Atopy and Allergic diseases .

1. Atopy and Allergic diseases . Prof. Mohamed Osman Gad El Rab. College of Medicine & KKUH.

2. Terminology التعريف : Human disease caused by immune responses to environmental antigens that lead to : immediate reactions in the target tissues & rapid onset of symptoms are called : allergic diseases .

3. With reference to Coombs & Gell classification of hypersensitivity these are : Immediate ( type I )hypersensitivity reactions . In clinical practice these reactions are commonly called : allergy or atopy .

4. atopy : is derived from a Greek term (atopos )which mean : out of place . The term refer to : a strong genetic predisposition استعداد - اهبهfor development of immediate hypersensitivity reactions in certain individuals.

5. The genetics of allergy are complex , involving interactions between several genes . studies of atopic families have identified regions on chromosomes 11q and 5q هذه الكروموسومات المسببه لفرط الحساسيه. وظيفه كل كروموسوم وعلاقته بتكوين فرط الحساسيه: chromosome 11q : encodes the b subunit of the high affinity IgE receptor. chromosome 5q : contain many cytokine genes that increase susceptibility حساسيه .

6. The high- affinity IgE receptor encoded by chromosome 11q . في الاشخاص غير الحساسين يوجد ( اي جي اي ) ولكنه ليس عالي الجاذبيه وكثير العدد مثل الاشخاص الحساسين مسبب الحساسيه يرتبط ب 2 ( اي جي اي )

7. تذكير ( من البلوك الاول ) – الانترلوكين \ هو ماده كميائيه تنتج من الخلايا البيضاء وتؤثر على عده اهداف هذه الاهداف هي خلايا لها علاقه بالجهاز المناعي وتؤثر عليها اما بنتشيطها للانقسام او تنشيطها للتحول للشكل النشط او تحويلها لشكل اخر وهي ترتبط-بريسيبتور خاص على جسم الخليه الهدف .وبذلك يكون لها علاقه باثاره الجهاز المناعي اذا كثرت The 5q locus موقع contain genes for : - IL-3 ,4, 5 , 9 & 13 . -These cytokines : - promote تعزز TH2 تي هلبر سيلز responses by enhancing تنميه : * IgE isotype switching in B cells. * eosinophils survival . * mast cell proliferation . - variation in the IL-4 gene has been associated with high levels of IgE in atopic individuals.

8. Allergy is a systemic disorderشغل العرض Respiratory system Allergic rhinitis Asthma Nose Pharynx Lungs Esophagus GIT skin Stomach Food allergy Skin Eczema Urticaria Allergic dermatitis

9. Clinical presentation الاعراض: atopic individuals may present with one or more of the following conditions : - allergic rhinitis. - allergic conjunctivitis التهاب العين وهو دائما بسبب مناعي . - allergic asthma. - atopic dermatitis ( eczema ).

10. A newborn approximate risk of developing symptoms according to family history of allergic disease : 1. no family member allergic 5-15 %. 2. one sibling allergic 25-35 %. 3. one parent allergic 20-40 %. 4. both parents allergic 40-60 %. 5. both parents allergic , ( same symptom ) 50- 70 %.

11. Epidemiology الوبائيات : The prevalence الانتشار of allergic disease worldwide ranges from 30% to 40%. There is substantial قطعي evidence برهان that the incidence حدوث of allergy is steadily ببانتظام increasing all over the world . A study in U.K. between 2001-2005 showed that the incidence of patients with at least one allergic disease increased from 18.9% to 24.2 %. J R Soc Med. 2008, 101(11):558-563.

12. A study in Saudi Arabia documented a significant increase in incidence : Allergic asthma: From 8% (in 1986 ) to 23% (in 1995). ( p <.0001 ). Allergic rhinitis: From 20% (in 1986 ) to 25% ( in 1995). (p < .003). A.R.Al-Frayh,Z.S hakoor,M.O.GadElRab.Annal of Allergy, Asthma &Immunology, 2001,86:292-296.

13. * Allergic disease is the 5 th leading chronic disease among all ages . * And the 3rd chronic disease among children under 18 years old ; up to one child in three is affected . * Trend الميل يشير الى انه indicate that by 2015 half of all Europeans may be suffering from an allergy مساكييين ( مسوي طالع منها ) .

14. Antigens that elicit تثير allergic reactions are called allergens because they have the following features : 1. low molecular weight. 2. glycosylationمن القاموس : the formation of linkages with glycosyl groups. 3. high solubility in body fluids . 4. proteins, in nature ,or chemicals bound to proteins , and some have enzyme activity .

15. Common allergens associated with type 1 hypersensitivity : حبوب اللقاح للفطريات

16. Fungal spores (aspergillus ) common indoor & outdoor allergens بالبيت وخارج البيت ( ورانا ورانا ).

17. tree pollens ( mesquite ) common outdoor allergens in Saudi Arabia ..

18. Ragweed & ragweed pollens : common outdoor allergen .

19. House dust mite & Cockroach صرصورinsects : Common indoor allergens that may cause allergy symptoms All through the year . ( perennial ) .

20. Honey-bee black( fire ) ant .Common causes of anaphylaxis ظهور شديد وفوريللحساسيه ( تفصل لاحقا ) ..

21. Manifestations ظهور of allergic disease require two steps . 1. sensitization phase : الاصابه الاولى first exposure to allergen. 2. challenge phase : الاصابه اللاحقه re-exposure to allergen .

22. Sequence of events in immediate H/S reactions. First exposure to allergen. Activation of TH2 cells & stimulation of IgE class switching in B –cells . Binding of IgE to FcR1 on mast cells. sensitization .

23. Sequence of events in immediate H/S reactions. Repeated exposure to allergen Activation of mast cells : release of mediators . challenge .

24. primary يصدر من الماست سيل نفسهاand secondary من الخارج mediators عوامل الانفلاميشن:

25. Allergic reactions can be divided into immediate and late- phase responses . - the immediate response start within seconds and is due to preformed mediators. - the late reaction ,which takes up to 8-12 hours to develop , is due to induced synthesis and release of mediators & cytokines .

26. The late-phase response : due to synthesis of new mediators (PG,) LT.,) chemokines & cytokines, with Influx تدفقof eosinophils and T-cells . takes 8-12 hours to develop. The immediate response : due to preformed &rapidly synthesized Mediators . start within seconds.

27. clinical presentations : - allergic rhinitis . - allergic asthma . - skin allergy . - food allergy . - systemic anaphylaxis .

28. Allergic rhinitis : inhaled allergens activate mucosal mast cells beneath the nasal epithelium . mediators released . diffuse across the mucous membranes of the nasal passages .

29. The immediate reaction in allergic rhinitis is characterized by : 1. intense شديده itching & sneezing . 2. local edema (leading to blocked nasal passages). 3. nasal discharge سيوله ( typically rich in eosinophils ). 4.irritation تهيج of the nose ( as a result of histamine) .

30. A similar reaction to airborne allergens deposited تدخل in the conjunctiva of the eye can result in :allergic conjunctivitis.

31. Allergic asthma : inhaled allergens activate submucosal mast cells in the lower airways . mediators released within seconds & lead to : contraction of bronchial smooth muscles. (bronchial constriction – difficulty in breathing ). increased secretion of mucus . increased vascular permeability . influx تدفق of inflammatory cells ( including eosinophils & TH2 cells ).

33. An important feature of asthma is chronic inflammation of the airways . This result from the influx of inflammatory cells . TH2 cells . IL-9 & IL-13 . eosinophils . Major basic protein neutrophils . proteolytic E. Lung epith. Cells . Rantes & eotaxin . These cell products act on • Airway smooth muscle cells . • Lung fibroblasts . • 3. Mucous glands . and cause : airway remodeling .

34. Airway remodeling : Goblet cell metaplasia . thickening of the airway walls by hyperplasia & hypertrophy of the smooth muscle layer Development of fibrosis . Increased mucus permanent narrowing of the permanent secretion . airways . tissue damage. Irreversible lung damage .

35. smooth muscle contraction. mucus plug .

36. Hyperreactive airways react to non- specific factors: chemical irritants . smoke & Strong perfumes . sulphur dioxide & air pollutants. viral & bacterial respiratory infections .

37. Skin allergy : manifest as : - acute urticaria . - chronic eczema . * allergens enter the epidermis or dermis by : 1. a stinging insect . 2. direct contact . 3. through the blood ( ingested food or drug ).

38. local connective tissue mast cells become activated & release mediators . * mediators activate local increase in local nerve endings. vasc. permeability. - vasodilatation of extravasation of blood vessels. fluid from blood. ( redness of the skin. ) ( Swelling of the skin.) this skin lesion is called : wheal انتفاخ-and flare حمره reaction .

40. Acute urticaria: تنتشر حول الجسم كله a disseminated متبعثر form of the wheal-and- flare reaction . sometimes appear when ingested allergens enter the blood stream and reach the skin . Histamine released by mast cells in the skin causes : large , itchy red swellings of the skin. ( urticaria or hives ).

41. Acute urticaria :

42. Swelling of the lipsand eyes may be associated with urticaria .Angioedema :

43. Food allergy : A significant مهم health problem especially in children . In USA food allergy cause approximately 30,000 anaphylactic reactions each year , including 200 deaths . * food allergens resist مقاوم digestive enzymes & therefore reach the mucosal surface of the small intestine as an intact molecule .

44. Ingested allergens in food cause activation of mucosal mast cells in the gastrointestinal tract . mediators released . transepithelial fluid loss smooth muscle contraction. diarrhea . vomiting .

45. Ingested food allergens may enter the bloodstream and cause systemic reactions . activation of connective disseminated mast cell tissue mast cells in the activation . skin . urticaria . generalized anaphylaxis.

46. Systemic anaphylaxis ( anaphylactic shock). Allergens may be introduced directly into the bloodstream as a result of : - penicillin injection الدواء المحقون ( مهب شرط بنسلين ) . - honey-bee sting . disseminated منتشر mast cell activation . :اسباب شائعه لحدوثها

47. massive mediator release into the blood result in : wide spread increase airway swelling of the in vascular permeability . Constriction. larynx loss of blood pressure . difficulty in suffocation. (hypotension) . Breathing ( difficulty in breathing ). * العلاجthis condition can be rapidly fatal but can be controlled by immediate injection of epinephrine ( adrenaline ) .

48. Diagnosis : التشخيص 1. skin prick test (SPT). 2. specific IgE measurement . 3. challenge tests. 4. elimination – provocation tests. ( food allergy ).

49. skin prick test skin prick test .