Podcast
Questions and Answers
What is the antigen that stimulates an IgE antibody response and causes an allergic reaction called?
What is the antigen that stimulates an IgE antibody response and causes an allergic reaction called?
What chronic respiratory condition is primarily associated with Type I hypersensitivity reactions?
What chronic respiratory condition is primarily associated with Type I hypersensitivity reactions?
Which term describes the propensity of some individuals to develop IgE-mediated antibodies to allergens?
Which term describes the propensity of some individuals to develop IgE-mediated antibodies to allergens?
What percentage of the population in developed countries is estimated to be atopic?
What percentage of the population in developed countries is estimated to be atopic?
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What happens during anaphylaxis if it is not treated immediately?
What happens during anaphylaxis if it is not treated immediately?
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What is the Gell & Coombs classification for Type I hypersensitivity reactions?
What is the Gell & Coombs classification for Type I hypersensitivity reactions?
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Which type of hypersensitivity reaction involves IgG or IgM antibodies recognizing antigens on cells or tissues?
Which type of hypersensitivity reaction involves IgG or IgM antibodies recognizing antigens on cells or tissues?
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What type of immune response is common to all hypersensitivity reactions?
What type of immune response is common to all hypersensitivity reactions?
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Which type of hypersensitivity reaction is characterized by an immune complex (IgG + soluble antigen)?
Which type of hypersensitivity reaction is characterized by an immune complex (IgG + soluble antigen)?
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In the context of hypersensitivity, what does 'sensitization to the antigen' refer to?
In the context of hypersensitivity, what does 'sensitization to the antigen' refer to?
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Which of the following statements about Type IV hypersensitivity is true?
Which of the following statements about Type IV hypersensitivity is true?
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What is required for a hapten to elicit a hypersensitivity reaction?
What is required for a hapten to elicit a hypersensitivity reaction?
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Which type of hypersensitivity can result in conditions such as allergic asthma?
Which type of hypersensitivity can result in conditions such as allergic asthma?
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Study Notes
Overview of Hypersensitivity Reactions
- Hypersensitivity reactions (HSR) occur when the normal immune system produces a heightened reaction to an antigen. This reaction can be harmful or even fatal.
- The Gell & Coombs classification categorizes hypersensitivity reactions into four types (I-IV).
- Type I hypersensitivity is also known as allergy/anaphylaxis/atopic. Involves IgE antibodies.
- Type II hypersensitivity involves antibodies (IgG or IgM) binding to cells or tissues.
- Type III hypersensitivity involves immune complexes.
- Type IV hypersensitivity is also known as delayed-type hypersensitivity and involves T cells.
Lecture Objectives/Lecture Organization
- The lecture aims to identify and differentiate the four types of hypersensitivity reactions (I-IV).
- It will detail the immunologic mechanisms underlying each type.
- The lecture will also discuss the pathogenesis of each type's hypersensitivity reactions.
Hypersensitivity Type I Reactions
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- The lecture will cover the immunological mechanisms behind Type I hypersensitivity reactions.
- A case study on allergic asthma will be presented.
Some Definitions
- Allergy: An altered reactivity to an antigen, typically innocuous.
- Allergen: A substance that stimulates an IgE antibody response and causes an allergic reaction.
- Atopy: A tendency to develop IgE-mediated antibodies to allergens; common in developed countries, and incidence is increasing 2-3 fold in the last 30 years.
- Hives (Urticaria): Itchy, raised swellings on the skin associated with allergic reactions.
- Asthma: A chronic respiratory condition causing difficulty breathing; often, but not always, connected to allergies (Type I).
- Anaphylaxis: An immediate, life-threatening systemic allergic reaction.
Common Sources of Allergens
- Inhaled materials: Plant pollens, animal dander, mold spores, and house dust mites.
- Injected materials: Insect venoms, vaccines, and drugs.
- Ingested materials: Foods, orally administered drugs, and shellfish.
Three Phases of an Allergic Reaction
- Sensitization: Production of allergen-specific IgE that binds to IgE Fc receptors on mast cells and basophils.
- Activation: Re-exposure to the allergen cross-links the IgE receptors, triggering rapid degranulation, releasing potent inflammatory mediators.
- Effector: The response to inflammatory mediators results in clinical manifestations such as rhinitis (hay fever), hives (urticaria), asthma, and anaphylaxis.
Sensitization - Development of an IgE Response to Allergens
- Allergens' entry through mucosal surfaces initiates a primary response in lymphoid tissue.
- TH2 response (IL-4 & IL-13) favour IgE production.
- Conventional immunotherapy alters the balance toward CD4+TH1 cells.
- Mast cells, basophils, and activated eosinophils have high-affinity IgE receptors (FcεR1).
Activation Phase – Re-exposure to the Allergen
- Multivalent antigens crosslink IgE receptors on mast cells.
- Rapid events: Receptor aggregation and changes in membrane fluidity trigger transient increase in cAMP and influx of calcium ions.
- Granules fuse with the cell membrane, leading to degranulation and release of potent inflammatory mediators.
Effector Phase
- Preformed mediators (e.g histamine, heparin, proteases) and newly synthesized mediators (e.g., leukotrienes) are released and cause inflammation.
Hives or Urticaria
- Wheal: Swelling due to increased vascular permeability.
- Flare: Redness due to vasodilation and increased blood flow.
- Allergy skin prick tests help identify allergens.
IgE-Mediated Late Phase Reaction
- Allergic reactions have both immediate and late responses.
- Allergic asthma can involve a measurable reduction in FEV (forced expiratory volume) during an allergic reaction, as seen by a graph.
Anaphylaxis
- Anaphylaxis is a serious, potentially life-threatening allergic reaction.
- Symptoms: Include respiratory distress, swelling, itching, stridor, hypotension and collapse.
- Treatment: Immediate administration of epinephrine (adrenaline) is vital.
Hypersensitivity Type II Reactions
- Antigens: Located on the surface of cells or tissues.
- Antibodies: IgG or IgM that directly bind to these cellular antigens.
- Mechanisms: Complement-mediated reactions, antibody-dependent cell-mediated cytotoxicity (ADCC), and stimulatory anti-receptor antibodies.
- Examples: Transfusion reactions (ABO incompatibility, Rh incompatibility), hemolytic disease of the newborn, drug-induced reactions, and autoimmune reactions.
Hypersensitivity Type III Reactions
- Formation of soluble immune complexes: This can be systemic or localized.
- Antigens: May include foreign proteins, microbial antigens, or modified self-antigens (like certain drugs).
- Mechanism: Immune complex formation activates complement and inflammatory response; leads to activation of effector cells, particularly neutrophils.
- Immune complexes are normally cleared from the circulation by C3 receptors. Deficiencies in the complement system can cause immune complex diseases.
- Examples: Serum sickness, systemic lupus erythematosus, and localized immune complex reactions like Farmer's lung.
Hypersensitivity Type IV Reactions (Delayed-Type Hypersensitivity)
- Sensitization: Exposure to an antigen induces differentiation of antigen-specific TH1 memory cells.
- Elicitation. Re-exposure to antigen activates TH1 memory cells, leading to chemokine and cytokine production, recruitment of macrophages, and inflammation.
- Clinical Variants: Tuberculin-type hypersensitivity, contact hypersensitivity, granulomatous hypersensitivity, and allograft rejection.
- Examples: Tuberculin reaction (Mantoux test), contact dermatitis, and hypersensitivity to certain metals, latex, or poison ivy.
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Description
This quiz covers the fundamental concepts of hypersensitivity reactions, detailing the Gell & Coombs classification of types I-IV. Participants will learn to identify and differentiate each type based on the underlying immunologic mechanisms and pathogenesis involved. Ideal for students studying immunology or related fields.
