Allergy Mechanisms and Type I Hypersensitivity

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Questions and Answers

What is the primary mechanism behind a Type I hypersensitivity reaction?

Cytotoxic T-cell activation

IgG mediated complement activation

Immune complex deposition in tissues

IgE mediated mast cell degranulation (correct)

Which type of hypersensitivity reaction is uniquely mediated by T-cells, rather than antibodies?

Type I

Type III

Type II

Type IV (correct)

What is the role of TH2 cells in the context of an allergic reaction?

Secreting interleukins, promoting IgE production, and mediating the humoral immune response (correct)

Activating cytotoxic T-cells

Suppressing the immune response

Directly killing infected cells

What distinguishes an allergen from other antigens?

They are antigens that cause an abnormal immune response. Signup and view all the answers

Which of these best defines the term 'Atopy'?

A predisposition for an IgE-mediated response Signup and view all the answers

In the case of a wasp sting reaction, what is the primary reason for the observed oedema?

Mast cell degranulation and histamine release causing vasodilation and increased permeability Signup and view all the answers

What is the mechanism of action of Chlorpheniramine?

H1 histamine antagonist Signup and view all the answers

What is the aim of the hypersensitisation immunotherapy?

Decrease or eliminate the body’s immune response to a specific allergen Signup and view all the answers

Which cytokine is primarily responsible for the differentiation of naive T-helper cells into TH2 cells during an allergic reaction?

IL-4 Signup and view all the answers

What is the primary role of IL-5 in the context of an allergic response?

Activating and recruiting eosinophils Signup and view all the answers

Which of the following best describes the function of the FcεR1 receptor?

It binds to the constant region of IgE antibodies on mast cells and basophils. Signup and view all the answers

During degranulation, which preformed mediator activates the complement system?

Tryptase and chymase Signup and view all the answers

Which newly synthesized mediator is most potent at causing smooth muscle contraction of the airways in an allergic reaction?

Leukotrienes C4 and D4 Signup and view all the answers

What direct effect does histamine have on blood vessels during an allergic response?

Vasodilation Signup and view all the answers

Which of these occurs first in an immediate hypersensitivity reaction, after initial exposure to the allergen?

Class switching of B cells to produce IgE antibodies. Signup and view all the answers

Which of the following is NOT a function of histamine during an allergic reaction?

Vasoconstriction. Signup and view all the answers

What is the primary mechanism by which leukotrienes and cytokines contribute to the late-phase allergic response?

Migration of leukocytes, particularly eosinophils, to the site of inflammation. Signup and view all the answers

Which of the following best describes the action of H1 antihistamines in reducing hypotension and oedema?

By preventing vasodilation and reducing the effects of increased vascular permeability. Signup and view all the answers

A patient with rhinitis and urticaria is prescribed a second-generation antihistamine. Which of the following drugs would be most appropriate?

Fexofenadine Signup and view all the answers

What is the primary pharmacological effect of H2 antihistamines?

Reducing gastric acid production in the stomach. Signup and view all the answers

Which of the following explains why first-generation H1 antihistamines are more likely to cause sedation?

They have a greater central effect and cross the blood brain barrier. Signup and view all the answers

A patient experiencing motion sickness is seeking medication. Which of the following would be the most appropriate first-generation H1 antihistamine?

Promethazine Signup and view all the answers

How do H1 antihistamines alleviate the sensation of pruritus (itching)?

By competing with histamine for H1 receptors on peripheral nociceptors. Signup and view all the answers

What aspect of glucocorticoids makes them useful in treating inflammation?

Their anti-inflammatory properties. Signup and view all the answers

What is the primary function of negative selection in T cell development within the thymus?

To induce apoptosis or suppress T cells that bind with high affinity to self-peptides. Signup and view all the answers

Which of the following best describes the nature of autoantibodies?

Antibodies that react with self-antigens found in the body. Signup and view all the answers

Which of the following is NOT a commonly identified composition of autoantibodies?

Minerals Signup and view all the answers

What is the typical antibody isotype associated with autoantibodies in most diseases?

IgM Signup and view all the answers

Which of these is LEAST likely to result in an autoimmune issue?

Exposure to a toxic chemical Signup and view all the answers

In the context of autoimmunity, what does the concept of 'molecular mimicry' refer to?

Infectious agents with amino acid sequences or structures similar to host self-antigens, causing cross-reactivity. Signup and view all the answers

How do 'cryptic antigens' contribute to autoimmunity?

By becoming accessible to self-reacting T cells due to tissue damage or changes. Signup and view all the answers

What role do T regulatory cells play in preventing autoimmunity?

They suppress the activity of other T cells, thereby limiting tissue damage. Signup and view all the answers

What is the primary mechanism by which glucocorticoids exert their anti-inflammatory and immunosuppressive actions?

Binding to glucocorticoid receptors, leading to changes in gene transcription. Signup and view all the answers

Which of the following is a short-term effect of glucocorticoid administration?

Decreased vasodilation and decreased capillary permeability. Signup and view all the answers

What is a long-term effect of glucocorticoid use, caused by the binding of the glucocorticoids to cytoplasmic receptors?

Promotion of apoptosis in eosinophils, monocytes and lymphocytes Signup and view all the answers

Which of the following is a consequence of glucocorticoids' inhibition of phospholipase A2?

Decreased production of arachidonic acid derivatives Signup and view all the answers

Besides anti-inflammatory and immunosuppressive actions, which other effects are commonly associated with glucocorticoids?

Reduced sodium excretion and increased potassium excretion. Signup and view all the answers

What is the effect of glucocorticoids on cell apoptosis and fibroblast proliferation?

Stimulate cell apoptosis and inhibit fibroblast proliferation. Signup and view all the answers

In the context of steroid abuse, which effect can be associated with glucocorticoids?

Increased muscle mass and strength. Signup and view all the answers

What is the primary characteristic of superantigens?

They activate a large number of T lymphocytes regardless of their antigen specificity. Signup and view all the answers

Which of these drugs is an example of a locally administered glucocorticoid?

Beclomethasone Signup and view all the answers

What is meant by ‘bystander action’ in the context of autoimmune diseases?

The enhanced presentation of self-antigens leading to an expansion of the immune response towards other self-antigens. Signup and view all the answers

Which of the following factors is NOT typically implicated in the development of autoimmune diseases?

A prolonged period of good health. Signup and view all the answers

Organ-specific autoimmune diseases like Graves’ disease are often easier to diagnose because:

They frequently present with symptoms directly related to the affected organ. Signup and view all the answers

What is a key characteristic of systemic autoimmune diseases?

They can affect multiple organs or systems in the body. Signup and view all the answers

Which symptom is LEAST likely to be associated with autoimmune disorders?

Persistent and specific organ pain. Signup and view all the answers

Why can diagnosing autoimmune disorders be difficult?

People may have multiple autoantibodies and autoimmune disorders and a lack of detectable autoantibodies. Signup and view all the answers

What are the potential complications that can arise from systemic autoimmune diseases?

Vasculitis and anaemia. Signup and view all the answers

Study Notes

Abena Naylor Case Study

A 31-year-old female experienced periorbital and lip edema after a wasp sting.
Her blood pressure and heart rate were elevated.
After receiving intramuscular (IM) drugs, her blood pressure returned to normal, but the edema persisted.
She was concerned that this episode might lead to rheumatoid arthritis.

Terms and Definitions

Periorbital: Edema around the eyes.
Chlorpheniramine: A histamine reverse agonist (H1).
Hydrocortisone: A glucocorticoid nuclear receptor agonist.
Epipen: An auto-injector containing adrenaline.
Hypersensitisation: Allergen immunotherapy aimed at diminishing the body's immune response to an allergen.

Hyper-sensitivity

An abnormal immune response causing potential harm to the body.
It occurs only in sensitized individuals.
Categorized into four types:
- Type I: Immediate allergic reactions (e.g., food, asthma, anaphylaxis).
- Type II: Cytotoxic reactions involving antibodies targeting specific tissues (e.g., autoimmune hemolytic anemia).
- Type III: Immune complex-mediated reactions causing tissue damage.
- Type IV: Delayed reactions mediated by T-cells (e.g., delayed hypersensitivity).
Causes include infections and environmental/self-antigens.

Allergen in Wasp Bite

Allergen: Substance triggering an immune response.
Often small proteins (containing protease).
Usually mediates TH2 immune response.
TH2 cells: A sub-type of T-cells involved in immune responses to extracellular parasites and bacterial infections.
TH2 response characterized by eosinophils, basophils, and mast cell degranulation (release of inflammatory chemicals).

Sensitization

The body's initial exposure and response to an allergen.
Antigens bind to receptors on antigen-presenting cells (APCs).
Antigens are presented to T-helper cells (TH cells), activating a TH2 response.
TH2 cells release cytokines, including IL4, IL5, and IL13.
IL4, promotes further TH2 cell activation.
IL5, recruits eosinophils.
IL13 promotes IgE production and epithelial cell stimulation.
IgE is produced and binds to mast cells/basophils, preparing for re-exposure.

Re-exposure - Immediate Reaction

Within 5-30 minutes of re-exposure.
Allergen cross-links IgE on mast cells/basophils.
Degranulation releases preformed mediators (e.g., histamine) and newly synthesized mediators (e.g., cytokines, leukotrienes).
Symptoms include smooth muscle contraction, vasodilation, increased vascular permeability, and itch (pruritus).

Re-exposure - Late Reaction

2-24 hours after re-exposure.
Involves leukocytes (especially eosinophils)
Release of substances causing tissue damage.

Allergic Reactions Treatments

Antihistamines (H1/H2):
- H1: First and second generations, primarily used as anti-allergy drugs (e.g., chlorpheniramine, and fexofenadine).
- H2: Treat gastric reflux by reducing acid production (e.g., ranitidine, cimetidine).
Glucocorticoids:
- Anti-inflammatory and immunosuppressive effects.
- Immediate and long-term effects to reduce inflammation.

Anaphylactic Reaction

Assess: Airway, breathing, circulation, disability, exposure.
Diagnosis: Look for acute onset, skin changes, and exposure to allergen.
Call for help: Lie patient flat, raise legs if breathing is impaired.
When skills and equipment are available: Establish airway, high-flow oxygen, IV fluid challenge, monitor pulse oximetry, ECG, blood pressure.
Treatment: Adrenaline, chlorphenamine, hydrocortisone

Self-Antigens

Immune system develops mechanisms to avoid reacting against the body's own components.
T-cells (thymocytes) mature in the thymus.
Those with receptors for self-antigens are deactivated to prevent autoimmune responses.

Autoantibodies

Antibodies that react with self-antigens.
Can cause damage to healthy cells.
Mechanisms include molecular mimicry, protein changes, cryptic antigens, super-antigens.

Autoimmune Diseases

Disorders where the immune system attacks the body's own tissues or cells.
Can be organ-specific (affecting a single organ, such as the thyroid) or systemic (affecting multiple organs).
Signs/symptoms: often non-specific (e.g., fatigue, fever, rashes).
Difficult to identify the cause.

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Description

This quiz explores the principles of Type I hypersensitivity reactions, the role of various immune cells, and mechanisms involved in allergic responses. Test your understanding of allergens, cytokines, and treatment options related to atopic reactions.