Hypersensitivity and Allergy

What is hypersensitivity defined as?

A state of altered reactivity in which the body reacts with an exaggerated immune response to a foreign agent.

What type of reaction is Type 1 hypersensitivity, and give an example.

IgE mediated, eg. Atrophy, anaphylaxis.

What type of reaction is Type 2 hypersensitivity, and give an example.

Non-IgE mediated (cytotoxic) eg. Haemolytic anaemia.

What type of reaction is Type 3 hypersensitivity, and give an example.

Non-IgE mediated (immune complex) eg. Serum sickness.

What type of reaction is Type 4 hypersensitivity, and give an example.

Non-IgE mediated (cell mediated) eg. Sarcoidosis, TB, Crohn’s disease.

Which type is the most common hypersensitivity reaction?

Type 1 (IgE mediated/immediate hypersensitivity).

What are the consequences of a type 1 hypersensitivity reaction?

From mild irritation-life threatening (eg. Anaphylaxis).

Caused by the release of inflammatory mediators (eg. Histamine) from mast cells and basophils.

Describe the role of IgE in Type I hypersensitivity reactions.

IgE producing B cells activated during first exposure. IgE binds to Fc receptor on mast cells or CD63 on basophils. IgE recognises allergen and next exposure binds rapidly and causes immediate degranulation.

Give examples of allergens that can cause eczema (type I hypersensitivity reaction).

Soaps and detergents, dust mites, fur, pollen, bacterial and fungal antigens.

Describe the steps of system anaphylaxis.

Antigen in bloodstream enters tissues and activates connective tissue mast cells throughout the body. Mast cell degranulation occurs and there is a mass release of inflammatory mediators. This causes swelling of tissues including tongue, loss of blood pressure, reduced oxygen to tissues, irregular heartbeat, contraction of smooth muscle and constriction of airways, dyspnoea, stomach cramps, vomiting, fluid outflow into gut.

How does penicillin cause anaphylaxis in some individuals?

Penicillin contains a B-lactam ring, that is highly reactive and can react with amino groups on proteins- therefore, it attaches to carrier proteins and is termed a hapten. In some individuals, penicillin-peptide complexes initiate an IgE response.

Describe how a skin prick test would be carried out to determine a type 1 hypersensitivity reaction.

Skin is pricked with tiny amount of suspected allergen, results in about 20 minutes. Skin around prick becomes itchy and red, and a wheal will appeal if allergic.

How would a blood test determine a type I hypersensitivity reaction?

Blood IgE antibody levels measured in response to allergen.

When would a patch test be done to determine type I hypersensitivity reaction?

To test if skin reaction is due to contact with specific allergen.

Name 4 drugs that can be used as treatments for a type I hypersensitivity reaction.

Antihistamines, hydrocortisone, cromoglycate, epinephrine.

How do antihistamines work in the treatment of type I hypersensitivity reaction?

They compete with histamines for receptors.

How does hydrocortisone work in the treatment of a type I hypersensitivity reaction?

It blocks histamine synthesis.

How does cromoglycate work in the treatment of a type I hypersensitivity reaction?

It stabilises mast cells and stops histamine release.

How does epinephrine work in the treatment of a type I hypersensitivity reaction?

It stimulates adrenoreceptors. This increases peripheral and vascular resistance, improves blood pressure and coronary perfusion, decreases angioedema, causes bronchodilation and increases intracellular cAMP in mast cells and reduces release of inflammatory mediators.

What is a biphasic response (anaphylaxis)?

When there is a recurrence of anaphylaxis several hours after resolution of the initial symptoms. Occurs in 4-20% of cases, so observe patient for up to 12 hours after apparent recovery from initial episode.

What happens during a type II hypersensitivity reaction?

IgG or IgM binds to an antigenic cell. Cell is lysed by membrane attack complex formation and antibody dependent cell mediated cytotoxicity.

Give an example of type II hypersensitivity reaction.

Haemolytic anaemia.

Explain how a type III hypersensitivity reaction works.

Involves reactions against soluble antigens circulating in serum. There are antibody-antigen aggregates in tissues. Immune complexes can activate complement and active macrophages. This leads to inflammatory response leading to tissue injury.

Describe what occurs in the body during Arthus Reaction.

There is an intradermal injection of antigen. Antigen-antibody complexes are deposited in localised tissues and there is a localised vasculitis response. Then PNS complement activation and mast cell sensitisation occur. This activates phagocytes and localised inflammatory response, which can cause blood vessel occlusion due to accumulation of platelets.

Describe what happens in the body during serum sickness.

It is a systemic Arthus reaction due to large quantities of injected antigen. Antibody-antigen complexes circulate and lodge in many different tissues. Mechanism of damage is the same as Arthus reaction but more widespread.

What are the symptoms of serum sickness?

Vasculitis, rash, fever, joint swelling/pain.

Characteristic symptom of oral erythema muliforme?

Crusty blistering of oral mucosa.

Describe the mechanism of action of Oral Erythema Multiforme.

Caused by deposition of immune complexes (IgM) in the microvasculature of the oral mucous membrane. Can be caused by hypersensitivity to drug/protein complexes.

Name a drug that can cause oral erythema multiforme.

Trimethoprim-sulfamethoxazole (TMP/SMX or cotrimoxazole).

Name examples of type IV hypersensitivity reactions.

Type I diabetes, rheumatoid arthritis, multiple sclerosis, Crohn’s disease, psoriasis.

What occurs in the body during a type IV hypersensitivity reaction?

There is a localised T cell response to foreign proteins or modified cell proteins. Can involve both CD4+ (inflammation induced damage) and CD8+ (direct damage of cells).