Type I Hypersensitivity: Immediate Reactions

Podcast

Play an AI-generated podcast conversation about this lesson

Download our mobile app to listen on the go

Get App

Questions and Answers

In the context of Type I hypersensitivity reactions, which of the following scenarios would MOST significantly exacerbate the degranulation of mast cells, leading to acute allergic symptoms?

Pre-treating mast cells with a monovalent hapten that binds to IgE without cross-linking. (correct)
Exposure to an allergen in conjunction with a non-specific inhibitor of phospholipase A2.
Incubation of mast cells with IgG4 antibodies specific to the allergen prior to allergen exposure.
Introduction of an allergen that selectively activates inhibitory FcγRIIB receptors on mast cells.

A patient presents with glomerulonephritis, exhibiting granular deposits of C3 and IgG along the glomerular basement membrane. Further analysis reveals elevated levels of anti-streptolysin O antibodies (ASO). Which of the following mechanisms BEST explains the pathogenesis of this condition?

Deposition of pre-formed, small immune complexes in the glomeruli, leading to complement activation and neutrophil infiltration.
T cell-mediated delayed-type hypersensitivity reaction involving the release of cytokines and activation of macrophages within the glomeruli.
Direct antibody-mediated cytotoxicity against glomerular cells expressing streptococcal antigens, resulting in cell lysis and inflammation.
In situ formation of immune complexes within the glomeruli due to planted streptococcal antigens, activating the classical complement pathway. (correct)

A researcher is investigating novel therapeutic strategies for Type IV hypersensitivity reactions. Which of the following interventions would MOST effectively suppress the effector phase of a Mantoux reaction in a subject previously sensitized to tuberculin?

Systemic depletion of CD4+ T cells using a monoclonal antibody specific for CD4 prior to tuberculin injection. (correct)
Administration of a TNF-α antagonist, such as etanercept, prior to tuberculin injection.
Intravenous infusion of high-dose intravenous immunoglobulin (IVIG) immediately following tuberculin injection.
Local injection of a high-affinity IL-2 receptor antagonist at the site of tuberculin injection.

A patient with a history of recurrent urticaria and angioedema following exposure to unknown triggers undergoes extensive allergy testing. Skin prick tests are negative, and serum IgE levels are within normal limits. However, a basophil activation test (BAT) performed with various allergens reveals significant activation upon exposure to a specific food additive. Which of the following mechanisms BEST explains this discrepancy?

<p>The patient has developed functional autoantibodies against the IgE receptor FcεRI on mast cells and basophils. (C)</p> Signup and view all the answers

In the context of incompatible blood transfusions, an acute hemolytic reaction can occur due to pre-existing antibodies in the recipient that bind to donor red blood cell (RBC) antigens. Apart from direct complement-mediated lysis, which of the following mechanisms contributes MOST significantly to the rapid clearance of antibody-coated donor RBCs?

<p>Phagocytosis by splenic macrophages via Fc receptor-mediated clearance. (D)</p> Signup and view all the answers

Flashcards

What is Hypersensitivity?

An exaggerated immune response to a harmless antigen.

What is Type I Hypersensitivity?

Type I hypersensitivity is triggered by IgE, causing immediate reactions like allergies or asthma.

What are Mediators of Immediate Hypersensitivity?

Mediators like histamine and leukotrienes released during immediate hypersensitivity cause symptoms such as bronchoconstriction and edema.

What is Immunotherapy?

Administration of gradually increasing doses of allergen extracts to induce tolerance.

Signup and view all the flashcards

What is Type II Hypersensitivity?

Type II hypersensitivity is mediated by IgM or IgG, leading to cell lysis or phagocytosis.

Signup and view all the flashcards

Study Notes

Hypersensitivity Overview

Hypersensitivity reactions are classified into four types: Type I, Type II, Type III (immediate reactions), and Type IV (delayed reactions).
The lecture aims to enable students to identify types of hypersensitivity, explain their mechanisms, and describe the clinical types, diagnoses, and treatments.

Type I Hypersensitivity

Type I hypersensitivity is also known as immediate hypersensitivity.
Reactions can manifest in the skin (urticaria and eczema), eyes (conjunctivitis), nasopharynx (rhinorrhea, rhinitis), bronchopulmonary tissues (asthma), and gastrointestinal tract (gastroenteritis).
Common allergens include inhalants like pollen and fungal allergens, injectants like drugs, and contact allergens like antiseptic sprays.
The reaction mechanism involves IgE production in response to allergens.
IgE has a high affinity for receptors on mast cells and basophils.

Mechanism of Type I Hypersensitivity

Subsequent allergen exposure cross-links cell-bound IgE, triggering the release of active substances.
Cross-linking of the IgE Fc-receptor is crucial, leading to mast cell degranulation preceded by increased Ca++ influx.
Preformed mediators in granules include histamine (causing bronchoconstriction, mucus secretion, vasodilation, and vascular permeability), tryptase (proteolysis), and ECF-A (attracting eosinophils and neutrophils).
Newly formed mediators include leukotriene B4 (basophil attractant), leukotriene C4 and D4 (similar to histamine but 1000x more potent), and prostaglandins D2 (edema and pain).

Diagnosis & Treatment of Type I Hypersensitivity

Diagnostic tests involve skin (prick and intradermal) tests, and measurement of total and specific IgE antibodies via ELISA.
Treatment includes avoidance of exposure, symptomatic treatment, and immunotherapy.
Avoidance measures include covering mattresses and pillows with dust mite-resistant covers and removing indoor plants or wet carpets for fungal allergens.
Symptomatic treatments include antihistamines (blocking histamine receptors), chromolyn sodium (inhibiting mast cell degranulation), leukotriene receptor blockers or cyclooxygenase inhibitors (for late-onset symptoms), and bronchodilators (for bronchoconstriction).
Immunotherapy involves administering gradually increasing doses of allergen extracts over years via injection or sublingual drops/tablets to teach the immune system to tolerate the allergen. This leads to stopping the production of IgE and a rise in allergen-specific IgG4 antibodies.

Type II Hypersensitivity

Also known as cytotoxic hypersensitivity, affecting various organs and tissues.
Antigens are typically endogenous, but exogenous chemicals (haptens) attaching to cell membranes can lead to this type.
Mediated primarily by IgM or IgG classes, leading to complement-mediated lysis or phagocytosis and killer cell involvement (ADCC).
Three types of RBC lysis include incompatible blood transfusion, erythroblastosis fetalis, and autoimmune hemolytic disease.
Incompatible blood transfusion includes ABO (intravascular hemolysis with nausea, fever, rigors, and back pain symptoms) and RH (extravascular hemolysis).
Erythroblastosis fetalis happens when an Rh-negative mother gives birth to an Rh-positive infant and subsequently develops antibodies, and in the second birth, the antibodies cross the placenta and cause anemia, jaundice, hepatosplenomegaly, and bilirubin encephalopathy in the infant.
WBC lysis can result in granulocytopenia and is associated with SLE
Platelet destruction is a manifestation of this type.

Type III Hypersensitivity

Type III hypersensitivity involves immune complex hypersensitivity.
Mediated by soluble immune complexes, mainly of the IgG class, though IgM may also be involved.
Antigens can be exogenous (chronic bacterial, viral, or parasitic infections) or endogenous (non-organ-specific autoimmunity, e.g., SLE).

Mechanism of Type III Hypersensitivity

The antigen is soluble and not attached to the organ involved.
Soluble antigen-antibody complexes penetrate the endothelium of blood vessels and deposit on the vascular basement membrane.
This stimulates the complement system, releasing chemotactic factors like C5a, attracting neutrophils that infiltrate, and release lysosomal enzymes, leading to the destruction of the basement membrane.
Type III hypersensitivity includes reactions such as Arthus reaction, serum sickness, hypersensitivity pneumonitis, poststreptococcal glomerulonephritis, and autoimmune diseases like RA and SLE.

Type IV Hypersensitivity

Also known as cell-mediated or delayed-type hypersensitivity.
The classical example is the tuberculin (Mantoux) reaction, peaking 48 hours after antigen injection (PPD or old tuberculin).
Lesions are characterized by induration and erythema.

Mechanism of Type IV Hypersensitivity

CD4+ helper T cells recognize the antigen in a complex with Class II MHC.
Antigen-presenting cells (macrophages) secrete IL-12, stimulating CD4+ Th1 cell proliferation.
CD4+ T cells secrete IL-2 and interferon-gamma, inducing the release of other Th1 cytokines.
Activated CD8+ T cells destroy target cells by direct contact.
Chemokines such as IL-8 and monocyte chemotactic and activating factor (MCAF) lead to macrophage activation, hydrolytic enzyme production, and a maximal local tissue reaction in 48-72 hours.

Clinical Case Scenario

A 74-year-old male accidentally transfused with 500 mL of blood during right hemicolectomy experienced hypotension, acute hemolytic reaction, disseminated intravascular coagulation, and acute kidney injury.
Diagnosis and underlying mechanism should be determined.