Contents What is allergy History of allergy Type

Contents ¥ What is allergy? ¥ History of allergy ¥ Type I hypersensitivity reaction ¥ Effector cells in allergy 2

What is allergy? 3

Early-life origins of allergy and asthma Diet Intra-uterine Postnatal Smoking Maternal environment Lung Immunological morphogenesis development External environment Lung morphogenesis Immunological development (Th 1, Th 2) Atopy Virus-related wheeze External environment Asthma External environment Persistent asthma 4

Earliest recorded case of allergic reaction? ¥ First description of a possible allergic reaction: ¥ The death of the Egyptian King Menes in 2641 BC due to a sting by a wasp Cohen SG Allergy Proc 1989; 10: 149 5

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Type I hypersensitivity reaction 10

Classification of Hypersensitivity 11

Type I Hypersensitivity Reaction 12

Spectrum of Allergic Diseases Rhinitis Anaphylaxis Asthma Conjunctivitis ALLERGY Gastroenteritis Atopic Dermatitis Urticaria 13

Processes in allergy Re-exposure Th 2 bias Genetic susceptibility Sensitization Specific Ig. E Mast cells / basophils Allergen exposure Inflammatory cascade 14

Processes in allergy Sensitization Allergen Specific Ig. E Interleukins B cell Plasma cell Mast cell Mature Th 2 cell Re-exposure Activated mast cell Symptoms Inflammatory mediators and cytokines 15

Allergen Ig. E APC CD 23 B 7 -2 MHC-II IFN-g IL-12 IL-18 CD 28 TCR - Th 2 cell IL-4, IL-13, IL-5 16

Atopic state IL - 4 IL - 13 Ig. E B cell Fce. R 1 Th-2 IL-4 IL-5 MC Bas. Mediators (LTs, PAF, H, etc) TNF-a IL-4, IL-13, IL-3, GM-CSF, IL-16 Chemokines (Eotaxin; Rantes; etc) Acute phases of inflammation Microvascular changes Overexpression of particular adhesion molecules Recruitment of inflammatory cells (ie, eosinophils) Multidirectional cellular and molecular interactions Airway Chronic Inflammation 17

Common Allergens a/w Type I Hypersensitivity Food proteins Insect stings House dust mite proteins Plant pollens Fungal proteins Animal dander 18

Antibodies in allergy ¥ In 1919, a case of asthma caused by allergy to horse dander was shown to be passively transferred by blood transfusion ¥ In 1921, Prausnitz & Kutner demonstrated passive sensitisation of human skin by serum from allergic individuals ¥ In 1968, the new immunoglobulin was designated Ig. E based on the independent work of the Ishizakas in the USA and Bennich & Johansson in Sweden 19

Regulation of Ig. E isotype switching B-lymphocyte Th 1 IFN-g IL-12 negative B cell Th 2 Ig. E IL-4 IL-13 positive 21

Chemical Mediators: mast cell / basophil 22

Chemical Mediators: mast cell / basophil 23

Principal Mediators in Type I HS 24

Effector cells (효과세포) in allergy 25

Effector cell - Mast cell Resting mast cell Degranulated mast cell 27

The mast cell in allergic disease Endothelial activation: adhesion molecule expression Swelling Edema Histamine Mast cell Secretion Irritation Sneezing TNF-a Prostaglandins IL-4 IL-13 Leukotrienes IL-5 IL-6 IL-10 Acute allergic symptoms Th 2 -lymphocyte stimulation Ig. E synthesis Eosinophil/ basophil priming Inflammation Hyperreactivity Chronic symptoms 30

Eosinophil(호산구) 31

호산구-2 ¥ 호산구의 독성 과립 단백질 major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil neurotoxin (EDN), eosinophil peroxidase (EPO) ¤ 숙주 조직에 강력한 독성 효과 ¤ ¥ 활성화된 호산구 IL-1, IL-3, IL-4, IL-5, IL-13, GM-CSF, transforming growth factor(TGF)-α/β, TNF-α, RANTES (regulated on activation, normal T cells expressed and secreted), macrophage inflammmatory protein (MIP)1α, eotaxin 등의 사이토카인들을 분비 ¤ 다양한 면역 반응을 지속시키거나 증폭 ¤ 염증반응과 조직 회복 과정에 관여 ¤ 33

CD 4(+) T cell ¥ Th 1 : IL-2, TNF-β(lymphotoxin), IFN-γ, IL-12를 분비하 여 지연형(delayed type) 과민 반응에 참여 ¥ Th 2 : IL-4, IL-5, IL-9, IL-10, IL-13 등을 분비하여 Ig. E 생 성을 촉진하고 호산구를 활성화시켜 알레르기 염증에 관여 ¤ 비만세포의 활성에 중요한 IL-3와 granulocyte-macrophage colony-stimulating factor(GM-CSF)는 이 두 가지 아형 모두에 서 생산 ¥ Th 17→ neutrophil 반응과 염증반응을 자극 ¥ Treg → T cell 반응과 다른 면역반응을 억제 Two types of Treg ¤ natural regulatory T cells ¤ inducible (adaptive) regulatory T cells 37

The central role of the T cell Antigen-specific T cell Tolerance Mast cell development IL-3, IL-4 IL-9, IL-13 Overproduction IL-4, IL-9 of mucus IL-13 T cell IL-9, IL-11 IL-13 Airway hyperresponsiveness IL-4 IL-13 Ig. E production IL-3, IL-4 IL-5, IL-9 IL-13, GM-CSF Eosinophil and basophil accumulation 41

항원-제시 세포 (antigen-presenting cell: APC) ¥ 기능 : take up antigen, process and present antigen to T cells ¥ 종류: macrophage, dendritic cell, B cell, activated T lymphocyte ¥ Major histocompatibility complex (MHC) Class I: binds with CD 8+ T cell only ¤ Class II: binds with CD 4+ T cell only ¤

Mechanism of Allergic Inflammation 44