11 10/6/2015 Hypersensitive Reactions Allergies Hugh B. Fackrell

22 10/6/2015 Hypersensitive Reactions l Assigned Reading l Content Outline l Performance Objectives –Key terms –Key Concepts l Short Answer Questions

33 10/6/2015 Assigned Reading l Chapter: 17 pp l Janis Kuby’s Immunology 3rd Ed

44 10/6/2015 Content Outline Gell & Coombs Classification l Type I Hypersensitivity: IgE mediatiated l Type II Hypersensitivity: Antibody mediated cytotoxic l Type III Hypersensitivity: Complex mediated cytotoxic l Type IV Hypersensitivity: DTH mediated

55 10/6/2015 Type I Hypersensitivity: IgE mediatiated l Components l Mechanisms l Mediators l Consequences l Regulation l Detection l Therapy

66 10/6/2015 Components l Allergens l IgE l Mast cells & basophils l IgE binding receptors

77 10/6/2015 House dust mite l Mite fecal pellets are the major source of the allergen in house dust

88 10/6/2015 Cat Hair l Major cause of allergies

99 10/6/2015 Pollen

10 10/6/2015 Type I Hypersensitivity

11 10/6/2015 Mechanisms l receptor cross linkage l Intracellular events

12 10/6/2015 Mechanism of Latex Allergy l 3 step process l sensitization l Activation of mast cells l Prolonged immune activity

13 10/6/2015 Sensitization to Latex Proteins l Macrophage presents Ag to T cells l T cells activate B cells via IL-4 l B cells become plasma cells make IgE l IgE attaches to mast cell receptors

14 10/6/2015 Activation of Mast cells l Allergen binds to IgE on mast cell l Intracellular enzyme cascade –immediate release of histamines cytokines l Induction of intracellular lipids –Prostoglandins, arachadonic acid

15 10/6/2015 Chemical released by activated mast cells induce basophils and other cells in the bloodstream to migrate into the tissue. These cells sustain immune activity which leads to tissue damage Prolongation of Immune Activity

16 10/6/2015 Allergen Activation

17 10/6/2015 Mediators l histamine l leukotriens & prostoglandins l cytokines

18 10/6/2015 Consequences l systemic anaphylaxis l localized anaphylaxis l late phase reaction

19 10/6/2015 Atopic Eczema

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22 10/6/2015 Anaphylatic Response to Bee venom

23 10/6/2015 Early vs late Response

24 10/6/2015 Detection

25 10/6/2015 Skin Patch Test

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32 10/6/2015 Latex Questionaire Positive History l RAST positive Avoid latex l Rast Negative è Patch tests Positive Identify allergen è Patch tests Negative Treat dermatitis Negative History l RAST positive è Latex test positive Avoid latex è latex test negative powder free gloves l Rast negative Safe to use latex

33 10/6/2015 Therapy l Hyposensitization –IgG as blocking antibody »repeated subcutaneous injections –T cell anergy »soluble antigens l Antihistamines

34 10/6/2015 Drugs for Type I hypersenstivity l Antihistamines blocks receptors l Cromolyn sodium blocks Ca++ influx l Theophylline –inhibits phosphodiesterase –[cAMP] kept high l Epinephrine –stimulates cAMP via beta adrenergic receptors l Cortisone –blocks conversion of histidine to histamine

35 10/6/2015 Performance Objectives

36 10/6/2015 Key Terms l allergen, allergy, anaphylactic shock,anaphylaxis, anergy, atopy, basophils, l contact sensitivity, degranulation, delayed type hypersensitivity, l desenstization, granulomas, homocytotropic antibodies, hypersensitivity,

37 10/6/2015 l hyposensitivity, immediate hypersensitivity, late phase reaction, mast cells, l sensitization, senstizing dose, shocking dose, systemic anaphlyaxis, triple response: edema, erythema, wheal and flare, l tubercles, tuberculin skine reaction, tuberculosis, Type I hypersensitivity, l Type II hypersensitivity, Type II hypersensitivity, Type IV hypersensitivity.

38 10/6/2015 Key Concepts l List the Gell & Coombs classification for hypersensitivity reactions; give examples of each type. l Describe stimulatory hypersensitivity and give a specific example l Discuss the difference between primary and secondary exposure to antigen in imunity and in hypersensitivity

39 10/6/2015 l Describe the structural and functional characteristics of IgE. l Discuss the cytotropic nature of IgE l Differentiate betweeen the cyclooxygenase and lipoxygenase pathways of mediator production

40 10/6/2015 l Describe the role of mast cells in immediate hypersensitivity reactions. l Distinguish between release of preformed and newly formed mediators from mast cells and give examples of each type of mediator l Discuss the hallmarks of delayed type hypersensitivity

41 10/6/2015 l Explain the mechanisms of Delayed Type Hypersensitivity induction and development l Distinguish between different types of Delayed type hypersensitivity. l Describe tuberculosis in terms of hypersensitivity reactions.

42 10/6/2015 Short Answer Questions

43 10/6/2015 l By derivation, what does allergy mean and what does hypersensitivity mean? Are they synonymous? l The main difference between immediate and delayed types of hypersensivitiy is the time of appearance of the reactions. True/False? If false, name the main differences. l What is the type II reaction described by Gell & Cooombs? Does this reaction require complement?

44 10/6/2015 l Is there a tendency to immediate hypersenstivity reactions? Explain? l Differentiate between antigen and allergen. l What immune and nonimmune cells are involved in immediate hypersensivity?

45 10/6/2015 l What class of antibody in responsible for immediate hypersenstivity? Describe some structural and biological characteristics of this antibody? l What do we mean by homocytotropic antibodies? l Briefly describe the result of the interaction of IgE, with mast cells –a) in the presence of allergen. –b) in the absence of allergen.

46 10/6/2015 l What are the chemical mediators of immediate hypersentivity reactions? l Some effector molecules of immediate hypersensitivity reactions are preformed mediators; others are newly synthesized mediators. Distinguish between the two. l Briefly describe the two pathways for the production of newly synthesized mediators.

47 10/6/2015 l How can you determine whether a person is allergic to a foreign protein? l What is the triple response? Name two "in vitro" tests. l What is the mechanism for desensitization for immediate hypersensitivities? Is this desensitization lifelong? If not speculate on the reasons. What are some other modes of treatment for immediate hypersensitivity?

48 10/6/2015 l Describe the differences between systemic anahylaxis and atopy? l Are the mechanisms of cell-mediated immunity and DTH the same? l Name the effector cells in DTH. l What are some of the hallmarks of DTH reactions?

49 10/6/2015 l Describe contact sensitivity. l How does contact sensitivity differ from the tuberculin skin reaction? l What is the mechanism of the tuberculin skin test? If the test is positive what causes the induration (hardening) of the test site? What substances are used in this test?

50 10/6/2015 DONE!!!