1963年 Coombs 和 Gell 根据反应发生的速度、发病机制和临床特征将超敏反应分为I、II、III和IV型。
A number of antigens that can trigger inflammatory allergenic immune responses have been identified, originating from plants (trees, grasses), fungi (Alternaria alternata), arthropods (mites, cockroaches), and other mammals (cats, dogs, cows). They can be species-specific or molecules with broad biochemical homology among many species (eg, tropomyosin).
From an immunological perspective, allergens are linked by their ability to activate the innate immune system at mucosal interfaces, initiating the influx of APCs that subsequently promote Th2-polarized adaptive immune responses (see innate immune responses to allergens). In most cases, an antigen has several epitopes, reacting with different antibodies. Antibodies recognize either a linear sequence of amino acids (linear epitopes) or a three-dimensional motif (conformational epitope).
For one antigen source, a major antigenic determinant is defined as an epitope to which >50% of allergic patients’ sera react, or in other terms, display specific IgE. Cross-reactivity is defined as the ability of an antigen to bind with an antibody that was raised to a different antigen and is observed in the pollen FA syndrome (PR-10 family). It is explained by either linear sequence homology between epitopes from the same biochemical family or by conformational homology, originated from threedimensional conformation making discontinuous amino acids come together.
已经鉴定出许多可以引发炎症性过敏免疫反应的抗原,它们来源于植物(树木、草)、真菌(链格孢)、节肢动物(螨虫、蟑螂)和其他哺乳动物(猫、狗、牛)。它们可以是物种特异性的,也可以是许多物种之间具有广泛生化同源性的分子(如原肌球蛋白)。
从免疫学的角度来看,过敏原是通过它们在粘膜界面激活先天免疫系统的能力联系在一起的,从而引发APC的流入,进而促进Th2极化的适应性免疫反应(见对过敏原的先天免疫反应)。在大多数情况下,抗原有几个表位,与不同的抗体反应。抗体识别线性氨基酸序列(线性表位)或三维基序(构象表位)。
对于一种抗原源,主要抗原决定簇被定义为一种表位,50%以上的过敏患者血清对其反应,或者换句话说,显示特异性IgE。交叉反应性被定义为抗原与产生不同抗原的抗体结合的能力,在花粉FA综合征(PR-10家族)中观察到。它可以通过来自同一生化家族的表位之间的线性序列同源性或构象同源性来解释,构象同源性起源于使不连续氨基酸聚集在一起的三维构象。
人体不断遇到来自环境的多种抗原,包括需要消除的有害病原体以及共生微生物、食物蛋白质或吸入颗粒等无害物质。如前所述,免疫系统能够区分两者并相应地产生适当的反应非常重要。皮肤和粘膜层内的先天免疫细胞处于宿主防御的前线,是第一个暴露于环境过敏原的细胞。我们对先天免疫反应的了解大多来自它对病原体的反应,在那里它们在触发强有力的保护性反应中起着哨兵作用(第4章)。先天免疫)。其中,上皮细胞是具有先天免疫功能的结构细胞。粘膜中的主要先天免疫细胞是APC(如DC)、吞噬细胞(如中性粒细胞和单核细胞)和ILCs。在易感个体中,无害的过敏原可以触发先天免疫系统产生强大的Th2介导反应,主要通过三种机制对身体有害。首先,过敏原可能会破坏上皮屏障,通过其内在的酶活性激活先天免疫系统。一些过敏原表现出半胱氨酸或丝氨酸蛋白酶活性(例如,来自屋尘螨、德国蟑螂、真菌、家猫和豚草花粉的过敏原),洗涤剂和食物中的蛋白水解活性(例如木瓜蛋白酶),胰蛋白酶抑制(例如花生主要过敏原Ara h 2)和氧化酶活性(例如豚草花粉)。99203其次,过敏原及其可溶性成分可能含有PAMP或危险相关分子模式(DAMP),如内毒素、几丁质、β-聚糖和MD-2样脂质结合家族(如Der p 2),它们被粘膜表面细胞上的PRRs(如TLR4)识别。204现在人们认识到,某些环境颗粒向先天免疫细胞提供这些危险信号的能力可能是它们成为过敏原、引发过敏反应的能力的基础。最后,许多过敏原,如花生过敏原Ara h 1和尘螨过敏原Der p 1,也含有碳水化合物部分,可以刺激DC上的C型凝集素受体(CLR),从而增强其摄取以激活Th2免疫反应。99
Following initial activation, a subset of T cells can remain in mucosa and associated lymphoid tissues as memory cells, retaining the ability to respond to specific antigens upon reexposure. Hence, tissue-resident memory T cells have been found within the skin in AD, with a predominance of CD8+ T cells. Mouse models of asthma have suggested that CD4+ lung-resident memory T cells persist long-term, following house dust mite challenge, and can be reactivated upon allergen reexposure. In the gut, following prolonged antigen exposure, resident CD4+ T cells accumulate in lymph nodes and Peyer patches. Resident CD4+ T cells constitute up to 50% of all effector/memory cells.