L9 - Diagnostics and Therapy of Allergy

1 in ____ people experience allergies and asthma

5

3 multiple choice options

What is allergy?

An unwanted exaggerated immune reaction to innocuous environmental antigens also known as allergens

What is another term to describe allergy?

Atopy

What are four routes of exposure to allergens?

Inhaled materials, injected materials, ingested materials, and contacted materials

What is the most common type of allergen?

House dust mite feces (inhaled)

What is sensitization?

The first exposure to an allergen that is required for an allergic response to occur in subsequent exposure

Describe the process of sensitization in Class I hypersensitivity

The allergen enters the body and is degraded by APCs. APCs present the antigen to naive T cells on MHC molecules which then activate the T cell. The T cell activates B cells which produce IgE antibodies. IgE antibodies bind to mast cells

Upon re-exposure to an antigen, there can be two responses, the early and late phase response. Describe the early phase

Allergens bind to the IgE antibodies (crosslink) that were made in sensitization which causes mast cells to degranulate.

What is Peak Expiratory Flow Rate (PEFR)?

A measurement of how quickly a person can exhale air from their lungs after taking a deep breath. Often used in those with asthma

How is PEFR affected by an antigenic challenge?

It reduces substantially, often to a point of fatality.

What accounts for the immediate phase in PEFR after an antigenic challenge?

The early-phase mediators that are produced from mast cell degranulation, such as histamine, heparin, TNF-alpha, etc.

The immediate phase response is associated with which class of hypersensitivity?

Class I

What accounts for the lag phase in PEFR after an antigenic challenge?

The lag-phase mediators that are produced from mast cell degranulation such as prostaglandins, leukotrienes, etc. Can also be due to delayed hypersensitivity (IV)

The lag phase response is associated with which class of hypersensitivity?

Class I (and IV)

Upon re-exposure to an antigen, there can be two responses, the early and late phase response. Describe the late phase

Occurs from the activity of T cells which have a delayed reaction compared to antibodies that have the immediate reaction.

The late phase response is associated with which class of hypersensitivity?

Class IV

Class IV hypersensitivity is _____-mediated

cell (NO antibodies)

What is the role of TH1 cells in Class IV hypersensitivity?

Mediated atopic dermatitis, produce cytokines and chemokines, and aid in producing allergic rhinitis/asthma

What is the role of TH2 cells in Class IV hypersensitivity?

Activate eosinophils, basophils, mast cells, etc.

What are the roles of eosinophils, basophils, and mast cells in Class IV hypersensitivity?

Degranulate to produce histamine, lipid mediators, cytokines, chemokines, etc.

What is the role of Memory B cells in Class IV hypersensitivity?

Produce IgE

What are the goals of diagnosing allergies?

To establish that the disease is allergy and to determine specific allergens

Give four steps involved in diagnosis of an allergy

Comprehensive history, physical examination, non-immunological tests, and immunological tests

Give three types of immunological diagnostic tests

Allergy skin tests, in vitro tests for IgE, and provocative/elimination tests

What is an allergy skin test?

A procedure used to identify allergic reactions by exposing the skin to small amounts of allergens and checking for a reaction

Is immediate or late-phase hypersensitivity determined in allergy skin tests?

Both

2 multiple choice options

Name two types of allergy skin tests for immediate hypersensitivity

Cutaneous and intradermal

Cutaneous allergy skin tests for immediate hypersensitivity

Allergenic extract is injected via cutaneous routes. A positive test is a wheal or flare

Intradermal allergy skin tests for immediate hypersensitivity

Allergenic extract is injected intradermally and is effective for all allergies but food/drugs

Name one type of allergy skin test for delayed hypersensitivity

Patch tests

Patch tests for delayed hypersensitivity

Small amounts of allergens are placed on a patch, which is then applied to the skin. Used to identify contact allergens that trigger a T-cell-mediated immune response.

When does a delayed hypersensitivity allergic reaction present? What are some symptoms?

In 24-48 hours. Usually seen with erythema and redness

Give some examples of patch tests

Tuberculin for a TB test or Mantoux test, Spherusol for Coccidoiodomycosis, Candin for Candida albicans, etc.

What medications should not be used during allergy skin tests?

Antihistamines and oral corticosteroids

Why should antihistamines and oral corticosteroids not be used during an allergic skin test?

It could give a false negative by suppressing the immune response

What is an in vitro test?

A laboratory blood test used to detect allergen-specific antibodies (IgE) in the blood, helping diagnose allergies without exposing the person to allergens directly

Give three examples of in vitro testing for allergies

RAST (radioallergosorbent)

MAST (multiple allergosorbent, ELISA)

FAST (fluorescent allergosorbent)

Give the principle behind in vitro allergy tests

Allergens are attached to a solid phase and the patient's serum is added. If specific IgE is present, it binds to the allergen. A specifically labeled anti-IgE antibody is then added, which binds to the captured IgE. The labeled IgE level is measured, indicating the amount of allergen-specific IgE

What is the specific label on IgE for RAST? MAST? FAST?

Radioactive products; enzyme-linked immunoassay; fluorescence

What is provocative testing for allergies?

A suspected allergen is directly introduced into the body to observe if it triggers an allergic reaction. Doses are gradually increased

What are some target tissues for provocative allergy tests?

Respiratory, GI, or cutaneous tissues

Why are provocative tests performed in a clinical setting?

Due to the risk of severe reactions. Emergency treatments (e.g., epinephrine, antihistamines) are readily available

What is elimination testing for allergies?

When the suspected allergen is removed from the persons lifestyle to see if it brings any relief (e.g. new skincare)

Name some common therapies used to treat allergies (mainly IgE mediated allergies)

Minimize exposure to antigen, symptomatic therapy, and immunotherapy (desensitization/hyposensitization)

When is immunotherapy normally recommended?

With worsening conditions not relieved by eliminating the allergen or symptomatic therapy

Describe immunotherapy (sensitization)

A long-term treatment that reduces allergic responses by gradually exposing the immune system to increasing doses of an allergen. This helps the body develop tolerance and decrease hypersensitivity over time

What are the three methods or ROAs of immunotherapy?

Subcutaneous, sublingual, and oral

Subcutaneous immunotherapy

Desensitizes the immune system to specific allergens through regular subcutaneous injections. Used for conditions like asthma, rhinitis, and insect hypersensitivity

Give some examples of FDA approved sublingual immunotherapy

Oralair, Grastek, Ragwitek, and Odactra

Oralair and Grastek

Used to treat mixed grass pollen-induced allergic rhinitis

Ragwitek

Used to treat short ragweed pollen-induced allergic rhinitis

Odactra

Used to treat allergies induced by house dust mites

Give an example of an FDA approved oral immunotherapy

Palforzia for peanut-induced allergy

What is the main cell produced in a successful immunotherapy that aids in decreasing hypersensitivity?

Allergen specific Treg cells

Give some characteristics of successful immunotherapy

Class switching from IgE to IgG, TH1 instead of TH2, and production of anti-inflammatory cytokines (IL-10/TGF-beta)

Name some suppression actions of Treg cells in successful immunotherapy

Suppression of granulocytes, TH2 cells and effector T cells, tissue inflammation, mucus production, inflammatory DCs, and IgE production

What is the first event seen in successful immunotherapy?

Decrease in mast cell and basophil (granulocyte) degranulation

What is the second event seen in successful immunotherapy?

Generation of allergen specific Treg cells and suppression of effector T cells

What is the third event seen in successful immunotherapy?

Early increase in IgE and then a late decrease in IgE

What is the fourth event seen in successful immunotherapy?

Increase in IgG4

What is the fifth event seen in successful immunotherapy?

Decrease in type I skin test reactivity

What is the sixth event seen in successful immunotherapy?

Decrease in tissue mast cell and eosinophil and release of mediators

Describe general characteristics of allergenic extracts

Mainly composed of aqueous solutions and are crude pharmaceuticals. There are non-standardized and standardized

Non-standardized allergenic extracts

Natural allergen extracts used in allergy testing and immunotherapy but lack consistent potency, concentration, and allergen composition. Do not have a standardized unit of allergen content

There are _____ licensed manufactures for non-standardized extracts

6

Standardized allergenic extracts

Allergen preparations with consistent potency, composition, and biological activity, ensuring reproducible results in allergy diagnosis and immunotherapy. Regulated by agencies like the FDA to maintain uniformity and effectiveness.

There are ______ standardized allergenic extracts

19