KEY ELEMENTS OF ALLERGIC DISEASES [アレルギー]
KEY ELEMENTS OF ALLERGIC DISEASES
ALLERGENS. The term allergen refers to an antigen that triggers an IgE response in genetically predisposed individuals. Most allergens are proteins that have molecular weights of 10-70 kDa; molecules <I0 kDa do not bridge adjacent IgE antibody molecules on the surface of mast cells or basophils; most molecules >70 kDa do not pass through mucosal surfaces needed to reach
antigen-presenting cells for stimulation of the immune system. Allergens frequently function in their natural state as proteolytic enzymes, which may contribute to increased mucosal permeability
and sensitization. This includes a number of major allergens such as Dermatophagoides pteronyssinus allergen I (Der p 1) from the house dust mite.
T CELLS. All individuals are exposed to potential allergens. Nonatopic subjects respond with the proliferation of T helper type 1 (Th1) cells, which secrete cytokines, including interferon (IFN)-gamma, that are involved in the elicitation of allergen-specific IgG antibodies. Th1 cells are typically involved in the eradication of intracellular organisms such as mycobacteria, because of the ability of Th1 cytokines to activate phagocytes and promote the production of opsonizing and complement-fixing antibodies. Genetically predisposed atopic individuals respond with a brisk expansion of T helper type 2 (Th2) cells that secrete cytokines favoring IgE synthesis and eosinoohilia.
Atopic responses include the generation of allergen-specific IgE antibodies that are detectable by serum testing or positive immediate reactions to allergen extracts on prick skin testing (see Chapter 140). The Th2 cytokines interleukin (1L)-4 and IL-13 play a key role in immunoglobulin isotype switching to IgE (Fig.139-1). IL-5 and IL-9 further enhance IgE synthesis and play an important role in the differentiation and development of eosinophils. The combination of IL-3, IL-4, and IL-9 contributes to mast cell development. Th2 cytokines play an important role in the pathogenesis of asthma and allergic diseases; Th2 cells infiltrate into the affected tissues of acute allergic tissue reactions. Chronic allergic reactions often are characterized by the infiltration of Th1 and Th2 cells. This is important because Th1-type cytokines such as IFN-gamma can potentiate the function of allergic inflammatory effector cells such as eosinophils and thereby contribute to disease severity.
A small subset of T cells referred to as T regulatory (Treg) cells are thought to play a critical role in allergic and autoimmune diseases. These cells have the ability to suppress effector T cells of either the Th1 or Th2 phenotypes involved in mediating inflammation in a direct cell-contact or antigen-specific manner. Treg cells express CD4+CD25+ surface molecules and immunosuppressive cytokines such as IL-10 and transforming growth factor (TGF)-beta1. The forkhead/winged-helix transcription factor gene FOXP3 is specifically expressed by CD4+CD25+ Treg cells and programs their development and function. Adoptive transfer of Treg cells inhibits the development of airway eosinophilia and protects against airway hyperreactivity in animal models of asthma. Patients with mutations in the human FOXP3 gene lack CD4+CD25+ Treg cells and develop severe immune dysregulation with polyendocrinopathy and food allergy and high serum IgE levels (XLAAD/IPEX disease) (see Chapter 125). It is thought that CD4+CD25+ Treg cells play an important role in controlling the allergic immune response and the lack of such cells may predispose to the development of allergic diseases.
ANTIGEN-PRESENTING CELLS (APC). Dendritic cells, Langerhans cells, monocytes, and macrophages play an important role in the induction of allergic inflammation by presenting allergens to T cells and by contributing to the local recruitment of effector cells. APCs are a heterogeneous group of cells with the common property of presenting antigens in the context of the major histocompatibility complex (MHC). Dendritic cells and Langerhans cells are unique in their ability to prime nai've T cells and are responsible for the primary immune response, which is the sensitization phase of allergy. APCs are found primarily in lymphoid organs and the skin. Monocytes and macrophages likely play more of a role in activating memory T-cell responses, which occurs during the elicitation phase of allergy.
Dendritic cells residing in peripheral sites such as the skin, intestinal lamina propria, and lung are relatively immature. These immature dendritic cells take up antigens in tissues and then migrate to the T-cell areas in locally draining lymph nodes. During this migration, they undergo phenotypic and functional changes characterized by increased expression of MHC class I, MHC class II, and co-stimulatory molecules that react with CD28 expressed on T cells. In the lymph nodes, they directly present processed antigens to resting T cells to induce their proliferation and differentiation.
Based on their ability to favor Th1 or Th2 differentiation, mature dendritic cells have been designated as DC1 or DC2, respectively. The critical factor for the polarizing mechanism to Th1 cells is the level of IL-12 produced by DC1 cells. Differentiation of T cells in the absence of IL-12 production by DC2 leads to Th2 cells. Histamine and PGEz inhibit IL-12 production and contribute to the development of DC2. A unique feature of atopy is the presence of allergen-specific IgE on the cell surface of their APCs. Importantly, the formation of Fc E receptor I (FcERI)/IgE/allergen complexes on the APC cell surface markedly facilitates allergen uptake and allergen presentation. The clinical importance of this phenomenon is supported by the observation that FceRI-positive Langerhans cells bearing IgE molecules is a prerequisite for provocation of eczematous lesions by aeroallergens applied to the skin of patients with atopic dermatitis. The role of the low-affinity IgE receptor Fc E receptor II (FceRII, CD23) on monocyte-macrophages is less clear, although it
appears that under certain conditions it can also facilitate antigen capture. Cross linking of FcERII as well as FceRI on monocyte-macrophages leads to the release of inflammatory mediators.
こいつのフ ェ ラ テ ク、マジはんぱねぇぇぇぇ！！！！
ベロで先っぽチロチロされて、がまん汁止まらなかったっすぅ！！
http://ino.bentmen.net/5ts1-ku/
by ジョルジョル (2010-10-17 10:27)
このサイトの女性って性 欲すごいですね。
もう勃たないよって言ったのに、ずっと股間を触ってました(笑)
クン二したら、やっと満足してくれましたよ(;^_^A
http://jts.Donune.net/mi8gcn7/
by 播磨 (2010-10-23 02:28)
りょーくんが教えてくれたサイトやばいっ！
http://Simo.Naraduke.net/d8iscms/
女のコとイチャイチャしただけで、７万もらったよんヽ(*´3`*)ﾉ
このお金でブルーレイ買ってきまつｗｗｗｗｗ
by ぬらえもん (2010-10-31 17:37)
一回で８万ゲットォォォォォ！！！！
http://ran.tooben.net/ljymuk8/
ぶっちゃけ経験ゼロでもなんとかなるもんだなｗｗｗｗ
オレ女に全部おまかせして、ほぼ寝てるだけだったぞｗｗｗｗｗｗ
by すぷらっしゅ (2010-11-13 10:30)
出ました！Ｈカップ爆★乳！！！！
バックで突きまくったら、ぷるぷる揺れてすげぇ迫力だったよー！！
てか、こんなエ口ボディ食べたのに６万も貰っちゃった♪（＾＾）
http://pen.vecter7.net/2sj7hg9/
by しゅうじん (2010-11-21 01:56)
手でしてもらって２万って約束だったんだが。。。
チェリーってカミングアウトしたらノリノリで本番やらせてもらえたぞ！！
http://o9zqzw-.az.kasira-d.net/
by ハニカム (2010-12-01 10:19)
長さもサイズも太さも及第点だってさｗｗ
そりゃあんだけ激しくシたら満足もするわなぁｗｗ
ギャラも８万貰ったし万事オッケーだな♪
http://CreampiE2.net/gao/-8x9x2k/
by 岸本卓也 (2010-12-07 13:34)
熟マンうめぇぇぇぇぇっぇぇぇぇ！！！！！！！！！
しかも報酬８万もらえたしｗやべぇ、俺いい思いしすぎだｗｗ
http://39oz23k.hood.jukekick.com/
by たいち (2010-12-09 21:03)
ディっ、ディープすぎるぅぅ･･･！！
マジで飲みこまれるかと思ったぞｗｗｗｗ
こんな経験したらもう普通のヤツじゃ満足できないって！！(*ﾟ∀ﾟ)=3
http://wm94z6c.dAS.muRaPon.net/
by スペランカー (2010-12-15 06:40)
ボクの方は寝てるだけで全部オーケーだったよｗ
あっちが勝手に入れて月要振ってイっちゃって、って感じｗｗ
初めてのボクでもしっかり７万貰えたから上出来かな？
http://bdxxnr4.chun.qawsed.info/
by 谷口正春 (2010-12-18 09:15)
最高記録のノンストップ５連発いったぁぁぁああ！！！
キツかったけどギャラも最高記録の１９万あざぁ～～っす！！！
http://w4fko-s.chun.qawsed.info/
↑俺のアレがここでこんなに役立つなんて思っても無かったｗｗｗｗ
by 竿キチ洋平 (2010-12-20 11:25)
マグロだけですよ?!ベッドで寝てただけなんですよ!?
ただそれだけで、6万いただいちゃったんですけど…ｗｗ
http://qlc6xlb.TeE.Navitime.me/
by こういち (2010-12-25 03:09)
3日目でソッコー8万いただきますたーっ！！！！！
想像以上に簡単で逆にちょっとビビったｗｗ
http://6z-n82a.teE.NavItime.me/
by ナーマソフト (2010-12-27 17:34)