Allergic Diseases and Hypersensitivity Mechanisms

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What is atopy and how does it relate to allergic diseases?

Atopy is a predisposition to respond immunologically to allergens, leading to the differentiation of Th2 cells and increased production of IgE, which contributes to various allergic conditions.

Describe the primary mechanism of Type I hypersensitivity.

Type I hypersensitivity is an immediate allergic reaction mediated by allergen-specific IgE antibodies, which trigger symptoms within minutes after exposure.

What role do mast cells play in allergic reactions?

Mast cells act as primary effector cells in Type I hypersensitivity; they release histamine and other mediators upon encountering allergens.

How does the presence of IgE contribute to allergic responses?

IgE binds to allergens and triggers the activation of mast cells and basophils, leading to the release of histamine and other inflammatory mediators. Signup and view all the answers

What are the potential consequences of severe allergic reactions?

Severe allergic reactions can lead to anaphylaxis, a life-threatening condition that requires immediate medical attention. Signup and view all the answers

What is atopic dermatitis commonly referred to as, and what are its main symptoms?

Atopic dermatitis is commonly referred to as eczema, and its main symptoms include recurrent eczematous lesions and intense itching. Signup and view all the answers

List two genetic or physiological factors contributing to the pathophysiology of atopic dermatitis.

Genetic predisposition and epidermal dysfunction are two contributing factors. Signup and view all the answers

What are the main symptoms of asthma?

The main symptoms of asthma include respiratory distress, chest tightness, wheezing, and coughing. Signup and view all the answers

Distinguish between Type 2 asthma and Non-Type 2 asthma based on their immune components.

Type 2 asthma is driven by Th2 cytokines like IL-4 and involves eosinophils, while Non-Type 2 asthma is driven by IL-8, IL-17, and involves Th17 lymphocytes. Signup and view all the answers

Identify a key outcome of uncontrolled asthma.

A key outcome of uncontrolled asthma is a reduced quality of life. Signup and view all the answers

What role do specific cytokines play in Type 2 asthma?

Cytokines such as IL-4, IL-5, and IL-13 play a significant role in mediating the immune response in Type 2 asthma. Signup and view all the answers

What are some common comorbidities associated with atopic dermatitis?

Common comorbidities include food allergies, asthma, allergic rhinitis, and mental health disorders. Signup and view all the answers

Describe the significance of bronchial hyperresponsiveness in asthma.

Bronchial hyperresponsiveness indicates an exaggerated response of the airways to various stimuli, leading to obstruction and symptoms. Signup and view all the answers

What characterizes an anaphylactic reaction?

An anaphylactic reaction can range from mild to fatal symptoms and is considered a medical emergency. Signup and view all the answers

Name one method for diagnosing type I allergies.

The prick test is one method used for diagnosing type I allergies. Signup and view all the answers

What does the presence of specific IgE indicate?

The presence of specific IgE indicates sensitization to an allergen, though it may not cause symptoms. Signup and view all the answers

How can molecular allergology aid in patient management?

Molecular allergology establishes a precise sensitization profile for patients to guide treatment and allergen immunotherapy. Signup and view all the answers

What role do biologicals play in allergy treatment?

Biologicals are typically prescribed for chronic, severe allergies affecting quality of life, but not for immediate symptoms. Signup and view all the answers

What is allergen immunotherapy (AIT)?

Allergen immunotherapy (AIT) is a treatment approach that involves administering allergen doses to build tolerance. Signup and view all the answers

What are the primary indications for the use of Omalizumab?

Moderate-to-severe persistent allergic asthma, nasal polyps, and chronic spontaneous urticaria. Signup and view all the answers

What is one limitation of the total IgE assay?

The total IgE assay is often less useful than specific IgE assays for diagnosing allergies. Signup and view all the answers

What is the objective of the OUTMATCH trial involving Omalizumab?

To evaluate the effectiveness of Omalizumab in increasing the reaction threshold for food allergens in children with multiple food allergies. Signup and view all the answers

What does the basophil activation test assess?

The basophil activation test measures the response of basophils to allergens to indicate sensitization. Signup and view all the answers

What was the median age of participants in the OUTMATCH trial?

The median age of participants was 7 years. Signup and view all the answers

In the OUTMATCH trial, what percentage of participants receiving Omalizumab met the primary end-point criteria?

67% of participants receiving Omalizumab met the primary end-point criteria. Signup and view all the answers

How important is clinical history in allergy diagnosis?

Clinical history is crucial as it helps correlate sensitivities indicated by IgE tests with actual symptoms. Signup and view all the answers

What are the classic and innovative treatments mentioned in allergy management?

Classic treatments include allergen avoidance and medications, while innovative treatments involve biologicals. Signup and view all the answers

What was the administration frequency of Omalizumab in the OUTMATCH trial?

Omalizumab was administered every 2 to 4 weeks. Signup and view all the answers

Describe the inclusion criteria for participants in the OUTMATCH trial regarding peanut protein.

Participants had to react to ≤ 100 mg of peanut protein during the initial oral challenge. Signup and view all the answers

What are some off-label uses of Omalizumab mentioned in the content?

Off-label use of Omalizumab includes treatment for food allergies and as an adjuvant in immunotherapy for drug and food allergies. Signup and view all the answers

What was the comparative percentage of participants meeting secondary end-point criteria for cashew allergy in the Omalizumab group versus placebo group?

41% in the Omalizumab group compared to 3% in the placebo group. Signup and view all the answers

What is the role of IgE in immediate hypersensitivity reactions?

IgE mediates immediate hypersensitivity reactions by binding to allergens and triggering mast cells and basophils to release histamine and other inflammatory mediators. Signup and view all the answers

Discuss the impact of atopic diseases on daily living and productivity.

Atopic diseases, such as allergic rhinitis and asthma, can significantly impair daily activities, leading to increased healthcare costs and reduced productivity. Signup and view all the answers

What are the immediate clinical symptoms associated with Type I hypersensitivity?

Immediate clinical symptoms include hives, sneezing, difficulty breathing, and in severe cases, anaphylaxis. Signup and view all the answers

What is allergen immunotherapy (AIT) and its purpose?

Allergen immunotherapy (AIT) aims to desensitize patients to specific allergens, reducing their allergic response over time. Signup and view all the answers

Describe the general epidemiology of allergic conditions in Europe based on the 2016 data.

The 2016 epidemiology indicates a high prevalence of allergic conditions in Europe, significantly impacting health and quality of life. Signup and view all the answers

What are potential symptoms of an anaphylactic reaction?

Symptoms can range from mild reactions like hives to severe, life-threatening symptoms including difficulty breathing and loss of consciousness. Signup and view all the answers

How does the quantification of specific IgE contribute to allergy diagnosis?

It helps identify sensitization to specific allergens, guiding clinicians in the management of allergies. Signup and view all the answers

What role does molecular allergology play in allergy management?

It creates individualized sensitization profiles for patients, facilitating targeted treatment approaches. Signup and view all the answers

What are the main therapeutic principles in allergology?

Main principles include allergen avoidance, classical treatments, and allergen-specific therapies like immunotherapy. Signup and view all the answers

What types of allergies might biological therapies be prescribed for?

Biological therapies are typically used for chronic, severe allergies such as atopic dermatitis and certain forms of asthma. Signup and view all the answers

What is the significance of the basophil activation test in allergy diagnosis?

It helps assess the patient's immune response to specific allergens, aiding in the identification of potential triggers. Signup and view all the answers

How do targeted therapies differ from classical allergy treatments?

Targeted therapies focus specifically on individual allergens and their effects, while classical treatments address symptoms non-specifically. Signup and view all the answers

What is the utility of prick testing in allergic conditions?

Prick testing evaluates immediate hypersensitivity reactions to specific allergens, facilitating timely diagnosis. Signup and view all the answers

What is the recommended approach for assessing clinical risk in allergies?

Risk assessment should consider specific IgE levels and patient history related to various molecular allergen families. Signup and view all the answers

What does the presence of specific IgE antibodies reveal about a patient?

It indicates sensitization to particular allergens, which may or may not correspond to clinical symptoms. Signup and view all the answers

What is the primary endpoint achievement percentage for participants receiving Omalizumab in the OUTMATCH trial?

67% Signup and view all the answers

How many food allergies did participants in the OUTMATCH trial have at minimum?

Three food allergies. Signup and view all the answers

What was the duration of Omalizumab treatment in the OUTMATCH trial?

16 to 20 weeks. Signup and view all the answers

Which age group was included in the OUTMATCH trial for Omalizumab treatment?

Children and adolescents aged 1 to 17 years. Signup and view all the answers

What was the increase in reaction threshold for the peanut allergy among participants treated with Omalizumab?

Omalizumab was superior in increasing the reaction threshold. Signup and view all the answers

What role did Omalizumab play in the management of food allergies according to the OUTMATCH trial?

It served as a treatment to increase allergen reaction thresholds. Signup and view all the answers

Can you name one of the key secondary endpoints that showed significant results for Omalizumab in the OUTMATCH trial?

Milk allergy showed 66% vs. 10%. Signup and view all the answers

What was the structure of the random assignment in the OUTMATCH trial?

It was a 2:1 ratio of Omalizumab to placebo. Signup and view all the answers

What two main types of immune mechanisms are involved in atopic dermatitis?

Type-2 immune mechanisms are dominant, but multiple immune pathways are also involved. Signup and view all the answers

Which cytokines are primarily involved in Type 2 asthma?

IL-4, IL-5, and IL-13 are the primary cytokines involved in Type 2 asthma. Signup and view all the answers

List two features that characterize asthma.

Respiratory distress and bronchial hyperresponsiveness are two key features of asthma. Signup and view all the answers

What is the significance of T-cell driven inflammation in the pathophysiology of atopic dermatitis?

It contributes to the chronic nature of the disease and the associated symptoms such as intense itch. Signup and view all the answers

Identify a major risk associated with uncontrolled asthma.

Uncontrolled asthma leads to reduced quality of life. Signup and view all the answers

What skin condition is characterized by recurrent eczematous lesions?

Atopic dermatitis is characterized by recurrent eczematous lesions. Signup and view all the answers

Describe the role of genetic predisposition in atopic dermatitis.

Genetic predisposition influences the likelihood of developing atopic dermatitis. Signup and view all the answers

What is a common comorbidity associated with both atopic dermatitis and asthma?

Food allergy is a common comorbidity associated with both conditions. Signup and view all the answers

Study Notes

Targeted Therapies in Allergogy

Overview of targeted therapies in the field of allergology
Types of hypersensitivity identified:
- Type I hypersensitivity
Diagnostics & testing
- Current methods for allergy diagnosis
- Prerequisite for allergen immunotherapy (AIT)
Therapeutic management techniques
- Classic treatments
- Biological treatments
- Allergen immunotherapy (AIT)

Atopy and Allergy Definitions

Atopy: A predisposition to an exaggerated immune response to various antigens, leading to the production of immunoglobulin E (IgE). Includes conditions like atopic dermatitis, allergic rhinitis, asthma, and food allergies
Allergy: An exaggerated immune response against a harmless foreign substance (allergen) involving an allergen-specific adaptive response.

Burden of Allergic Diseases in Europe

Epidemiology (2016) data:
- 150 million Europeans live with allergies today
- 1 in 2 Europeans will suffer from an allergy by 2025
- Over 20% of Europeans suffer from allergies .
- 100 million experience allergic rhinitis,
- 70 million experience asthma.
- 17 million have food allergies, risk of acute anaphylaxis
- 90% have allergy as a contributing factor to asthma.
- Huge financial burden (€17.7 billion, €9.8 billion, and €55-151 billion/year) due to costs of treatment, lost productivity and indirect costs from untreated allergies.
- Opportunities for savings with proper diagnosis and treatment (€142 billion).

Type I Hypersensitivity

Immediate hypersensitivity response to an antigen
Antigen exposure triggers rapid onset of symptoms
Mediated by allergen-specific IgE antibodies
Involves mast cells and basophils, releasing histamine
Occurs in genetically predisposed individuals ("atopic")
Potential severe life-threatening reactions (anaphylaxis)

Immediate Hypersensitivity (IgE-mediated)

Sensitization phase: First exposure to allergen
- Antigen presentation by dendritic cells to lymphocytes
- Production and release of specific IgE antibodies for this allergen
Elicitation phase (subsequent allergen exposure)
- Immediate elicitation phase: Mast cell degranulation (release of histamine)
- Symptomatic phase: Inflammatory responses
Late elicitation phase:
- Cytokines and chemokines are primarily involved.
  - Neutrophils, Eosinophils, Mast cells, Basophils, other inflammatory mediators involved.
  - Neosynthesized lipid mediators, including prostaglandins, leukotrienes, and platelet-activating factor

Etiological Diagnosis of Type I Allergy

Clinical history and examination
Prick test
Quantification of circulating specific IgE
Basophil activation test

Quantification of Circulating Specific IgE

Total IgE assays are not helpful
Immunochemical methods do exist
The importance of confirming results with clinical history

Molecular Allergology - Component Resolved Diagnosis

Precise and individual sensitization profile for each patient
Document profile according to allergen categories/families
Assess clinical risk (systemic/local reaction risk)
Explain symptoms from cross-reactivity reactions
Indication and guidance, or even performance of AIT

Clinical Risk Assessment

Clinical risk assessment by molecular families :
Categorization of protein types by risk of causing allergic reactions.
Different risk assessment profiles exist

Targeted Therapies in Allergogy (Part 3: Therapeutic Management of Allergies)

Classic Treatments
Biologicals (Monoclonal Antibodies)
Allergen immunotherapy (AIT)

Therapeutic Principles in Allergogy

Allergen avoidance. Includes avoiding exposure to allergens such as domestic pets, food, and certain medications.
Classic treatments. Including non-allergen specific treatments for symptoms.
Innovative treatments. Include treatments not specific to the allergen.
Biological therapies (allergen-specific treatments) .
Allergen immunotherapy (AIT) (allergen-specific treatments) .

Biologicals in the Treatment of Allergies

Typically prescribed for chronic, severe allergies with significant quality-of-life decline.
Not used for immediate symptoms (e.g., acute urticaria, anaphylaxis).
Specific molecular targets: Target soluble mediators, cell surface molecules, and/or alarmins.

Atopic Dermatitis

Chronic, relapsing, inflammatory disorder affecting skin
Typically presents as recurrent eczema, intense itching, and risk of skin infection.
Often associated with other allergic conditions (e.g., food allergy, asthma).
Genetic predisposition and epidermal dysfunction are significant factors.
Primarily T-cell driven inflammation, with type 2 immune mechanisms playing a dominant role.

Asthma

Chronic inflammatory disease of the lower airways characterized by inflammation, obstruction, and hyperresponsiveness.
Respiratory distress, chest tightness, wheezing, coughing, and exercise intolerance.
Bronchial hyperresponsiveness and airway inflammation characterized by mucus plugs and airway remodeling.
Airway wall remodeling occurs. Uncontrolled asthma leads to reduced quality of life.
Different asthma subtypes (Type 2 Asthma, Non-allergic asthma).

Mode of Action of Biologicals Targeting Th2 Immunity

Various biologicals target different aspects of the Th2 immune response to moderate or prevent allergic reactions..

Mechanism of Action of Omalizumab

Binds to free IgE, decreasing cellular IgE
Reduces expression of high-affinity IgE receptors and prevents mediator release.
Decreases eosinophil survival, inducing eosinophil apoptosis
Inhibits allergen presentation to T cells.

Indications of Omalizumab

Moderate-to-severe persistent allergic asthma, Nasal Polyps, Chronic Spontaneous Urticaria
Off-label use in food allergy, as an adjuvant in other treatments for drug and food allergies .

Omalizumab in Food Allergies (OUTMATCH trial)

Trial involving 177 children and adolescents with multiple food allergies.
Omalizumab showed improved oral challenge thresholds for peanuts and other common food allergens, compared to a placebo.

Omalizumab in Food Allergies: Summary of Results

Significantly increase reaction thresholds in participants receiving omalizumab vs. placebo
Data suggests improved reaction thresholds for different allergens, including peanut.

Indications for Four Representative Biologicals (MoAb)

Details on indications of specific monoclonal antibodies for the treatment of allergy conditions.

Immune Mechanisms of TSLP in Asthma

Summary of the role of TSLP (Thymic stromal lymphopoietin), an inflammatory cytokine and its immune interplay with various cells in the context of asthma.

General Tolerance and Side Effects of Biological MoAb

Biologics are generally well tolerated but some side effects may occur, common side effects are local reactions at the injection site, Pseudo-allergic reactions, and general symptoms like headaches, abdominal pain.
Anti-drug antibodies can form and cause therapeutic failure over time.

AIT: Principles and Definitions

Regular administration of allergens to induce allergen tolerance and reduce symptom severity through multiple treatment phases: initial build-up and prolonged maintenance .
Seasonal or Perannual treatments
Different treatment modalities exist.

AIT Indications

Criteria for considering AIT for certain allergy conditions like moderate/severe intermittent allergic rhinitis . Allergic asthma excluding severe or uncontrolled asthma and several other complex conditions.
Allergic manifestations of allergies to hymenoptera, some food allergies (peanut, egg, cow's milk). Atopic dermatitis with pneumallergenic sensitization

AIT Contraindications

Uncontrolled asthma, active autoimmune disease, active neoplasia, cardiovascular pathology, ongoing pregnancy (unless started before), children under 2 years of age are ineligible.

Effects of 2 Years of Grasses Pollen Subcutaneous Immunotherapy (SCIT)

Results on seasonal changes to nasal mucosa from SCIT

Persistence of Allergen-Specific IgG

Persistence of allergen-specific IgG after AIT discontinuation in the long term.

Clinical Efficacy of Grass Pollen Tablets

Summary of study demonstrating clinical efficacy of sublingual immunotherapy (SLIT) for grass pollen allergy in adults, demonstrates significant reduction in nasal and ocular allergy symptoms, and fewer rescue medication requirements.

Clinical Benefits of SLIT in Respiratory Allergy

Details on a five-year sublingual immunotherapy (SLIT) trial for grass pollen allergy , demonstrated positive responses in children with asthma.

Mechanisms of Action of AIT

Summary of the complex mechanisms of action involving multiple cell types and mediators that occur during AIT , involving switching Th2 to Th1, induction of regulatory T cells, increase in IL-10, decrease in release of inflammatory cytokines

AIT: Current Routes of Administration

List of available administration techniques. Includes: subcuntaneous, sublingual,oral

AIT: New Routes of Administration

Summary of new approaches to allergen immunotherapy (AIT), including intranasal and epicutaneous routes, and discussion of potential advantages and challenges.

AIT market in France

Summary market figures (patients on treatment) and prevalent allergen types in France, includes: sublingual, Oral, injection types of therapies .

Source of Allergens for IAT

Sources of allergens for immunotherapy (IAT) .
Method of preparation and standardization for both raw and standardized extracts.

Modified/Recombinant Allergens

Summary of chemically modified or recombinant allergen types (hypallagenic).
Advantages of using modified allergens, including safer administration and potential for improved tolerance, including improvements for safety, efficacy, better treatment, and greater tolerance

Strategies for the Development of a Safer and More Reliable AIT Vaccine

Key strategies for improving the safety and efficacy of AIT treatments, including strategies for developing new and safer methods of allergen delivery, including reduced side-effects, improved adjuvants, new routes of administration

Future ITA Route

Future avenues for IT treatment considering injection and non-injection routes including, intranasal, epicutaneous, sublingual, and oral routes. Includes considerations of modified chemical and recombinant allergens, and the use of TLR-9 agonists, and omalizumab.

Thank You

Thank you for attention.

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Description

This quiz explores key concepts related to atopy, allergic diseases, and the immune response mechanisms involved in Type I hypersensitivity. It covers the roles of mast cells, IgE, and the significance of specific cytokines in asthma and atopic dermatitis. Prepare to test your understanding of the pathophysiology and clinical implications of these allergic conditions.