Hypersensitivity Reaction - PowerPoint Presentation

1. Hypersensitivity ReactionDr Zahraa A Mohammed

2. Learning objectivesAfter reading this lecture, you should be able to:Distinguish between the four types of hypersensitivities, and understand the immunological mechanisms behind each of them.For each of the four types of hypersensitivities, recognize the harmful effects of these immune responses when they become inappropriately vigorous responses (hypersensitivity reactions).Discuss the roles of environmental factors and genetics in predisposition to allergies

3.

4. IntroductionHypersensitivity reaction: an abnormal state of immune reactivity that has deleterious effects for the host.Tissue injuryDiseasedeathAllergy: is often used to designate a pathological condition resulting from hypersensitivity, particularly when the symptoms occur shortly after exposure.

5. Classification of hypersensitivityHypersensitivity diseases are commonly classified according to thetype of immune response and the effector mechanism responsible forcell and tissue injury:Immediate (type I) hypersensitivityAntibody-mediated (type II) hypersensitivityImmune complex–mediated (type III) hypersensitivityT cell–mediated (type IV) hypersensitivity

6. IgE- mediated type I hypersensitivityis caused by IgE antibodies specific for nonmicrobial environmental antigens and is the most prevalent type of hypersensitivity diseaseImmediate hypersensitivity diseases, commonly grouped under allergy or atopy, are often caused by activation of interleukin-4 (IL-4), IL-5, and IL-13 producing Th2 cells and the production IgEantibodies, which activate mast cells and basiophils and induce inflammation

7.

8. Common components of type-I reaction

9. Allergen: Antigens that elicit immediate hypersensitivity reactions, these are proteins or chemical bound to protein. The important characteristics of allergens that, unlike microbes, they do not generally stimulate the innate immune responses that are associated with macrophage and dendritic cell secretion of TH1- and TH17-inducing cytokines.Chronic or repeated cell activation in the absence of strong innate immunity may drive CD4+ T cells preferentially toward the TH2 pathway. The chemical nature. include low to medium molecular weight, stability, glycosylation, and high solubility in body fluids. These structural features probably protect the antigens from denaturation and degradation in the gastrointestinal tract and allow them to be absorbed intact. Some nonprotein substances, such as penicillin, can elicit strong IgE responses, when react chemically with amino acid residues in self proteins to form hapten carrier conjugates, which induce IL-4–producing helper T cell responses and IgE production

10. IgE production

11. Mast cells and BasophilsTwo major subsets of mast cells have been described:. Mucosal mast cells have abundant chondroitin sulfate and tryptase, and little histamine are found in intestinal mucosa and alveolar spaces in the lungConnective tissue mast cells have abundant heparin and neutral proteases in their granules, produce large quantities of histamine, and are found in the skin and intestinal submucosaActivated mast cells secrete a variety of mediators that are responsible for the manifestations of allergic reactions.Basophils contain granules that bind basic dyes, and they are capable of synthesizing many of the same mediators as mast cells

12. IgE –binding receptor

13. Activation mast cells and basophils

14. Mediators of mast cellsPrimary mediators: Biogenic Amines and proteolytic enzymes Histamine acts by binding to target cell receptor(for example H1, H2, H3) expressed on different cell types. Upon binding to cellular receptors (for example H1), histamine induces constriction of intestinal and bronchial smooth muscles, increased peristalsis, increased permeability of venules and increased nasal secretionOther primary mediators that are exocytosed by mast cells and basophils include heparin,serotonin, carboxypeptidase A, cathepsin G, and neutral serine proteases.

15. Secondary mediators Lipid Mediatorsprostaglandin D2 (PGD2). Acts as a vasodilator and a bronchoconstrictor. PGD2 also promotes neutrophil chemotaxis and accumulation at inflammatory sites. leukotrienes its degradation products LTD4 and LTE4 which cause prolonged bronchoconstriction. (slow-reacting substance of anaphylaxis and are thought to be important mediators of asthmatic bronchoconstriction.platelet-activating factor (PAF) has direct bronchoconstriction actions. CytokinesActivated human mast cells secrete a variety of cytokines that alter the microenvironment and help in recruiting inflammatory cells such as eosinophils and neutrophils. Th e cytokines secreted by these cells include TNF-α, IL-1, IL-3, IL-4, IL-5, IL-6 and colony-stimulating factors (CSF). IL-4 increases IgE production while IL-5 is important in the recruitment and activation of eosinophils

16.

17.

18. Type I hyper. are characterized by both early and late responses1) The Immediate Reaction The early vascular changes that occur during immediate hypersensitivity reactions are demonstrated by the wheal-and-flare reaction) within minutes of allergen exposure, including the release of histamine, leukotrienes, and prostaglandins. 2) The Late-Phase ReactionThe immediate wheal-and-flare reaction is followed 2 to 4 hours later by a late-phase reaction consisting of the accumulation of inflammatory leukocytes, including eosinophils, basiophil,neutrophil and helper T cells

19. a wheal and-flare allergic reaction develops withina minute or two of intradermal injection of antigen and lasts for up to 30 minutes.The more widespread edematous response characteristic of the late phase develops approximately 6 hours later and can persist for some hours.The photograph shows an intradermal skin challenge with allergen showing a15-minute wheal-and-flare (early-phase)reaction (left) and a 6-hour late-phasereaction (right).

20. Genetic factors contribute to the development of lgE-mediatedallergic diseaseThe propensity to develop allergies is influenced by the inheritance of several genes.Atopy is an immediate hypersensitivity response that occurs only in genetically predisposed individuals upon sensitization to a specific allergenAtopic individuals have higher total levels of IgE in the circulation and higher levels of eosinophils than their non-atopic counterparts and are more susceptible to developing allergic diseases such as allergic rhino conjunctivitis, allergic asthma, or atopic eczema.

21. Clinical consequences of type-I hypersensitivityClinical consequences of type I hypersensitivity response vary greatly in severity and character from life-threatening conditions such as systemic anaphylaxis, to asthma and common forms of allergic reactions such as hay fever and eczema. Type –I reactions can be systemic or localizedSystemic AnaphylaxisAnaphylaxis is a systemic immediate hypersensitivity reaction characterized by edema in many tissues and a decrease in blood pressure, secondary to vasodilation. These effects usually result from the systemic presence of antigen introduced by injection, an insect sting, or absorption across an epithelial surface such as gut mucosa. The allergen activates mast cells in many tissues, resulting in the release of mediators that gain access to vascular beds throughout the body.The decrease in vascular tone and leakage of plasma caused by mast cell mediators can lead to a significant decrease in blood pressure or shock, called anaphylactic shock, which is often fatal. The cardiovascular effects are accompanied by constriction of the upper and lower airways, laryngeal edematreatment is systemic epinephrine, which can be lifesaving by reversing the bronco constrictive and vasodilatory effects of mast cell mediators

22. Localized hypersensitivity reaction (Atopy)Allergic asthma A more serious IgE-mediated respiratory caused by immediate- type hypersensitivity and late- phase allergic reaction. is triggered by allergen-induced activation of submucosal mast cells in the lower airwaysThis leads within seconds to bronchial constriction and an increased secretion of fluid and mucus, making breathing more difficult by trapping inhaled air in the lungs. Patients with allergic asthma usually need treatment, and asthmatic attacks can be life threatening

23. Allergic rhinitis or hay fever is the most common atopic disorder and a consequence of immediate hypersensitivity. It results from the reaction of inhaled airborne allergens such as plant pollens or dust mites, fungal spores and animal danders, with sensitized mast cells present in the upper respiratory tract (conjunctivae and nasal mucosa). Th e binding of allergen to these cells induces the release of pharmacologically active mediators from mast cells. Th ese mediators cause mucus secretions, localized vasodilation and increased capillary permeability. Th e symptoms of hay fever include mucosal oedema, watery exudation of conjunctivae, itching and tears in the eyes, as well as sneezing, coughing and difficulty in breathing. Anti histamines are used for treatment.Food allergy: a variety of food items can induce localized immediate hypersensitivity reactions. Allergen cross-linking of IgE present on intestinal mucosal and submucosal mast cells leads to release of mediators that induce enhanced peristalsis, increased fluid secretion from intestinal lining cells, vasodilation and often vomiting and diarrhea. Allergens might enter the blood stream from the gut and, depending on the fate of allergens, various symptoms can ensue. Some allergic individuals develop urticaria (hives), which may take hours to subside, other might develop wheal and fl are reaction on the skin, a reflection of the inflammatory events of the body. Wheal and flare response usually subsides aft er about 15 to 20 minutes. Allergic reactions can develop to varied types of food. Some of the most common food items that contain allergens include eggs, peanuts, milk and shellfish.Atopic dermatitis or eczema. Is a common skin disorder that are cause by a late- phase reaction to an allergen in the skin. The patients usually have high serum IgE level, increased number of eosinophils and TH2 cells in skin lesion. Atopic dermatitis is often treated with topical corticosteroids. Urticaria or hives another example of allergic reaction in the skin which is an acute wheal –flare reaction induced by mast cells mediators and occurs in response to direct local contact with an allergen

24. The pathophysiologic sequence in atopic asthma is probably initiated by mast cell activation in response to allergen binding to IgE as well as by TH2 cells reacting to allergens. The lipid mediators and cytokines produced by the mast cells and T cells lead to the recruitment of eosinophils, basophils, and more TH2 cellsAn important feature of asthma is chronic inflammation of the airways, which is characterized by the continued presence of increased numbers of TH2 lymphocytes, eosinophils, neutrophils, and other leukocytesThe concerted actions of these cells cause airway remodeling-a thickening of the airway walls due to hyperplasia and hypertrophy of the smooth muscle layer, with the eventual development of fibrosis. This remodeling leads to a permanent narrowing of the airways, and is responsible for many of the clinical manifestations of chronic allergic asthmaSmooth muscle cell hypertrophy and hyperreactivity are thought to result from leukocyte-derived mediators and cytokines. Corticosteroids may also be given systemically, especially once an attack is under way, to reduce inflammation and bronchial smooth muscle cell relaxants

25. Tests for diagnosis of type-I hypersensitivitySkin test :a small amount of the potential allergen is introduced at the specific skin site either by intradermal injection) or by a lancet or by superficial scratching. If the person is sensitive to the antigen, there israpid appearance of a raised red area, or wheal and fl are reaction. Th e wheal is caused by extravasation of serum from capillaries into the skin which results from the direct effect of histamine released by local activated mast cellsPatch test: to check if the patient has atopic dermatitis check whether the patient has atopic dermatitis or eczema

26. Control of Type 1Avoiding contactImmunotherapySubcutaneous injections of allergens(Hyposensitization)Causes shift to IgG production instead of IgEMonoclonal anti-human IgEThough expensive and difficult administer.Drug therapiesCan treated with pharmacological inhibitors of cellular and tissue responses and inflammation (antihistamines, leukotriene inhibitors and corticosteroids)