Learning outcomes

By the end of this CAL you will be able to:

  • Describe the cellular basis of the four types of hypersensitivity reaction.
  • Describe clinical examples of each.

Introduction Part 1 of 7

Hypersensitivity occurs when the immune system stops being helpful and starts to do damage, and includes allergies.

Hypersensitivity and allergies are increasing:

  • Each year the number of allergy sufferers increases by 5%.
  • 615% increase in hospital admissions for anaphylaxis in 20 years, 1992-2012.
  • Over 20,000 admitted to hospital each year with allergy.
  • £68million per annum is the cost of hospital admissions due to allergy.

There are four types of hypersensitivity.


Type I hypersensitivity Part 2 of 7

  • Type I hypersensitivity includes hayfever, allergic rhinitis, anaphylaxis.
  • It is the classical “allergy”.
  • It is a rapid immune response to an allergen.
  • It is driven by pre-existing IgE to the allergen.

Host response to allergen


©David Dorward, University of Edinburgh 2017 CC BY-SA
Sensitisation in type I hypersensitivity.
  • Exposure of a genetically predisposed individual to an allergen leads to processing by antigen presenting cells such as dendritic cells.
  • Antigen presentation by APCs primes naive T cell bearing specific receptors.
  • After antigen priming, differentiation of naive T cells is skewed towards Th2 cells.
  •  Allergen-primed Th2 cells release cytokines including IL-4 and IL-13; these act on B cells to promote IgE antibody production.
  • IgE is bound by receptors on mast cells for the Fcε part of the antibody.


©David Dorward, University of Edinburgh 2017 CC BY-SA
Re-exposure of sensitised mast cells to allergen.
  • Upon re-exposure, allergen crosslinks FcεR bound IgE on the surface of mast cells.
  • Degranulation releases pre-formed mediators including histamine, serotonin and proteases, leading to immediate symptoms and signs.
  • Synthesis and release of additional mediators including leukotrienes, prostaglandins and cytokines lead to inflammatory cell recruitment (especially eosinophils) producing the late phase response.


  • Proteins, often proteases.
  • A low dose may favour IL-4-producing Th2 responses.
  • Low molecular weight and highly soluble – diffuse into mucus.
  • Very stable – can survive in a desiccated particle.
  • Contain peptides that can bind MHC class II (T cell priming).

Allergens include:

  • Pollens – birch tree, ragweed, oilseed rape.
  • Foods – nuts, eggs, seafood.
  • Drugs – penicillin, aspirin.
  • Insect products – bee venom, house dust mite faecal pellets.
  • Animal products – cat hair, dander (skin and saliva).


  • Profound systemic response to allergens.
  • Vasodilatation due to histamine etc. –
    • Hypotension (low BP).
    • Oedema.
  • Bronchoconstriction (histamine, bradykinins).
  • Treatment is symptomatic –
    • Adrenaline.
    • β-agonists.
    • Intravenous fluids.
    • Corticosteroids.
©Sandy Reid, University of Edinburgh 2017 CC BY-SA


Type II hypersensitivity Part 3 of 7

  • Antibodies formed against an altered component on host cells – IgG or IgM.
  • The host IgG or IgM binds to host cells.
  • Bound antibody accelerates cell clearance by –
    • Phagocytosis.
    • Antibody-dependent cellular cytotoxicity (ADCC).
    • Complement-mediated lysis.
©David Dorward, University of Edinburgh 2017 CC BY-SA
Outcomes of antibody binding to host cells in type II hypersensitivity.
  • Outcomes –
    • Cellular dysfunction.
    • Inflammation.

Example diseases

  • Haemolytic anaemia.
  • Rhesus disease of the newborn.

The Rhesus reaction

This causes haemolytic disease of the newborn – HDNB.

©David Dorward, University of Edinburgh 2017 CC BY-SA
Rhesus disease of the newborn.
  • A RhD- mother, pregnant with a RhD+ foetus, can lead to sensitisation of the mother at birth.
  • Red blood cells from the RhD+ foetus can pass into the maternal circulation. The first baby is unaffected.
  • In the postpartum period, the RhD- mother produces anti-RhD IgG antibodies.
  • In subsequent pregnancies with a RhD+ foetus, the anti-RhD IgG crosses the placenta into the foetal circulation.
  • This leads to haemolysis in the second, and subsequent, pregnancies.
  • Identification of RhD- mothers during their first pregnancy allows intramuscular injection of anti-RhD antibodies at the time birth to destroy any foetal RhD+ red cells before they can elicit an immune response to sensitise the mother.



Type III hypersensitivity Part 4 of 7

  • Immune complex (antigen-antibody) mediated disease.
  • Complexes arise from persistent infection or inhalation and long-term exposure to proteins.
©Karamadoukis et al; licensee BioMed Central Ltd. 2008 CC BY 2.0
Immune-complex deposition in the glomerulus in Henoch-Schonlein nephritis.
©David Dorward, University of Edinburgh 2017 CC BY-SA
Type 3 hypersensitivity.
  • Persistent exogenous or endogenous protein leads to the formation of immune complexes if an appropriate antibody is present.
  • Complexes deposit in tissues with high blood filtration pressure –
    • Kidneys.
    • Joints.
    • Skin.
    • Blood vessels.
  • Immune complexes lead to inflammation and tissue damage; acute inflammation with inflammatory cell recruitment, vasodilatation etc.

Serum sickness

Serum sickness is a transient immune-complex-mediated syndrome caused by the injection of foreign serum proteins.

These lead to the formation of a large number of circulating immune complexes that produce systemic symptoms and signs (fever, vasculitis, arthritis, nephritis).

Host antibody rapidly clears the foreign serum proteins.

Type IV hypersensitivity Part 5 of 7

  • Delayed-type hypersensitivity.
  • T cell-mediated.
  • Response 1-3 days after contact with antigen.
  • Associated conditions –
    • Contact hypersensitivity.
    • Granuloma formation in Tuberculosis (tuberculin test).


Tuberculin reaction

  • Exposure to tubercle bacilli.
  • CD4+ T cell & macrophage accumulation with associated cytokine expression (IFNγ, TNF etc).
  • Epithelioid macrophages surrounded by lymphocytes.
©Sanjay Mukhopadhyay (Syracuse, NY) [Public domain], via Wikimedia Commons
Non-necrotising granuloma in a lymph node in the neck.


Summary Part 6 of 7

Questions Part 7 of 7