Allergy and Hypersensitivity. Chapter 14

Transcription

1 Allergy and Hypersensitivity Chapter 14

2 Four types of hypersensitivity reactions (by Coombs and Gell) B B B T Th2 Atopic dermatitis granulomas

3 過敏反應之類型 過敏反應型式 抗體或參與作用的細胞 範 例 B 第 Ⅰ 型立即性過敏 肥胖細胞或嗜鹼性球上的 IgE 抗體 藥物注射或昆蟲毒素引起之全身性休克反應 ; 一般之過敏如乾草熱 氣喘 B 第 Ⅱ 型細胞毒殺性過敏 IgM IgG 及補體 輸血反應,Rh 不相容性 ; 肺出血腎綜合症候群 ; 自體免疫溶血性貧血 B 第 Ⅲ 型免疫複合物過敏 IgM IgG IgA 及補體 全身性紅斑狼瘡, 類風濕性關節炎 T 第 Ⅳ 型細胞媒介性過敏 T 細胞 淋巴激素及單核球激素 移植組織之排斥 ; 愛迪生症 ; 接觸性皮膚炎 ; 肺結核 ; 肉狀瘤病 ; 多肌炎

4 IgE-mediated reactions to extrinsic Ags (penicillin) (anaphylactic shock) (atopic dermatitis)

5 Skin test +, as wheal-and-flare reaction

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7 Properties of inhaled allergens Kd Identification: 1. reactive IgE 2. skin test 3. IgE in animals

8 The enzymatic activity of some allergens enables the penetration of epithelial barriers occludin Der p 1, a cysteine protease Also papain (Cys protease) - used as meat tenderizer - cause occupational allergy

9 Sensitization involves class switching to IgE production on the contact with an allergen How does APC (or DC) induce the differentiation of Th2 cells? Might through the interaction of CCL2 (MCP-1), CCL7 (MCP-3), and CCL13 (MCP-4) via CCR2 on activated monocytes: reduced IL-12 production.

10 Ag binding to IgE on mast cells leads to amplification of IgE production

11 IgE level and atopic diseases (extrinsic) 外因性 (intrinsic) 內因性 異位性

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13 Genes, the environment, and atopic allergic diseases Halle (with pollution) vs. Munich less prevalence of asthma high IgE and EO

14 Susceptibility loci identified by genome screens for asthma, atopic dermatitis, and other immune disorders

15 5q31.1 sid-pair analysis IgE 1. IL-4, IL-5, IL-9, IL-13, and GM-CSF cluster 2. TIM family (for T cell, immunoglobulin domain and mucin domain), Tim-1, a HAV R 3. p40 of IL-12 Science :1152

16 Candidate susceptibility genes for asthma 1. IgE production 2. Inflammatory response 3. Clinical response (6p) (5q31-33) (11q12-13) a metalloproteinase, for airway remodeling (20p13) Affect the response to bronchodilator therapy with 2-adrenergic agonist.

17 Epidemiological observations about asthma and allergy 1. Allergic disease is more common in clean westernized environments? 2. Asthma and atopy are less common in younger siblings? 3. Asthma and atopy are less common in households with dogs as pets? Environmental factors: 1. Infectious diseases in early childhood 2. Environmental pollution 3. Allergen levels 4. Dietary changes life styles

18 Hygiene hypothesis Asthma: an epidemic of dysregulated immunity counter-regulation hypothesis: IL-10 and TGF- production upon childhood infection, and inhibit both Th1 and Th2 responses (page 580) IDO (indoleamine 2,3-dioxygenase) and Treg cells (page 581) Nat Immunol 3:715, 2002

19 Mast-cell activation has different effects on different tissues The effector function!

20 Mast cells and basophils B cells, activated T cells, monocytes, eosinophils, platelets, FDCs page 583

21 Molecules released by mast cells on activation

22 Eosinophil chemotaxis: Eotaxin 1 (CCL11) Eotaxin 2 (CCL24) Eotaxin 3 (CCL26) Receptor: CCR3 Eosin stain: page 587

23 EOs secrete toxic granule proteins and other inflammatory mediators (ECP)

24 Allergic reactions can be divided into an immediate response and a late-phase response

25 The acute response in allergic asthma leads to Th2- mediated chronic inflammation of the airways Airway remodeling: a thickening of airway walls due to hyperplasia and hypertrophy of the smooth muscle layer and mucous glands, with the eventual development of fibrosis. page 589

26 Morphological evidence of chronic inflammation in the airways of an asthmatic patient Occlusion of the airway by a mucous plug. Cell infiltrate

27 Food intolerances vs. food allergy

28 Approaches to the treatment of allergy - in use ( 欣流, Singulair- Montelukast) by 張子文教授

29 Bronchial dilators 15-4

30 Hyposensitization Desensitization or specific allergen immunotherapy (page 596) - 稱減敏療法

31 Approaches to the treatment of allergy - proposed

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33 Damages resulted from ADCC (antibodydependent cell-mediated cytotoxicity) 1. Oxygen radicals 2. Chemo-attractants 3. Complements: C5-C9

34 HDNB (haemolytic disease of the newborn) (Ab Rh factor)

35 The deposition of immune complexes in tissues causes a local inflammatory response known as an Arthus reaction (Type III) also known as farmer s lung (inhale high level antigens)

36 Serum sickness is a classic example of a transient immune complex-mediated syndrome 7

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38 Anti-IgG

39 Type IV hypersensitivity responses

40 The DTH response is directed by chemokines and cytokines released by Th1 cells stimulated by Ag

41 The stages of a delayed-type hypersensitivity reaction

42 Elicitation of a DTH response to a contact-sensitizing agent (pentadecacatechol) (IL-8) (IP-9) (MIG, monokine induced by IFN- ) CXCL10 (IP-10) Two phases in cutaneous hypersensitivity response: sensitization and elicitation

43 Physical contact with poison ivy transfers pentadecacatechol, which cause dermatitis

44 The formation of granuloma

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46 Molecular basis of immune recognition of gluten in celiac disease (HLA-DQ2) (modified - gliadin peptide) Gln Gla associate with HLA-DQ2 (95% Pt s) 腹腔性疾病 (Celiac disease) 與麩質敏感性疾病 (Gluten sensitivity disease)

47 A hypothesis to explain antibody production against ttg in the absence of T cells specific for ttg in celiac patients (specific to gluten) (tissue transglutaminase ) 似 autoimmune disease

48 The activation of cytotoxic T cells by the innate immune system in celiac disease by IL-15