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Hypersensitivity Reactions-The Physiological Cause of Allergy

Believe that many of us have been consistently struggling with allergies in our lives. It is a frustrating nuisance that induces an immense range of discomforting feelings, and sometimes even threatens some individuals’ life. However, have you ever wondered how allergies give rise to such responses? The mechanism behind allergy is a group of abnormal physiological responses that can occur within one’s body under certain conditions, collectively named hypersensitivity reactions. In general, hypersensitivity reaction refers to a condition in which the immune system responds exaggeratedly or unnecessarily while exposed to certain antigens, and many of these antigens are usually harmless.

Categorization in General

Hypersensitivity reactions are broadly categorized into 4 types, depending on the type of the response-causing antigen, the type of immune response, and the pace of immune response. Moreover, an additional type of hypersensitivity reaction, referred to as type V, is also proved to exist by some evidence, but many times it is considered a subset of type II hypersensitivity reactions rather than an independent type. (Millar 2023). Within these 4 types, type I, II, and III hypersensitivity reactions are caused by a humoral response (B-lymphocyte activity) while type IV hypersensitivity reactions resulted from the cell-mediated response (T-lymphocyte activity). 

Type I Hypersensitivity Reaction

Also known as an immediate reaction. Under this condition, B-lymphocytes release a particular type of antibody called immunoglobulin E (abbr. IgE) in responding to antigens. This can further trigger the release of histamine and many other chemical compounds that can trigger inflammation. Several food products, external sources that come from animals and other organisms, and some allergic conditions such as allergy rhinitis, can be the factors that can trigger type I hypersensitivity reactions. Some common symptoms of type I hypersensitivity include but are not limited to nausea, vomiting, rash, flushing, and so on.

Type I hypersensitivity involves two stages: the sensitization stage and the effect stage. The sensitization stage refers to the condition in which an individual comes across an antigen for the first time. Interestingly, in this stage, symptoms don’t occur. During the effect stage, the individual is exposed to the antigen the second time. This time, the immune system recognizes the antigen and initiates an immune response.

Type II Hypersensitivity Reaction

Unlike type I hypersensitivity, type II hypersensitivity reaction involves a different category of antibody called IgG. Moreover, it can also involve another class of antibodies called IgM. Type II Hypersensitivity reaction has another name called cytotoxic reaction, because it can lead to the damaging of healthy cells and tissues which can be long-term. As the triggering mechanism and the response can vary regarding this type of hypersensitivity, many subsets were identified, and these subsets often play a key role in the diagnosis of type II hypersensitivity. 

On many occasions, type II hypersensitivity can be caused by an individual taking certain types of medications such as penicillin and thiazides.

There are 3 ways through which cellular damage can be caused. Sometimes, antibodies can bind to receptors residing on the cell surface and cause signaling cascades that can alter cell activities, referred to as type V hypersensitivity mentioned before. Antibodies are also able to activate the complement system of enzymes which can lead to damage. In some occasions, antibodies can “tag” certain cells, attracting some white blood cells to come and attack those cells. This is called “antibody-dependent cellular cytotoxicity”.

Type III Hypersensitivity

This type of hypersensitivity is still caused by humoral response, and it usually involves IgG, IgM, and IgA. Under this condition, antigens and antibodies combine to form immune complexes which build up in organs and tissues such as skin, blood vessels, and so on. These complexes are able to induce the activation of the complement system which attracts inflammatory cells such as monocytes and neutrophils that release enzymes and other substances which can cause cellular and tissue damage.

It can be caused by intaking some type of drugs or certain external sources that come from some other organisms. Moreover, many diseases can be a result of type III hypersensitivity, including but not limited to systemic lupus erythematosus (ELS), serum sickness, and hypersensitivity pneumonitis.

Type IV Hypersensitivity

Type IV hypersensitivity is a cell-mediated form (involves T-lymphocytes) of hypersensitivity, different from the other 3 types, which involves humoral response. Another characteristic that makes type IV hypersensitivity different is that it is delayed. While the other 3 usually occur within 24 hours, which makes them allocated to a group called “immediate hypersensitivity reactions”, type IV typically occurs 12 hours after antigen exposure, and has a reaction time that can reach 48-72 hours.

The exact mechanism of type IV hypersensitivity can involve WBCs in the second line of defense. These WBCs, such as macrophages and monocytes, recognize the antigens present in blood and engulf them. These antigens are presented on their cell surfaces and can further be recognized by T-lymphocytes and cause them to be activated. Once activated, T-lymphocytes will release chemicals such as cytokines and chemokines, which cause damage to cells.

In conclusion, allergic symptoms are primarily caused by hypersensitivity reactions, in which the immune system of an individual is inappropriately and aggressively responding to antigens present in his/her blood that can be either harmful or harmless. Despite that all types of hypersensitivity are caused by abnormal immune responses with respect to the third line of defense primarily, categorization of hypersensitivities is important as the ways of diagnosing, the approach of treatment, and the types of medications used can vary while dealing with each type of hypersensitivity. 


Abbas, Malak, et al. “Type I Hypersensitivity Reaction.” StatPearls, StatPearls Publishing, 17 July 2023.

Bajwa, Shammas F. and Reem H. Mohammed. “Type II Hypersensitivity Reaction.” StatPearls, StatPearls Publishing, 4 July 2023.

Marwa, Khaled. and Noah P. Kondamudi. “Type IV Hypersensitivity Reaction.” StatPearls, StatPearls Publishing, 12 August 2023.

Millar, Hellen. “What Are the Different Types of Hypersensitivity Reactions?”, 14 Oct. 2021,

Usman, Norina, and Pavan Annamaraju. “Type III Hypersensitivity Reaction.” PubMed, StatPearls Publishing, 2020

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