Hypersensitivity Reactions

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Key points ⚡
Succinct notes to superpower your revision
Immune system\: essential for defence against pathogens; overreaction to exogenous antigens causes allergy, and to
endogenous antigens causes autoimmunity.
Hypersensitivity reactions\: classi
susceptibility or triggering events can lead to hypersensitivity.
Type I hypersensitivity\: immediate reaction mediated by IgE antibodies; leads to allergy, anaphylaxis, atopic disease;
involves mast cell and basophil degranulation releasing histamine.
Clinical relevance\: anaphylaxis\: severe allergic reaction; common allergens include foods, medications, insect stings;
symptoms include airway obstruction, bronchospasm, vasodilation, hypotension; treated with IM adrenaline.
Type II hypersensitivity\: IgG or IgM antibody-mediated cytotoxic reaction; occurs in hours to days; examples include
haemolytic disease of the newborn, autoimmune haemolytic anaemia, Goodpasture’s syndrome.
Clinical relevance\: Goodpasture’s syndrome\: autoimmune condition with antibodies against type IV collagen in alveoli and
glomeruli; presents with haemoptysis, renal dysfunction; treated with steroids, plasmapheresis, cyclophosphamide.
Type III hypersensitivity\: antigen-antibody immune complex-mediated reaction; occurs over hours, days, or weeks;
examples include serum sickness, RA, SLE, post-streptococcal glomerulonephritis; involves immune complex deposition
and in
Type IV hypersensitivity\: delayed hypersensitivity (24-72 hours); T cell-mediated; involved in contact dermatitis and
tuberculin skin test; causes local tissue in
Article 🔍
A comprehensive topic overview

Introduction

The human immune system is vital for defence against pathogens, but at times it can ‘overreact’ causing undesirable
consequences. The e
processes generated via immune cells.
When there is an overreaction to exogenous or ‘non-self’ antigens this can lead to allergy, and with endogenous or ‘self’
antigen this can cause autoimmunity.
By these mechanisms, hypersensitivity reactions are implicated in the pathogenesis of many diseases, and appreciating
the basic cellular processes helps to understand many conditions.
There can be several factors that lead an individual to develop hypersensitivity. There may be a genetic susceptibility to
these reactions or a triggering event of another kind on the immune system such as an infection.
Hypersensitivity reactions have been grouped into four types based on their mechanism, this is known as the Gell and
Coombs classiType I hypersensitivity
Type I hypersensitivity is an immediate reaction (within minutes) mediated by IgE antibody, which results in allergy,
anaphylaxis and atopic disease.
When an individual
this speci
‘sensitised’ to the antigen.
When this antigen is encountered again, it will cause cross-linking of the bound IgE and degranulation of mast cells and
basophils, releasing potent vasoactive molecules such as histamine. This leads to the signs and symptoms of allergy, and
if severe can cause anaphylaxis.
Clinical relevance\: anaphylaxis
Anaphylaxis is a severe allergic reaction occurring rapidly and causing potentially life-threatening issues with an
individual’s airway, breathing or circulation.
Common allergens that can cause anaphylaxis are foods (most commonly nuts), medications, and insect
stings/venom. These allergens trigger a systemic reaction, which via the e
cause swelling and obstruction of the upper airways, bronchospasm and bronchodilation with respiratory failure, and
vasodilation leading to hypotension and cardiac arrest.
Other systemic features may include widespread urticarial rash (‘hives’) and angioedema (swelling).
An allergic reaction causing signs and symptoms of anaphylaxis requires urgent treatment with intramuscular (IM)
adrenaline (0.5mg 1\:1000 in adults) to counteract the vasodilation and bronchoconstriction.
For more information, see the Geeky Medics guide to the acute management of anaphylaxis.

Type II hypersensitivity

Type II hypersensitivity is an IgG or IgM antibody-mediated cytotoxic reaction occurring in hours to days, which results in
pathologies such as haemolytic disease of the newborn, autoimmune haemolytic anaemia and Goodpasture’s syndrome.
An individual may possess or develop IgG and IgM antibodies directed against cell surface or extracellular matrix antigen.
These antibodies can cause damage to cells or tissues (cytotoxicity) either directly by cell surface receptor binding, via
activation of the complement pathway or by antibody-dependent cellular cytotoxicity.
Pathology is dependent on the target of the antibody. If antibodies are directed to cell surface antigen on red blood cells
this can cause haemolytic anaemia, if they are targeted to type IV collagen in the basement membrane this can cause
Goodpasture’s syndrome.
Clinical relevance\: Goodpasture’s syndrome
A classic example of type II hypersensitivity is Goodpasture’s syndrome, a rare autoimmune condition caused by
antibodies against the alpha-3 chain of type IV collagen found in the basement membrane.
Type IV collagen is a major structural component of all basement membranes, but the alpha-3 subtype only occurs in
certain tissues, primarily alveoli and glomeruli. There is no consistent trigger for the disease, but it is associated with
certain genetics (HLA-DRB1 or DR4) and cigarette smokers.
The condition commonly presents in men, with bimodal age distribution (20 to 30 years and 60 to 70 years).
Symptoms include shortness of breath, haemoptysis and signs of renal dysfunction such as decreased urine output
or oedema. Goodpasture’s can lead to rapidly progressive renal failure if untreated.
Diagnosis is made by renal biopsy and can be con
GBM antibodies) and cyclophosphamide. Patients may require long-term dialysis if irreversible renal damage occurs.

Type III hypersensitivity

Type III hypersensitivity is an antigen-antibody immune complex-mediated reaction, which can occur over hours, days or
weeks. Examples include serum sickness, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and post-
streptococcal glomerulonephritis.
Soluble antigen in the circulation is bound to by antibodies (most commonly IgG and IgM) forming immune complexes.
These complexes can precipitate out of the circulation and deposit in certain tissues, notably blood vessels, synovial joints
and the glomerular basement membrane.
These complexes trigger the classical complement pathway, leading to the recruitment of in
neutrophils that release enzymes and free radicals causing tissue damage. These in
pathology in diseases such as rheumatoid arthritis, where immune complexes damage the
synovial

Type IV hypersensitivity

Type IV hypersensitivity is also known as delayed hypersensitivity, as the reaction typically occurs 24 to 72 hours after
antigen exposure. Unlike types I to III, it is not antibody-mediated but T cell-mediated. It is involved in the processes of
contact dermatitis and the tuberculin skin test (Mantoux).
When an individual
T helper cells.
On subsequent exposure to this antigen, these T helper cells will become activated and lead to an in
involving several immune cells such as macrophages, though there will be a delay of 24 to 72 hours as cells are recruited
to the site of antigen exposure.
This can cause local tissue in
poison ivy contact the skin, or in the Mantoux test where proteins from M . t u b e r c u l o s i s are injected intradermally and an
indurated area forms in individuals who have been previously exposed to the bacteria.

Summary

The four types of hypersensitivity reactions, as per the Gell and Coombs classi
Table 1. The key features of the four types of hypersensitivity reaction.
Type Mediated by Timeframe Examples
Type I
hypersensitivity
IgE antibody
Immediate
(minutes)
Allergy, anaphylaxis, atopy
Type II
hypersensitivity
IgG or IgM
antibody
(cytotoxic)
Hours to days
Haemolytic disease of the
newborn, autoimmune
haemolytic anaemia,
Goodpasture’s syndrome
Type III
hypersensitivity
Type IV
hypersensitivity
Antigen-
antibody
immune
complexes
T cells
Hours to
days/weeks
Serum sickness, RA, SLE,
post-streptococcal
glomerulonephritis
Delayed (24 to 72
hours)
Contact dermatitis,
tuberculin skin testReferences
Justiz Vaillant AA et al. I m m e d i a t e H y p e r s e n s i t i v i t y R e a c t i o n s | S t a t P e a r l s . Published 2021. Available from\: [LINK]
Dispenza MC. C l a s s i LINK]

Reviewer

Dr Dinusha Chandratilleke
Consultant Immunologist

Related notes

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Contents

Introduction
Type I hypersensitivity
Type II hypersensitivity
Type III hypersensitivity
Type IV hypersensitivity
Source\: geekymedics.com