BSc INTRODUCTION TO ALLERGY JANUARY 2003

1. BSc INTRODUCTION TO ALLERGY JANUARY 2003

2. INTRODUCTION TO ALLERGY A Clinical Perspective

3. THE IMMUNE SYSTEM • Essential for a normal healthy life • Main function is to protect us against infection • Think of the benefits of immunisation • Sometimes the immune system can “go wrong”

4. THE IMMUNE SYSTEM CAN GO WRONG IN SEVERAL WAYS • Gell and Coomb’s classification of hypersensitivity • “Allergy” is the commonest way that the immune system can go wrong

5. GELL AND COOMB’S CLASSIFICATION OF THE HYPERSENSITIVIY STATES • TYPE 1 - Immediate, IgE mediated, anaphylactic • TYPE 2 - Cytotoxic • TYPE 3 - Immune complex • TYPE 4 - Delayed type hypersensitivity

6. EXAMPLES OF IgE MEDIATED ALLERGY • Hay fever – running eyes and nose during the pollen season • Asthma – attack might be brought on by contact with eg a cat • Peanut allergic patient may develop swelling of lips and a rash

8. Urticaria

9. Angioedema of mouth

10. When a substance is capable of producing allergic symptoms, it is known as an allergen

19. Such allergic reactions are common and are inconvenient rather than harmful

20. HOW COMMON IS ALLERGY? • Nearly half of all young adults show evidence in blood that they have the potential to develop this kind of allergy • Many of these people remain symptom free

21. OTHER NAMES FOR THIS TYPE OF ALLERGY • Type 1 allergy • IgE mediated allergy • Immediate type allergy • Atopy

22. People who suffer from Hay fever, asthma,and some types of eczema, usually have an immune system that reacts in an inconvenient way to one or more common substances in the environment

23. Antibody combining sites Light chains IgE Kappa or lambda εHeavy chains • Defence against parasites • Causes allergies • Small amounts in serum • Cytophilic to mast cells IgG IgM IgA IgE IgD Fc Mast Cell

24. IgE MEDIATED ALLERGY - IMMUNOLOGY (1) Y IgG, IgA, IgM Y Y Y Y B Y Y T

25. IgE MEDIATED ALLERGY - IMMUNOLOGY (2) Y Y IgE Y Y Some people produce IgE as well as the other classes of antibody. Y Y Y Y Y Y Y Y Y Y Y Y Y Y

26. IgE MEDIATED ALLERGY - IMMUNOLOGY (3) Y Y Y Y Y Y Y Y IgE is a “cytophilic” antibody. It attaches itself to mast cells in the tissues and basophils in the blood Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y

27. IgE MEDIATED ALLERGY - IMMUNOLOGY (4) Y Y Y sensitised mast cell Sensitised mast cells are harmless, however, they contain little granules of chemical messengers. These are not harmless when released into the circulation. Y Y Y Y Y

28. IgE MEDIATED ALLERGY - IMMUNOLOGY (5) Y Y Y sensitised mast cell The chemicals are not released into the circulation unless the IgE antibody surrounding the mast cell meets its antigen. Y Y Y Y Y

29. IgE MEDIATED ALLERGY - IMMUNOLOGY (6) Y Y Y sensitised mast cell meeting antigen Message is sent into mast cell telling it to degranulate and to start producing new chemicals Y Y Y Y Y

30. IgE MEDIATED ALLERGY - IMMUNOLOGY (7) Y Y mast cell degranulates Y Chemical messengers are released into the vicinity and some carried in the circulation. Y Y Y Y Y

31. IgE MEDIATED ALLERGY - IMMUNOLOGY (8) Histamine: Y Y Y Histamine is the main chemical messenger but there are others Constricts bronchioles Y Dilates blood vessels Y Y Increases vascular permeability Y Y

32. IgE MEDIATED ALLERGY - IMMUNOLOGY (9) Late response: This is largely due to attraction of eosinophils to the site and the release of active substances from them. Prolonged mucous secretion Oedema Persistent bronchial hyper-response

33. Types of t-helper cells IgE Y TH2 Y Y Y Y Y Some people produce IgE as well as the other classes of antibody. Y Y Y Y Y P Y Y Y Y Y TH1 B

34. IgE mediated allergy IgE Y TH2 Y Y Y Y Y Some people produce IgE as well as the other classes of antibody. Y Y Y Y Y P Y Y Y Y Y TH1 B

35. Th1 influence dominates TH1

36. TH1 cells • Produce gamma interferon • Produce tumour necrosis factor • Important in macrophage activation and phagocytic responses • Important in development of cell mediated immunity

37. Favours the non atopic NO IgE TH1

38. TH2 influence dominates TH2

39. Favours the atopic IgE TH2

40. TH2 CELLS • Produce interleukins 4,5,10,13 • Important in inhibition of macrophage activation • Important in the the development of IgE responses • Important in development of eosinophilia

41. What decides whether TH1 or TH2 dominates? TH2 TH1

42. Cytokine messages are sent to them, too! TH2 (IL-4) TH1(IL-12)

43. T-helper cell priming • Determined by cytokine milieu • IL-12 leads to TH1 responses • IL-4 leads to TH2 responses

44. Cytokines in allergy • TH2 cytokines • IL-4 and IL-13 are essential to regulation of IgE class switching • IL-5 is necessary for the differentiation, recruitment and activation of eosinophils

45. T- Helper cells in infancy • Infant thought to have a TH2 bias • Gradually diminishes during first two years of life in non allergic individual • Associated with maturing of IL-12 production • In allergic infants, reverse occurs • Is a TH1 stimulus necessary from the environment to avoid the development of allergic disease ?

46. Effect of Infections • Many bacterial infections enhance TH1 • Many viral infections enhance TH1 • Measles enhances TH2 • Helminths enhance TH2 strongly

47. ANAPHYLAXIS

48. WHAT IS ANAPHYLAXIS? • Anaphylaxis is the most severe form of IgE mediated allergy that exists • It is an immediate life-threatening reaction that requires urgent treatment

49. THE URGENCY OF ANAPHYLAXIS • The urgency of anaphylaxis is such that a patient could die before qualified help is available • It is very important therefore, that patients and also their relatives and know how to observe and if necessary give treatment before symptoms become life-threatening.

50. Fortunately… • The severest form of anaphylaxis is very uncommon • Anaphylaxis responds very well to treatment with adrenaline • Death from anaphylaxis is very rare.