type i: ige-mediated immediate hypersensitivity
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Type I: IgE-Mediated Immediate Hypersensitivity
Localized and Systemic AnaphylaxisUpdated: December 01, 2015
Folder Title: IgEAllerNoTP
Chapter 15, 7th Edition, Kuby Immunology, pp 485 to 516
This is a Turning Point Slide to Open the System to Accept Your Transmitted
Questions. No need to answer.
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Immunology and MedicineTopics 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 447Cytokines, 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 20th 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 toxinCatastrophe!Got the opposite of protection
Not phylaxis (protection)But ana-phylaxis (opposite of protection)
Notes on animal experimentationNotes on how Science and Medicine proceed
Some Definitions and Concepts"Hypersensitivity" - Suggests Heightened Response
Includes in-appropriate or mis-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
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 complexesGet deposition of AgAb Complexes in tissues and organsGet Inflammatory Damage
What if the antigen is an auto-antigen?Cannot be clearedGet chronic inflammatory responseRheumatoid Arthritis
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
AllerIsStart Here, Tuesday Dec. 1, 2015
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 DanderAllergy1
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)
Non-IgE Antibody-related Initiators of Type I Hypersensitivity
Complement Activation Products:
C3a, C4a, C5a
"Anaphylotoxins"
Various Drugs: ACTH, Codeine,
Morphine, Penicillin
NonIgE
Underlying Mechanism of Type I Allergy:Calcium influx into Mast Cell. Triggering of degranulation
Bound IgE and Allergen Not Required
To here: Nov. 15, 2014
Topics in Type I Immediate Hypersensitivity That we Need to Address:
Mediators that cause Mast Cell/Basophil Immune Responses and Type I Hypersensitivity
How Do We Control Type I Immediate Hypersensitivity?
Why do we have Type I Mast Cell Degranulation Responses Anyway?
Mediators of Type I Hypersensitivity:Stored in Mast Cell Granules
(See Table 16-3, Immunology, 5th Edition, p. 370)Primary Mediators of Type I Hypersensitivity
Histamine, Heparin and Serotonin Increased vascular permeability;
Smooth Muscle Contraction
Chemotactic Factors for
Eosinophils and Neutrophils Attract Eosinophils & Neutrophils
Proteases Degrade Basement membranes of blood vessels;
Activate bronchial mucous secretions;
Activate Complement
Secondary Mediators of Type I Hypersensitivity:Synthesized and Released After Mast Cell Activation
(See Table 16-3, Immunology, 5th Edition, p. 370)
Platelet Activating Factor Platelet Aggregation& Degranulation; Smooth muscle contraction
Prostaglandins Vasodilation; Smooth muscle contraction
Leukotrienes (SRS-A)* Increased vascular permeability; Pulmonary smooth muscle contraction
(*SRS-A : Slow Reacting Substance of Anaphylaxis)
Bradykinin Increased vascular permeability; Smooth muscle contraction
Cytokines: Systemic Anaphylaxis; (IL1 & TNF-a; Others*) Altered Cell adhesion* See Slide 42
Overview of Mast Cell Mediated Type I ImmediateHypersensitivity: Triggering of Sensitized Cells and Release of
Early and Late Mediators(From Roitt, Brostoff, and Male, Immunology, 4th Ed., Fig 22.14)
Overview of Mast Cell Mediated Type I ImmediateHypersensitivity: Triggering of Sensitized Cells and Release of
Early and Late Mediators:How Do We Treat This???
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 Influxa. Keep cyclic AMP (cAMP) from Falling Theophylline b. Increase production of cAMP: Adrenaline
Why Basic Biological Mechanisms Matter in Medicine
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
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 BiologyApplications to Therapeutic Intervention
This is to introduce the concept of intra-cellular signal transduction triggered by extra-cellular signals and cell surface receptors.
Details will not be asked.Major concept being illustrated is important
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Response Counter
Why do we get Type I Immediate Hypersensitivity Reactions in so many
different sites or even systemically?(Short answer slide)
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Meanings and Concepts Associated with Type I and Type IV Hypersensitivity
Atopic Allergy (Atopic Individual): Genetic misregulation of IgE production or response (Type I)
Type IV Delayed Type T-Cell-Mediated Hypersensitivity
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
An Example of Signal Transduction: Type I Allergy Signal Transduction Cascade.(Details not to be memorized. Concept of Signal Transducxtion is Illustrated
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