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Understanding Hypersensitivity Reactions in Immunology

Explore definitions and concepts of hypersensitivity, allergies, and immune responses in pharmacy students' study. Learn about types and clinical manifestations of hypersensitivity reactions.

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Understanding Hypersensitivity Reactions in Immunology

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  1. Immunology/ Pharmacy Students • Hypersensitivity Dr. Mohammad Odibate Department of Microbiology and immunology Faculty of Medicine, Mu’tah University

  2. Some Definitions and Concepts • Hypersensitivity: • Suggests Heightened Response • Is a set of undesirable reactions produced by the normal immune system, including allergies and autoimmunity. These reactions may be damaging, uncomfortable, or occasionally fatal. • Allergy: Generally refers to Type I Immediate Hypersensitivity; • Atopic Allergy, Atopic Individual, Atopy: • Genetic misregulation of IgE response (or) • Is an inherited tendency to respond to naturally occurring inhaled and ingested allergens with continued production of IgE • Immediate Hypersensitivity: • Within minutes (Type I) • or hours (Types II and III) • Delayed: • Takes two or more days • Phylaxis: Protection • Anaphylaxis: Opposite of Protection; Damaging

  3. Definition of hypersensitivity Immune response Good side Of the immune response Bacteria Bad side of the immune response Viruses Bad side of the immune response = an unwanted immune response that negatively affect the body systems = Hypersensitivity

  4. Hypersensitivity reactions= Policeman and the thief Ag Type 1 hypersensitivity Type 2 hypersensitivity Type 3 hypersensitivity

  5. Classification Type II Soluble Ag Type I Releasing of inflammatory mediators Soluble Ab Cell with fixed Ab on its surface Complement mediated tissue destruction Cell with Ag on its surface Type III Type IV T-cell Soluble Ab Soluble Ag Mediate tissue destruction Complement mediated tissue destruction Tissue

  6. Type I Hypersensitivity The distinguishing feature • Seconds to minutes between exposure to antigen and the appearance of clinical symptoms • The key reactant is IgE • Antigens that trigger formation of IgE are called atopic antigens, or allergens The prerequisites for triggering type I hypersensitivity Two factors should be available to trigger the type I hypersensitivity • The availability of specific MHC (HLA) antigens such as HLA-DR2, DR4, and DR7 • The presence of specific TCR to the processed allergen on the surface of APC • The naïve T cell will be activated and differentiated into TH2 cell • TH2 cell will start producing different types of cytokines that eventually mediate the type I hypersensitivity

  7. Prerequisites for Ab production 1 Specific MHC 2 Ag complexed with MHC 3 Specific TCR B cell TH2 cell naïve T cell

  8. Prerequisites for Ab production Mohammad Ahmad Ali Flower Pollen Grain naïve T cell naïve T cell naïve T cell No MHC molecules specific for the processed allergen No TCR specific for the processed allergen

  9. Type I hypersensitivity Regional lymph node Flower Pollen Grain APC IgE APC T B Mast cells & Basophils

  10. Common Antigens Associated with Type I Hypersensitivity

  11. Mechanism of mast cell degranulation Primary exposure To an allergen Induction of IgE Production Binding to Mast & basophills Secondary exposure To the same allergen

  12. Pathogenesis of Type I Hypersensitivity PG Allergen Secondary exposure Inside Tracheal mucosa Submucosa Processing and Presentation APC MHC B cell TH2 cell Releasing of type I hypersensitivity mediators IL-4 IL-13 IgE

  13. Penicillin triggering Type I Hypersensitivity + This will activate an immune response to produce anti-penicillin IgE antibodies Penicillin An individual has MHC and TCR capable of binding to penicillin penicillin will bind directly to the IgE which will Activate mast cell degranulation Secondary exposure to penicillin IgE antibodies will bind to the mast cells

  14. Functions of the type I hypersensitivity mediators

  15. Clinical manifestations of type I hypersensitivity The clinical symptoms varies from Localized response Systemic response anaphylaxis • Digestive tract: contact results in vomiting, cramping, diarrhea. • Skin sensitivity: usually reddened inflamed area resulting in itching. • Airway sensitivity: results in sneezing and rhinitis OR wheezing and asthma. • Systemic vasodilatation • Smooth muscle contraction leading to severe bronchiole constriction • Edema which might lead to Shock- coma- and death

  16. Clinical manifestations of type I hypersensitivity

  17. Clinical responses Urticaria/angioedema: • Release of the above mediators in the superficial layers of the skin can cause pruritic wheals (suface swelling in the skin) with surrounding erythema. • If deeper layers of the dermis and subcutaneous tissues are involved, angioedema results. Allergic rhinitis (nasal inflammation): • Sneezing, itching, nasal congestion, rhinorrhea, and itchy or watery eyes. Allergic asthma: • Release of the above mediators in the lower respiratory tract can cause bronchoconstriction, mucus production, and inflammation of the airways, resulting in chest tightness, shortness of breath, and wheezing.

  18. Testing for Immediate Hypersensitivity 1- In Vivo Skin Tests: Skin Prick Test 2 1 +ve control -ve control Suspected allergen One drop of 1 mg/ml histamine One drop of the diluent used to preserve the allergen extract.

  19. Testing for Immediate Hypersensitivity 1- In Vivo Skin Tests: Skin Prick Test Results HD: House Dust The person is considered allergic (+ve result) when the allergen diameter on the skin is 3mm more than the –ve control. In this case the injected material is called allergen

  20. Testing for Immediate Hypersensitivity 2- In Vitro Tests to determine the total IgE (ELISA) Substrate HRP Sandwich ELISA Anti human IgE Product (different color intensity) Patient serum suspected of having IgE Anti-human IgE Substrate Anti-human IgE Product (different color intensity) Indirect ELISA Patient serum suspected of having IgE Known allergen

  21. Treatment of type I hypersensitivity • Treatment by drugs • Anti-histamine, leukotrienes antagonists, corticosteroids • For anaphylactic shock; IM adrenaline, IV anti-histamine and corticosteroids. • Humanized monoclonal Anti-IgE 2. Treatment by immunotherapy • Its based on regular injections or sublingual treatment with increasing doses of allergen over months (induces tolerance). • Used for seasonal hay fever and anaphylactic sensitivity to venom of bees and wasps • The response includes : -Increase IgG4

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