The human immune system creates a strong shield of defence against pathogens. However, at times, it may ‘overreact’, resulting in undesirable outcomes. These effects on someone’s body are not generated by antigens but by several inflammatory mechanisms in which the immune cells are directly involved. 

These mechanisms cause hypersensitivity reactions, which can lead to different diseases. In many cases, pathologists find a genetic susceptibility to these reactions or a triggering event like an infection can be the root cause of the problem. 

In this guide, you will learn in detail about the four types of hypersensitivity reactions, popularly termed the Gell and Coombs classification. Additionally, we will explain the various causes of hypersensitivity, their mechanisms and more. 

What are Hypersensitivity Reactions?

Hypersensitivity reactions sum up excessive or abnormal responses of a human body’s immune system to different foreign substances or allergens. 

When an already sensitised individual is re-exposed to a similar allergen, they are highly likely to experience allergic reactions. These hyperreactions can cause excessive tissue damage over time. 

What are the Different Types of Hypersensitivity Reactions?

To date, medical researchers have found four different types of hypersensitivity reactions. However, some studies suggest that a potential fifth type can exist. But, most recognised bodies prefer to include this fifth type as a subset of type 2 hypersensitivity reaction.  

Here are the major hypersensitivity types that you must be aware of:

1. Type 1 Hypersensitivity Reaction

This type of hypersensitivity reaction triggers an immediate response. It can happen when a person is directly susceptible to an antigen. In these circumstances, the concerned individual’s body responds to the antigen by forming a definite type of antibody, termed Immunoglobulin E (IgE). 

The following elements can activate type 1 hypersensitivity responses:

• Animal sources like rats, cats or bee stings
• Selected food products like seafood, nuts and soy
• Environmental agents like latex, dust, mould, etc.
• Allergic conditions like asthma, conjunctivitis, and allergic rhinitis

In this type of hypersensitivity, there is a sensitisation stage and an effect stage: 

• During the first stage, the person does not experience any symptoms. 
• However, the second stage is triggered by re-exposure, when the body finally recognises the antigen and generates a response as symptoms. 

Some common symptoms of a type 1 hypersensitivity reaction include:

• Rash
• Hives
• Flushing
• Itching
• Wheezing
• Oedema
• Stomach cramps
• Rhinitis

Treatment Options for Type 1 Hypersensitivity Reaction

To cure the above-mentioned effects, some people need immediate medical intervention. After the doctor suspects type 1 hypersensitivity, they first review the patient’s previous medical records before suggesting specific blood and allergy tests. 

Then, they provide treatment options like:

• Systemic glucocorticoids
• Adrenaline or epinephrine
• Antihistamines

Also, the concerned individuals must avoid the recognised allergen moving forward. 

2. Type 2 Hypersensitivity Reaction

Much similar to the type 1 hypersensitivity reaction,  type 2 reactions also result from antibodies. As a matter of fact: 

• Both type 2 and type 3 hypersensitivity are generated from the same category of antibodies, IgE. 
• The fundamental difference between type 2 and type 3 hypersensitivities lies in the type of antigen that triggers an immune response.

From a type 2 hypersensitivity, cytotoxic reactions take place where healthy cells are damaged as they encounter the antigens. This can lead to long-term tissue damage, causing conditions like:

• Autoimmune hemolytic anaemia occurs when the red blood cells (RBC) burst happens spontaneously 
• Thrombocytopenia or an acute blood disorder that occurs when there isn’t enough platelets
• Autoimmune conditions like Grave’s disease
• Autoimmune neutropenia, when the human body automatically destroys neutrophils responsible for healing infections

Treatment Options for Type 2 Hypersensitivity Reaction

Cephalosporins, penicillin, thiazides, and methyldopa are among the drugs that are known to induce type 2 hypersensitivity reactions. To prevent the unusual action of these antibodies, doctors can prescribe some treatment options, such as:

• Intravenous immunoglobulin infusions
• Systemic glucocorticoids
• Cyclophosphamide and cyclosporine agents
• Plasmapheresis

3. Type 3 Hypersensitivity Reaction

In this type of hypersensitivity, antibodies and antigens combine to produce complexes in the blood vessels, skin, kidney tissues and joints. A series of bodily reactions then follow, causing a great deal of tissue damage. 

Some causes of a type 3 hypersensitivity response can be:

• Intake of drugs that include proteins from various organisms, like antivenins
• A drug infliximab, which is often recommended for controlling autoimmune conditions
• Animal stimulations like tick bites or insect stings

The various side-effects of type 3 hypersensitivity can feature:

• Small-vessel vasculitis
• Rheumatoid arthritis
• Serum sickness
• Lupus
• Henoch-Schönlein purpura

Treatment Options for Type 3 Hypersensitivity Reaction

While treating type 3 hypersensitivity, doctors can do the following:

• Conduct different assessments that include blood and urine tests along with imaging scans. 
• Recommend different forms of immunosuppression with systemic glucocorticoids as well as some disease-modifying drugs based on the severity of the hypersensitivity response. 

4. Type 4 Hypersensitivity Reaction

Very different from the other forms of hypersensitivity, all type 4 hypersensitivity examples are cell-mediated. In contrast to antibody-caused reactions, type 4 hypersensitivity responses result from T cells. Medical experts further distinguish these reactions into 4a, 4b, 4c and 4d. 

Additionally, when compared to the other types of hypersensitivity, this type causes a delayed response. The three major subsets of type 4 hypersensitivity are:

• Tuberculin-type hypersensitivity
• Contact dermatitis
• Granulomatous-type hypersensitivity

The most common hypersensitivity reactions in this category are triggered by: 

• Exposure to certain metals 
• Poison ivy 
• Drugs like anticonvulsants or antibiotics 

Doctors can diagnose contact dermatitis by suggesting skin patch tests or a skin biopsy. However, experts are more likely to use a chest X-ray when treating tuberculin-type hypersensitivity.

However, it is tricky to diagnose granulomatous-type hypersensitivity, and healthcare providers often stick to the following assessments before starting their treatment:

• X-ray
• Lymph node biopsy
• Enzyme analysis
• Salivary gland test

Treatment Options for Type 4 Hypersensitivity Reaction

Doctors usually suggest the following treatment options for type 4 hypersensitivity reactions:

• If the patient is found to have contact dermatitis, then the healthcare provider can recommend availing topical steroids. 
• Similarly, the treatment specifics vary from one case to another. 
• For tuberculin-type hypersensitivity, pathologists typically resort to the regular method for diagnosing tuberculosis. 

Some typical treatments for tuberculin-type hypersensitivity are:

• Isoniazid
• Rifampin
• Ethambutol
• Pyrazinamide

Finally, granulomatous hypersensitivity treatment is approached as condition-specific, although in most cases, the doctors apply a steroid therapy.

Non Allergic Hypersensitivity Reaction

Some people can experience a non-immune anaphylactic reaction or non-allergic hypersensitivity to specific foods or drugs: 

• These reactions are a bit complex to identify separately, but they are often noticed as they result in direct symptoms. 
• Unlike allergic hypersensitivity reactions, they do not involve the release of T cells or antibodies. 

What is the Mechanism of Hypersensitivity?

As already discussed, hypersensitivity diseases are primarily segregated depending on the type of immune reaction and the underlying mechanism causing cell or tissue injuries. The mechanisms highlight some scenarios that are mainly reliant on antibodies while others rely on T cells. 

Depending on the way normal cellular functions are disrupted, these are the main hypersensitivity mechanisms observed to date:

1. Immediate Hypersensitivity (Type I)

This is an IgE-mediated allergic reaction triggered by allergens, leading to rapid mast cell degranulation and release of inflammatory mediators. It manifests as conditions like asthma, hay fever, and anaphylaxis.

2. Antibody-mediated Hypersensitivity (Type II)

This involves Immunoglobulin G (IgG) or Immunoglobulin M (IgM) antibodies binding to cells or tissues, causing damage through complement activation or antibody-dependent cellular cytotoxicity. 

Some instances include transfusion reactions and autoimmune hemolytic anaemia.

3. Immune Complex-mediated Hypersensitivity (Type III)

This occurs when antigen-antibody complexes deposit in tissues, activating complement and attracting neutrophils, resulting in inflammation and tissue damage.

4. T Cell-Mediated Hypersensitivity (Type IV)

Type 4 hypersensitivity is a delayed-type hypersensitivity mediated by T cells, which release cytokines and cause inflammation upon encountering an antigen.

FAQs About Hypersensitivity Reactions

1. What are the main differences between type I and type II hypersensitivity reactions?

Type I hypersensitivity is characterised by allergic reactions like anaphylaxis and hives. They are caused by IgE-mediated mechanisms, while type II hypersensitivity is a cytotoxic response caused by antibodies that result in long-term cell damage or tissue destruction. The latter symptoms are commonly noticed in autoimmune disorders. 

2. What are some common triggers for type IV hypersensitivity reactions?

A type four hypersensitivity reaction, a cell-mediated response to allergens like those in contact dermatitis or tuberculin skin tests, involves the activation of T cells that release inflammatory cytokines, causing a localised reaction.

3. What are the long-term effects of untreated hypersensitivity reactions?

Apart from the medically established symptoms, chronic allergies or untreated hypersensitivity can deteriorate the overall quality of life. Some possible symptoms are frequent respiratory issues, skin allergies and conditions, poor digestive health, and so on. 

4. What is a severe life-threatening hypersensitivity reaction?

Anaphylaxis is a life-threatening fatal hypersensitivity response. Its symptoms can arise within seconds or minutes after the sensitised person is exposed to the allergen. 

5. Does hypersensitivity go away?

It is possible for hypersensitivity to disappear, particularly when the root cause is discovered and avoided. However, recovery time and severity of the disease vary.

Conclusion

Hypersensitivity reactions can take a time frame of a few minutes to hours or even days to generate harmful symptoms. Luckily, most of them can be detected by timely diagnosis followed by proper medication and treatment. Thus, it is highly suggested to visit a trusted immunologist upon facing the above-mentioned symptoms. 

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