Departments of Experimental Immunology and Otorhinolaryngology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Room K0-130, 1105 AZ, Amsterdam, The Netherlands.
Clin Transl Allergy. 2014 Apr 15;4(1):12. doi: 10.1186/2045-7022-4-12.
Allergic sensitization is the outcome of a complex interplay between the allergen and the host in a given environmental context. The first barrier encountered by an allergen on its way to sensitization is the mucosal epithelial layer. Allergic inflammatory diseases are accompanied by increased permeability of the epithelium, which is more susceptible to environmental triggers. Allergens and co-factors from the environment interact with innate immune receptors, such as Toll-like and protease-activated receptors on epithelial cells, stimulating them to produce cytokines that drive T-helper 2-like adaptive immunity in allergy-prone individuals. In this milieu, the next cells interacting with allergens are the dendritic cells lying just underneath the epithelium: plasmacytoid DCs, two types of conventional DCs (CD11b + and CD11b-), and monocyte-derived DCs. It is now becoming clear that CD11b+, cDCs, and moDCs are the inflammatory DCs that instruct naïve T cells to become Th2 cells. The simple paradigm of non-overlapping stable Th1 and Th2 subsets of T-helper cells is now rapidly being replaced by that of a more complex spectrum of different Th cells that together drive or control different aspects of allergic inflammation and display more plasticity in their cytokine profiles. At present, these include Th9, Th17, Th22, and Treg, in addition to Th1 and Th2. The spectrum of co-stimulatory signals coming from DCs determines which subset-characteristics will dominate. When IL-4 and/or IL-13 play a dominant role, B cells switch to IgE-production, a process that is more effective at young age. IgE-producing plasma cells have been shown to be long-lived, hiding in the bone-marrow or inflammatory tissues where they cannot easily be targeted by therapeutic intervention. Allergic sensitization is a complex interplay between the allergen in its environmental context and the tendency of the host's innate and adaptive immune cells to be skewed towards allergic inflammation. These data and findings were presented at a 2012 international symposium in Prague organized by the Protein Allergenicity Technical Committee of the International Life Sciences Institute's Health and Environmental Sciences Institute.
过敏致敏是过敏原在特定环境背景下与宿主相互作用的复杂结果。过敏原在致敏过程中遇到的第一道屏障是黏膜上皮层。过敏性炎症性疾病伴随着上皮通透性的增加，使上皮更容易受到环境触发因素的影响。过敏原和环境中的共同因素与先天免疫受体相互作用，如上皮细胞上的 Toll 样受体和蛋白酶激活受体，刺激它们产生细胞因子，在过敏倾向个体中驱动 T 辅助 2 样适应性免疫。在这种环境中，与过敏原相互作用的下一组细胞是位于上皮层下方的树突状细胞：浆细胞样树突状细胞、两种类型的常规树突状细胞（CD11b+和 CD11b-）和单核细胞衍生的树突状细胞。现在越来越清楚的是，CD11b+、cDCs 和 moDCs 是指导幼稚 T 细胞成为 Th2 细胞的炎症性树突状细胞。T 辅助细胞中非重叠稳定的 Th1 和 Th2 亚群的简单范例正在迅速被更复杂的不同 Th 细胞谱所取代，这些 Th 细胞共同驱动或控制过敏炎症的不同方面，并在其细胞因子谱中表现出更大的可塑性。目前，除了 Th1 和 Th2 之外，还包括 Th9、Th17、Th22 和 Treg。来自 DC 的共刺激信号谱决定了哪些亚群特征将占主导地位。当 IL-4 和/或 IL-13 发挥主导作用时，B 细胞会转向 IgE 产生，这一过程在年轻时更为有效。已证明产生 IgE 的浆细胞寿命长，隐藏在骨髓或炎症组织中，难以通过治疗干预靶向。过敏致敏是过敏原在其环境背景下与宿主固有和适应性免疫细胞向过敏炎症倾斜的趋势之间的复杂相互作用。这些数据和发现是在 2012 年布拉格由国际生命科学研究所健康与环境科学研究所的蛋白质变应原性技术委员会组织的国际研讨会上提出的。
