Presentation on theme: "Type I: IgE-Mediated Immediate Hypersensitivity Localized and Systemic Anaphylaxis Updated: November 18, 2014 Folder Title: IgEAllerNoTP Chapter 15, 7."— Presentation transcript:
Type I: IgE-Mediated Immediate Hypersensitivity Localized and Systemic Anaphylaxis Updated: November 18, 2014 Folder Title: IgEAllerNoTP Chapter 15, 7 th Edition, Kuby Immunology, pp 485 to 516
Immunology and Medicine Topics in Immunology and Medicine Planned for Coverage in BIO 447 Allergy – Hyper-sensitivity (Chapter 15) Immunity to Infectious diseases (Chapter 17) Vaccines (Chapter 17) Topics in Immunology and Medicine not Covered in BIO 447 Cytokines, Cytokine-based Diseases and Cytokine-Based Therapies (Chapters 4) Tolerance and Auto-immunity (Chapter 16) Transplantation Medicine (Chapter 17) Immune Deficiency Diseases e.g AIDS (Chapter 20) Genetics and the Immune Response – The MHC System (Chapter 8) In Biology of Cancer (BIO 501) Immunology and Cancer: In BIO 501, the Biology of Cancer Course (Chapter 21)
Portier and Richet: Discovery of Anaphylaxis (Early 20 th Century) Can We Treat Jellyfish Toxin poisoning the way we do for Diphtheria Toxin or Rabies Toxin ? Generate and antibody to the toxin? Make anti-toxin antibody in dogs: Inject Jellyfish toxin at sub-lethal levels into dogs. Give secondary booster injection with minute amount of toxin Catastrophe! Got the opposite of protection Not phylaxis (protection) But ana-phylaxis (opposite of protection) Notes on animal experimentation Notes on how Science and Medicine proceed
Some Definitions and Concepts "Hypersensitivity" - Suggests Heightened Response Includes in-appropriate ormis-regulated response "Allergy“: Generally refers to Type I Immediate Hypersensitivity; But also hear Types II and III "Allergy“ “Atopic” Allergy (Atopic Individual): Genetic misregulation of IgE production or response "Immediate"-Within minutes (Type I) or hours (Types II and III) "Delayed" - Takes two or more days "Phylaxis" - Protection "Anaphylaxis" - Opposite of Protection; Damaging Link to American College of Allergy, Asthma & Immunology http://www.acaai.org
Four Types of Hypersensitive (Allergic) Responses Also 15-1, 7th Edition
Note on Type III: Antigen-Antibody Mediated Allergy Excess antigen produces large amount of small antigen-antibody complexes because of excess antigen. Difficult for phagocytic cells to clear immmune complexes Get deposition of AgAb Complexes in tissues and organs Get Inflammatory Damage What if the antigen is an auto-antigen? Cannot be cleared Get chronic inflammatory response Rheumatoid Arthritis
Penicillin & Hypersensitivity Penicillin can induce all four types of Hypersensitive Reactions
What Determines Allergic Sensitivity? The Allergen (the immunogen) Dose of Allergen Route of Exposure or Administration Presence or absence of "adjuvants" (i.e. things that make allergy worse) Host Genetics AllerIs
Common Antigens Associated with Type I (Mast Cell & IgE or IgE-Receptor-Mediated) Hypersensitivity (Table 17.2 Kuby, 3rd Ed.) Proteins: Foreign Serum; Vaccines Plant Pollens: Rye Grass, Ragweed, Timothy, Birch Drugs: Penicillin, Sulfonamides, Salicylates, Anesthetics ACTH, Codeine, Morphine Foods: Nuts, Seafood, Eggs, Peas, Beans, Peanuts Insect Products: Bee, Wasp, or Ant Venom Mold Spores Animal Hair and Dander Allergy1
Foreign Serum Vaccines Also Table 15-1, 7 th Edition, p. 487
Type I Immediate Hypersensitivity: The Role of the Route of Exposure
Testing for and Measuring Type I Immediate Hypersensitivity
Atopic Urticaria ("Wheal and Flare" Reaction) Edematous - Swollen, Fluid-Influx "Wheal" Erythrematous - Reddened, Vasodilated, Blood-cell Influx "Flare" Manifestation of Type I Hypersensitivity in Skin: "Hives" Used for Skin Testing of Allergens (See Figure 15-10, Kuby, 6th Edition)
Overview of Mast Cell Mediated Type I Immediate Hypersensitivity: Triggering of Sensitized Cells and Release of Early and Late Mediators (From Roitt, Brostoff, and Male, Immunology, 4th Ed., Fig 22.14) IgEOView
Overview of Mast Cell Mediated Type I Immediate Hypersensitivity: Triggering of Sensitized Cells and Release of Early and Late Mediators: How Do We Treat This??? IgEOView
Approaches to Control of Type I Hypersensitivity Reponses
To Treat Type I Immediate Hypersensitivity Based on the Underlying Mechanisms: 1.Block Effects of Primary Mediators on Target Cells (e.g. respiratory smooth muscles or vascular endothelium) : Antihistamines; Cortisone 2.Block Calcium Ion Influx: Cromolyn 3.Block the Effects of Calcium Ion Influx a. Keep cyclic AMP (cAMP) from Falling Theophylline b. Increase production of cAMP: Adrenaline Why Basic Biological Mechanisms Matter in Medicine
How Can We Prevent or Over-ride This IgE- Mediated Immediate Hypersensitivity?
Desensitization to Type I (IgE-Mediated)Immediate Hypersensitivity: Isotype-Switching from IgE to IgG
Association of Economic Status with Type I Immediate Hypersensitivity Allergy: The Role of Environmental Multicellular Agents
Why is IgE Causing All This Trouble? ADCC-Mediated anti-parasitic Attack
Here is a question no reasonable Prof would ask in an Exam in Immunobiology: “List all of the primary and secondary mediators of Type I hypersensitivity that you can remember”. (If you need to know that kind of thing, search it on your favorite information source. That’s safer anyway, especially if you are trying to treat a patient.)
Here are questions that get to the heart of understanding and that really matter in the real world of medicine: (You can’t look something up if you don’t know enough to realize that the question exists and matters) “What is the fundamental difference between primary mediators of hyper-sensitivity and secondary mediators?” In terms of therapy, why does it matter whether something is a primary mediator or a secondary mediator of Type I immediate hypersensitivity? Give an example of a primary mediator of Type I hypersensitivity.
Signal Transduction Mechanisms Underlying Type I Hypersensitivity and Managing the Pathology Signal Transduction in Biology Applications to Therapeutic Intervention
An Example of Signal Transduction: Type I Allergy Signal Transduction Cascade. (Details not to be memorized. Concept of Signal Transducxtion is Illustrated
How Well Are You Following What is Being Presented at the Moment? (This is being set to “Anonymous”. Your name will not be linked to your response) 1.I am totally lost 2.I am having a hard time but I follow some of it. 3.I’m doing OK. I follow some of it. I’ll figure the rest out later. 4.I’m following very well. 5.This is not hard to follow. Please move on!
Meanings and Concepts Associated with Type I (and Type IV) Hypersensitivity Atopic Allergy (Atopic Individual): Genetic misregulation of IgE production or response Atopic Dermatitis (Allergic Eczema): Skin reaction from TH2-Type Helper T-Cells, IL4 production, and Eosinophil Influx Erythrematous (reddened, inflamed) White-cell Influx and Exudate (pus) Contact Dermatitis: Delayed-type (Type IV) Hypersensitivity TH1-Type Helper T-cells, Cytokines, Macrophage Influx e.g. Rubber-sensitivity, Poison Ivy, Poison Oak Dermal
Turning Point Quiz Question Please put away all devices and notes other than the NXT device.