Hypersensitivity- Definition, Causes, Mechanism, Types, Examples

Hypersensitivity is a term that describes an abnormal or excessive immune response to a foreign substance, also known as an antigen. Hypersensitivity reactions can cause damage to the body`s own tissues and organs, and can sometimes be life-threatening. Hypersensitivity reactions are classified into four types (I-IV) based on the mechanism and timing of the immune response .

Hypersensitivity reactions can be triggered by various antigens, such as:

• Microbes, such as bacteria, viruses, fungi, and parasites
• Drugs, such as penicillin, aspirin, and insulin
• Foods, such as peanuts, eggs, and milk
• Pollen, dust mites, animal dander, and insect venom
• Transplanted organs or tissues
• Self antigens, such as in autoimmune diseases

Hypersensitivity reactions can affect different parts of the body, such as:

• Skin, causing rashes, hives, blisters, or eczema
• Respiratory system, causing asthma, hay fever, or anaphylaxis
• Blood vessels, causing vasculitis or shock
• Joints, causing arthritis or gout
• Kidneys, causing glomerulonephritis or nephrotic syndrome
• Nervous system, causing multiple sclerosis or Guillain-Barré syndrome

Hypersensitivity reactions can be diagnosed by various methods, such as:

• Skin tests, which involve applying a small amount of antigen to the skin and observing for a reaction
• Blood tests, which measure the levels of antibodies or immune cells in the blood
• Biopsy, which involves taking a sample of tissue and examining it under a microscope
• Challenge tests, which involve giving a small dose of antigen orally or intravenously and monitoring for symptoms

Hypersensitivity reactions can be treated by various methods, such as:

• Avoiding or eliminating the antigen that causes the reaction
• Taking medications that suppress or modulate the immune response, such as antihistamines, corticosteroids, or immunosuppressants
• Receiving immunotherapy or desensitization, which involves gradually exposing the body to increasing doses of antigen to induce tolerance
• Receiving emergency care for severe reactions, such as epinephrine injections or oxygen therapy

Hypersensitivity reactions are common and can affect anyone at any age. However, some people may have a genetic predisposition or environmental factors that increase their risk of developing hypersensitivity reactions. Hypersensitivity reactions can have a significant impact on the quality of life and well-being of affected individuals. Therefore, it is important to understand the causes, mechanisms, types, and management of hypersensitivity reactions.

Hypersensitivity is a condition in which the immune system reacts excessively or inappropriately to a foreign substance, called an antigen. The antigen can be anything that the body recognizes as foreign, such as a microbe, a food, a drug, a pollen, or a venom. Hypersensitivity can cause various symptoms and diseases, depending on the type of immune response and the affected tissues.

There are many factors that can cause or contribute to hypersensitivity, such as:

• Genetic predisposition: Some people inherit a tendency to produce more IgE antibodies or to have more reactive T cells, which can increase their risk of developing hypersensitivity reactions.
• Environmental exposure: Some antigens are more common or potent in certain environments, such as animal furs, dust mites, mold spores, or pollen. Repeated or prolonged exposure to these antigens can sensitize the immune system and trigger hypersensitivity reactions.
• Infection: Some infections can activate or re-activate latent viruses, such as herpes simplex virus (HSV) or human herpesvirus 6 (HHV-6), which can induce or exacerbate hypersensitivity reactions. Some infections can also mimic or cross-react with self antigens, leading to autoimmune hypersensitivity.
• Drug reaction: Some drugs can act as haptens, which are small molecules that bind to proteins and elicit an immune response. Some drugs can also induce cytotoxic antibodies or T cells that damage target cells. Some drugs can also form immune complexes with their metabolites or serum proteins, which can deposit in tissues and cause inflammation.
• Immunization: Some vaccines or immunotherapy can induce hypersensitivity reactions by stimulating the production of antibodies or T cells against the antigens. This can be beneficial for preventing infections, but it can also cause adverse reactions in some cases.

Hypersensitivity is not always predictable or preventable, but some measures can help reduce the risk or severity of the reactions, such as:

• Avoiding known allergens or triggers
• Taking antihistamines or corticosteroids to suppress the immune response
• Carrying an epinephrine auto-injector for emergency treatment of anaphylaxis
• Undergoing desensitization therapy to induce tolerance to specific antigens

Hypersensitivity reactions are immune responses that are exaggerated or inappropriate against an antigen or allergen. They occur when there is an imbalance between the effector mechanisms and the regulator mechanisms that normally operate to limit such reactions. Specific genes are associated with the development of type I hypersensitivity responses.

Hypersensitivity reactions are classified into four types according to the type of immune response and the effector mechanism responsible for cell and tissue injury. These mechanisms include some that are predominantly dependent on antibodies and others predominantly dependent on T cells, although a role for both humoral and cell-mediated immunity is often found in many hypersensitivity diseases.

• Type I hypersensitivity is caused by IgE antibodies specific for environmental antigens and is the most prevalent type of hypersensitivity disease. It is also known as immediate hypersensitivity or allergy. It involves the cross-linking of cell-bound IgE by di-(multi-) valent free antigen, which triggers the release of mediators (e.g., histamine, kininogen) from mast cells and basophils. These mediators induce vasodilation, smooth muscle contraction, mucus secretion, edema, and/or skin blisters .
• Type II hypersensitivity is caused by IgG and IgM antibodies specific for cell surface or extracellular matrix antigens. It is also known as antibody-mediated cytotoxic reaction. It involves the binding of antibodies to target antigens, which leads to tissue injury by activating the complement system, by recruiting inflammatory cells, or by interfering with normal cellular functions .
• Type III hypersensitivity is caused by IgM and IgG antibodies specific for soluble antigens in the blood. It is also known as immune complex-mediated reaction. It involves the formation of antigen-antibody complexes, which deposit in various tissues and cause inflammation, thrombosis, and tissue injury by activating the complement system and attracting leukocytes .
• Type IV hypersensitivity is caused by T lymphocytes that induce inflammation or directly kill target cells. It is also known as delayed-type hypersensitivity or cell-mediated hypersensitivity. It involves the activation of CD4+ helper T cells or CD8+ cytotoxic T cells, which secrete cytokines that promote inflammation and activate leukocytes, mainly macrophages and neutrophils .

In the next section, we will discuss each type of hypersensitivity reaction in more detail and provide some examples of clinical manifestations.

Hypersensitivity reactions are abnormal immune responses that cause damage to the body`s own tissues. They are classified into four major types, depending on the mechanism and the time course of the reaction. Each type involves different types of antigens, antibodies, and effector cells. The four types of hypersensitivity reactions are:

• Type I hypersensitivity: This is also known as immediate or anaphylactic hypersensitivity. It occurs within minutes of exposure to an antigen that triggers the production of IgE antibodies. These antibodies bind to mast cells and basophils, which release histamine and other inflammatory mediators that cause vasodilation, smooth muscle contraction, mucus secretion, and edema. Type I hypersensitivity reactions are responsible for allergic diseases such as asthma, allergic rhinitis, urticaria, and anaphylaxis .
• Type II hypersensitivity: This is also known as antibody-mediated or cytotoxic hypersensitivity. It occurs within hours to days of exposure to an antigen that binds to cell surface or extracellular matrix molecules. This triggers the activation of the complement system and/or the recruitment of phagocytes and natural killer cells that destroy the target cells. Type II hypersensitivity reactions are responsible for autoimmune diseases such as hemolytic anemia, Goodpasture`s syndrome, and myasthenia gravis .
• Type III hypersensitivity: This is also known as immune complex-mediated hypersensitivity. It occurs within hours to days of exposure to an antigen that forms soluble complexes with IgG or IgM antibodies. These complexes deposit in various tissues, especially blood vessels, where they activate the complement system and attract neutrophils and macrophages that cause inflammation and tissue damage. Type III hypersensitivity reactions are responsible for immune complex diseases such as serum sickness, systemic lupus erythematosus, and post-streptococcal glomerulonephritis .
• Type IV hypersensitivity: This is also known as cell-mediated or delayed-type hypersensitivity. It occurs within days to weeks of exposure to an antigen that activates T cells, especially CD4+ helper T cells and CD8+ cytotoxic T cells. These T cells secrete cytokines that induce inflammation and recruit other leukocytes that cause tissue damage. Type IV hypersensitivity reactions are responsible for delayed allergic reactions such as contact dermatitis, tuberculin test, and granuloma formation .

The table below summarizes the main features of each type of hypersensitivity reaction:

Type I hypersensitivity reaction is also known as an immediate reaction or anaphylaxis. It involves the production of immunoglobulin E (IgE) antibodies that bind to specific antigens (allergens) and trigger the release of inflammatory mediators from mast cells and basophils.

The reaction occurs in two stages: sensitization and effector. In the sensitization stage, the first exposure to an allergen stimulates the activation of helper T cells (Th2) that secrete cytokines such as interleukin-4 (IL-4) and interleukin-13 (IL-13). These cytokines promote the differentiation of B cells into plasma cells that produce IgE antibodies specific for the allergen. The IgE antibodies then bind to the high-affinity Fc receptors on the surface of mast cells and basophils, priming them for the next exposure.

In the effector stage, the subsequent exposure to the same allergen causes cross-linking of the IgE antibodies on the mast cells and basophils, leading to their degranulation and release of various mediators such as histamine, leukotrienes, prostaglandins, and cytokines. These mediators cause vasodilation, increased vascular permeability, smooth muscle contraction, mucus secretion, and activation of other inflammatory cells such as eosinophils and neutrophils. The result is a rapid onset of symptoms such as itching, urticaria, angioedema, bronchoconstriction, rhinitis, conjunctivitis, abdominal cramps, vomiting, diarrhea, hypotension, and shock. The reaction can be localized or systemic depending on the route and dose of allergen exposure.

Some examples of common allergens that can cause type I hypersensitivity reactions are:

• Pollen
• Dust mites
• Animal dander
• Insect venom
• Food (e.g., peanuts, shellfish, eggs)
• Drugs (e.g., penicillin, aspirin)

The diagnosis of type I hypersensitivity reaction is based on the history of exposure to a potential allergen and the presence of typical symptoms. Skin tests and blood tests can be used to confirm the presence of specific IgE antibodies to the suspected allergen. The treatment of type I hypersensitivity reaction involves avoiding or minimizing contact with the allergen, administering antihistamines or corticosteroids to reduce inflammation, and using epinephrine or bronchodilators to reverse life-threatening symptoms such as anaphylactic shock or asthma. Immunotherapy or desensitization can be considered for some patients who have severe or persistent allergic reactions that are not controlled by medication. This involves injecting gradually increasing doses of the allergen over a period of time to induce tolerance or reduce IgE production.

Type II hypersensitivity reaction refers to an immune reaction in which antibodies (IgG or IgM) are directed against antigens on the surface of cells or extracellular matrix, resulting in cellular destruction, functional loss, or tissue damage . The antigens involved may be endogenous (such as blood group antigens) or exogenous (such as drugs or microbes) . The antibodies can cause tissue injury by three different mechanisms:

• Complement activation: The binding of antibodies to the target antigens triggers the classical pathway of complement activation, leading to the formation of membrane attack complexes (MAC) that lyse the cells. The complement fragments C3a and C5a also act as anaphylatoxins that recruit and activate inflammatory cells such as neutrophils and macrophages . Examples of diseases caused by this mechanism include hemolytic anemia, hemolytic transfusion reactions, and hemolytic disease of the newborn .
• Antibody-dependent cellular cytotoxicity (ADCC): The Fc portion of the bound antibodies can interact with Fc receptors on the surface of natural killer (NK) cells, macrophages, neutrophils, or eosinophils, which then release cytotoxic molecules such as perforin, granzymes, reactive oxygen species, or enzymes that kill the target cells . Examples of diseases caused by this mechanism include autoimmune thyroiditis and chronic urticaria .
• Antibody-mediated cellular dysfunction: The binding of antibodies to cell surface receptors can interfere with their normal function, either by blocking or stimulating them. This can result in impaired or excessive cellular activity, without causing cell death . Examples of diseases caused by this mechanism include myasthenia gravis, Graves` disease, and Goodpasture`s syndrome .

Type II hypersensitivity reactions are usually acute and can cause severe tissue damage and organ failure. They can be diagnosed by detecting the presence of specific antibodies in the serum or on the surface of the affected cells. They can be treated by removing the offending antigen (if possible), suppressing the immune response with corticosteroids or immunosuppressive drugs, or replacing the damaged cells or organs (such as blood transfusion or transplantation) .

Type IV hypersensitivity reaction, also called delayed-type hypersensitivity, is a type of hypersensitivity reaction that can take a day or more to develop . Unlike the other types, it is not humoral (not antibody-mediated) but rather is a type of cell-mediated response. This response involves the interaction of T cells, monocytes, and macrophages .

The mechanism of type IV hypersensitivity reaction involves the following steps :

• Sensitization phase: An antigen (usually a protein or a hapten) enters the body and is processed by antigen-presenting cells (APCs), such as dendritic cells or macrophages. The APCs present the antigen to naive CD4+ T cells in the lymph nodes, which differentiate into effector T cells (mainly Th1 and Th17 subsets). The effector T cells then migrate to the site of antigen exposure and circulate in the blood. This phase takes about 10 to 14 days after the first exposure to the antigen.
• Elicitation phase: Upon re-exposure to the same antigen, the effector T cells recognize it and become activated. They secrete various cytokines (such as IFN-gamma, TNF-alpha, IL-17, and IL-22) that recruit and activate other inflammatory cells (such as macrophages, neutrophils, eosinophils, and basophils). The inflammatory cells release more cytokines, chemokines, and reactive oxygen species that cause tissue damage and inflammation. This phase usually occurs 24 to 72 hours after the second exposure to the antigen .

Type IV hypersensitivity reaction can be further classified into four subtypes based on the type of T cells and cytokines involved:

• Type IVa: Th1-mediated reaction that involves IFN-gamma and TNF-alpha. It causes macrophage activation and granuloma formation. Examples are tuberculin skin test, contact dermatitis, and granulomatous diseases (such as tuberculosis and sarcoidosis).
• Type IVb: Th2-mediated reaction that involves IL-4, IL-5, and IL-13. It causes eosinophil activation and recruitment. Examples are chronic asthma and allergic rhinitis.
• Type IVc: Cytotoxic T cell-mediated reaction that involves perforin and granzymes. It causes direct killing of target cells. Examples are viral hepatitis, type 1 diabetes mellitus, and graft rejection.
• Type IVd: Neutrophil-mediated reaction that involves IL-8 and leukotriene B4. It causes neutrophil activation and recruitment. Examples are pustular skin diseases (such as acne vulgaris and hidradenitis suppurativa).

Some examples of type IV hypersensitivity reactions are:

• Tuberculin skin test: A purified protein derivative (PPD) of Mycobacterium tuberculosis is injected intradermally into a person who has been exposed to the bacterium before. The person develops a red, swollen, and hard lesion at the injection site within 48 to 72 hours due to Th1-mediated inflammation.
• Contact dermatitis: A person who is sensitized to a substance (such as nickel, poison ivy, or latex) develops an itchy, red, and blistering rash at the site of contact with the substance within 24 to 48 hours due to Th1-mediated inflammation.
• Drug hypersensitivity: A person who is sensitized to a drug (such as penicillin or sulfonamides) develops a fever, rash, lymphadenopathy, and organ dysfunction within a few days to weeks after taking the drug due to various mechanisms involving T cells.

Hypersensitivity reactions are abnormal and exaggerated immune responses to antigens that can cause tissue damage and disease. There are four main types of hypersensitivity reactions, each with different mechanisms and clinical manifestations. Here are some examples of each type:

• Type I hypersensitivity reaction: This is an immediate allergic reaction mediated by IgE antibodies that bind to mast cells and basophils and cause them to release histamine and other inflammatory mediators. Examples of type I hypersensitivity reactions include food allergies, venom allergies, drug allergies, latex allergies, and anaphylaxis.
• Type II hypersensitivity reaction: This is a cytotoxic reaction mediated by IgG or IgM antibodies that bind to antigens on the surface of cells or tissues and cause their destruction by complement activation, phagocytosis, or antibody-dependent cell-mediated cytotoxicity. Examples of type II hypersensitivity reactions include autoimmune hemolytic anemia, immune thrombocytopenia, Goodpasture syndrome, rheumatic fever, Graves disease, and myasthenia gravis .
• Type III hypersensitivity reaction: This is an immune complex-mediated reaction mediated by IgG antibodies that bind to soluble antigens in the circulation and form immune complexes that deposit in various tissues and cause inflammation, thrombosis, and tissue injury. Examples of type III hypersensitivity reactions include serum sickness, systemic lupus erythematosus, poststreptococcal glomerulonephritis, and some forms of vasculitis .
• Type IV hypersensitivity reaction: This is a delayed-type hypersensitivity reaction mediated by sensitized T cells that recognize antigens presented by antigen-presenting cells and secrete cytokines that recruit and activate macrophages and other inflammatory cells. Examples of type IV hypersensitivity reactions include allergic contact dermatitis, tuberculin skin test, granuloma formation, and some forms of transplant rejection .

Hypersensitivity reactions can be diagnosed by history, physical examination, skin tests, blood tests, and biopsy. Treatment depends on the type and severity of the reaction and may include antihistamines, corticosteroids, immunosuppressants, epinephrine, desensitization therapy, or avoidance of the trigger antigen. Hypersensitivity reactions can be life-threatening if not recognized and treated promptly. Therefore, it is important to educate patients about the signs and symptoms of hypersensitivity reactions and how to prevent them.

We are Compiling this Section. Thanks for your understanding.