells are responsible for this process.
次に、起こる順でも、再度まとめています。
Thus three steps are crucial to mount an IgE immune response:
1) differentiation of dendritic cells to ‘DC2’ promoting
2) the formation of allergen‐specific Th2 cells which subsequently
3) induce the differentiation of B lymphocytes to IgE isotype switch and transformation to an IgE‐producing plasma cell. The molecular background of these processes is discussed in more detail in the second part of this paper.
Th2 cells are mainly involved in host defense against large extracellular pathogens, such as helminths.
Naïve CD4 T cells after receiving signals from DCs
may differentiate into Th2 cells after their activation.
IL-2 and IL-4 are two important cytokines during Th2 cell differentiation, particularly in vitro.
IL-2 and IL-4 activate STAT5 and STAT6, respectively,
and the latter induce the expression of the Th2 master transcription factor GATA3 in activated CD4 T cells.
Differentiated Th2 cells secret lineage cytokines including IL-4, IL-5, and IL-13.
During a classic type 2 immune response, IL-4 promotes B cell antibody class switching to immunoglobin E (IgE),
IL-5 recruits eosinophilia to the inflammation sites,
and IL-13 promotes mucus production and goblet cell hyperplasia.
Th2 cells and ILC2s also express chemokine receptors on the cell surface, including CCR3, CCR4, and CCR8, to receive migration signals from ligands (CCL11 for CCR3, CCL17 and CCL22 for CCR4, and CCL1 for CCR8) secreted by epithelial cells.
In addition to recruiting Th2 cells and ILC2s, these chemokines can also recruit other cells, such as DCs, eosinophils, basophils, and mast cells to the damaged epithelial sites caused by helminth infection or protease allergens.
専門医のためのアレルギー学講座 34．免疫学における基礎と新たな展開 3．アレルギー発症と制御における B 細胞の役割 アレルギー 68（6）， 661―667， 2019（令1）アレルギー反応は I～IV 型に 分類されるが，IgE 依存的な即時型アレルギー反応が I 型アレルギーである．IgE を介した免疫反応は寄生虫 に対する感染防御において重要である一方，様々なア レルギー疾患に関与している．
Multi-faceted regulation of IgE production and humoral memory formation Allergology International Volume 70, Issue 2, April 2021, Pages 163-168 IgE antibody (Ab) is produced by plasma cells (PCs) derived from B cells having undergone class-switching (CS) to IgE isotype during type 2 immune responses. IgE plays a pivotal role in protection against parasite infection and environmental toxins by activating mast cells and basophils through binding FcεRI, a high-affinity Fc receptor for IgE. On the other hand, IgE is best known as a mediator of allergic responses through the same mechanism. IgE産生に関する詳細なレビュー論文
Biology and dynamics of B cells in the context of IgE-mediated food allergy 03 December 2020 B cells play a pivotal role in IgE-mediated food allergies, as a result of their unique ability to produce allergen-specific IgE antibodies that sensitize mast cells and basophils by binding to their high-affinity IgE receptors (FcεRI). Subsequent allergen cross-linking of FcεRI-bound IgE on mast cells and basophils initiates the release of pro-inflammatory mediators resulting in a type I hypersensitivity reaction.
ラポール維持管理のストラテジー : 交渉場面における「格下げ表現」 神田 靖子, Yasuko Kanda 同志社大学留学生別科441-58 Helen S. Oatey(2000)の提唱する「ラポール維持管理のストラテジー」は,ラポール(親愛感情)を維持することがポライトネスであるとして,5つの「ポライトネスの領域」によってラポール維持管理がなされるという。
死の甘いキス：ガレクチン‐１，糖鎖修飾，免疫特権生成をつなぐもの Rubinstein Natalia, Toscano Marta A., Ilarregui Juan M., Bianco Germán A., Rabinovich Gabriel A., 佐々木 洋子 FCCA(Forum: Carbohydrates Coming of Age)1796133-143
