What is Hypersensitivity?

By Chandan Sekhon - Medicine Student @ Peterhouse, Cambridge

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Hypersensitivity describes immune responses that are generated when the immune system overreacts to stimuli. These responses are often damaging to the host.

Type I Hypersensitivity:

This type of hypersensitivity is the immune response to contact with an antigen which the organism has pre-existing IgE (immunoglobulin E) antibody for, which has been generated in response to allergens. Initially, mast cells become activated through specific receptors as antigen molecules bind to IgE molecules. This response is rapid, lasting a few hours. This rapid response is due to mast cells releasing histamine. A few hours later, secondary inflammatory mediators are released during the late response. This class includes allergic reactions, such as hay fever and asthma. Many allergens could trigger this response, including shellfish and penicillin. This only affects a certain subset of individuals, as these allergens wouldn’t normally induce an immune response. This suggests there could be a genetic component.

Type II Hypersensitivity:

This is an immune response arising from IgM and IgG antibodies binding to tissue antigens. This triggers clearance by macrophages located in the spleen which have specific receptors on their cell surface membranes. One of the most common forms of this class is blood transfusion. The ABO blood group system is the reason for this. Individuals may be one of four blood types, A, B, AB or O. The table below describes these groups:

	Group A	Group B	Group O	Group AB
Antigens present	A antigen	B antigen	No antigen	A and B antigens
Antibodies present	Anti-B	Anti-A	Anti-A and anti-B	None

Type III Hypersensitivity:

This response occurs when the soluble antigen is present in high quantities (as IgE responses tend to take place in cases where low quantities are present). Immune complexes form, which are then transported to tissues. In tissues, mast cells are triggered due to specific low-affinity receptors and inflammation can result. As well as this, local tissue damage often takes place as a result of the immune response. An example of this reaction is the Arthus reaction which can be triggered in the skin of certain individuals who contain IgG molecules against the sensitising agent.

Type IV Hypersensitivity:

This type is called delayed-type hypersensitivity as the effect is maximal in around 2 days, and unlike the other types of hypersensitivity, it is mediated by specific T cells which release cytokines. In turn, these recruit mononuclear cells. A key example of type IV hypersensitivity is tuberculosis. Compared with antibody-mediated hypersensitivity, significantly more antibody is required for type IV reactions. Macrophages that have been recruited to the site of inflammation by chemokines present antigens to T cells and amplify the response.

Treatment:

Treating immediate hypersensitivity reactions involved managing anaphylaxis with hormones or intravenous support. For example, asthma (a type I reaction) can be treated with bronchodilators, corticosteroids etc. This contrasts with delayed hypersensitivity reactions (type IV reactions), which involved treating the cause of the response. Anti-TNF monoclonal antibodies can be used for the treatment of Crohn disease, for example.

To conclude, there are four types of hypersensitivity reactions which all differ in mechanism of action, and also in length of action. Types I-III are similar to each other in that they are antibody-mediated, and all have similar methods of management. Type IV reactions are T-cell mediated (specifically TH1 cells) and thus have longer courses of action and different methods of treatment.

Further reading:

1. This is an interesting article looking at hypersensitivity reactions in the specific case of IBS (irritable bowel syndrome). A pretty intensive read but interesting: https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2982.2006.00875.x

2. A book chapter outlining the four types of hypersensitivity. A short read and gives a good summary of everything in this article: http://www.hob-biotech.com/upload/201911/26/201911261011022271.pdf

3. A revision website which gives a good outline of the types of hypersensitivity: https://pathologia.ed.ac.uk/topic/hypersensitivity/

4. This article describes hypersensitivity reactions in the context of drugs – reactions people may have to medications: https://www.karger.com/Article/Fulltext/458725