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- Main effector cells in type IV hypersensitivity
- Become activated after encounter antigen that they are sensitized to
- Activated T cells release cytokines to recruit and activate other immune cells

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https://www.britannica.com/science/immune-system-disorder/Type-IV-hypersensitivity

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Type IV hypersensitivity is a cell-mediated immune reaction. In other words, it does not involve the participation of antibodies but is due primarily to the interaction of T cells with antigens. Reactions of this kind depend on the presence in the circulation of a sufficient number of T cells able to recognize the antigen. The specific T cells must migrate to the site where the antigen is present. Since this process takes more time than reactions involving antibodies, type IV reactions first were distinguished by their delayed onset and are still frequently referred to as delayed hypersensitivity reactions. Type IV reactions not only develop slowly-reactions appear about 18 to 24 hours after introduction of antigen to the system-but, depending on whether the antigen persists or is removed, they can be prolonged or relatively transient.

The T cells involved in type IV reactions are memory cells derived from prior stimulation by the same antigen. These cells persist for many months or years, so that persons who have become hypersensitive to an antigen tend to remain so. When T cells are restimulated by this antigen presented on the surface of the macrophages (or on other cells that can express class II MHC molecules), the T cells secrete cytokines that recruit and activate lymphocytes and phagocytic cells, which carry out the cell-mediated immune response. Two common examples of delayed hypersensitivity that illustrate the various consequences of type IV reactions are tuberculin-type and contact hypersensitivity.

Tuberculin-type hypersensitivity

The tuberculin test is based on a delayed hypersensitivity reaction. The test is used to determine whether an individual has been infected with the causative agent of tuberculosis, Mycobacterium tuberculosis. (A previously infected individual would harbour reactive T cells in the blood.) In this test, small amounts of protein extracted from the mycobacterium are injected into the skin. If reactive T cells are present-i.e., the test is positive-redness and swelling appear at the injection site the next day, increase through the following day, and then gradually fade away. If a tissue sample from the site of the positive reaction is examined, it will show infiltration by lymphocytes and monocytes, increased fluid between the fibrous structures of the skin, and some cell death. If the reaction is more severe and prolonged, some of the activated macrophages will have fused together to form large cells containing several nuclei. An accumulation of activated macrophages of this sort is termed a granuloma. Immunity to a number of other diseases (for example, leprosy, leishmaniasis, coccidiosis, and brucellosis) also can be gauged by the presence or absence of a delayed reaction to a test injection of the appropriate antigen. In all these cases, the test antigen provokes only a transitory response when the test is positive and, of course, no response at all when the test is negative.

The same cell-mediated mechanisms are elicited by an actual infection with the living microbes, in which case the inflammatory response continues and the ensuing tissue damage and granuloma formation can cause serious damage. Moreover, in an actual infection, the microbes are often present inside the macrophages and are not necessarily localized in the skin. Large granulomas develop when the stimulus persists, especially if undegradable particulate materials are present and several macrophages, all attempting to ingest the same material, have fused their cell membranes to one another. The macrophages continue to secrete enzymes capable of breaking down proteins, and the normal structure of tissues in their neighbourhood becomes distorted. Although granuloma formation may be an effective method the immune system employs to sequester indigestible materials (whether or not of microbial origin) from the rest of the body, the harm inflicted by this immune mechanism may be much more serious than the damage caused by the infectious organisms. This is the case in such diseases as pulmonary tuberculosis and schistosomiasis and in certain fungal infections that become established within the body tissues rather than at their surface.

In contact hypersensitivity, inflammation occurs when the sensitizing chemical comes in contact with the skin surface. The chemical interacts with proteins of the body, altering them so that they appear foreign to the immune system. A variety of chemicals can cause this type of reaction. They include various drugs, excretions from certain plants, metals such as chromium, nickel, and mercury, and industrial products such as hair dyes, varnish, cosmetics, and resins. All these diverse substances are similar in that they can diffuse through the skin. One of the best-known examples of a plant that can provoke a contact hypersensitivity reaction is poison ivy ( Toxicodendron radicans), found throughout North America. It secretes an oil called urushiol, which is also produced by poison oak ( T. diversilobum), the poison primrose ( Primula obconica), and the lacquer tree ( T. vernicifluum). When urushiol comes in contact with the skin, it initiates the contact hypersensitivity reaction.

As sensitizing chemicals diffuse into the skin, they react with some proteins of the body, changing the antigenic properties of the protein. The chemical can interact with proteins located in both the outer horny layer of the skin ( dermis) and the underlying tissue ( epidermis). Some of the epidermal protein complexes migrate to the draining lymph nodes, where they stimulate T cells responsive to the newly formed antigen to multiply. When the T cells leave the nodes to enter the bloodstream, they can travel back to the site where the chemical entered the body. If some of the sensitizing substance remains there, it can reactivate the T cells, inducing a recurrence of inflammation. The clinical result is contact dermatitis, which can persist for many days or weeks. Treatment is by local application of corticosteroids, which greatly diminish lymphocyte infiltration, and by avoidance of further contact with the sensitizing agent.

Although delayed hypersensitivity can be a nuisance when it produces skin allergies, it is an important part of the immune defense against intracellular parasites, and it may also play a role in the containment of some tumours.

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Immune system disorder - Type IV Hypersensitivity

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immune system disorder - Immune system disorder - Type IV Hypersensitivity: Type IV hypersensitivity is a cell-mediated immune reaction. In other words, it does not involve the participation of antibodies but is due primarily to the interaction of T cells with antigens.

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Contact dermatitis ( when skin comes in contact with poison ivy, poison oak or nickel) , Fever, Pain, Swelling, Rash, Heart, liver and kidney problems ,Fatigue, Nausea, Diarrhea. Vomiting,

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https://healthinfo.healthengine.com.au/hypersensitivity-reaction-type-iv

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What is Hypersensitivity Reaction Type IV

Hypersensitivity means that the body responds to a particular substance (called allergens) in an exaggerated fashion, where it does not happen in normal circumstances. There are 4 types of hypersensitivity reaction, type I, II, III and IV. They are different in terms of the disease manifestation and pathological processes. However, only type IV hypersensitivity reaction will be discussed here.
Type IV hypersensitivity reaction is also called delayed type hypersensitivity reaction because it takes 2 to 3 days for the reaction to develop after exposure to the particular substance.
Type IV hypersensitivity reaction can occur in many parts of the body. Generally, they include:

The image below is that of a reaction to the allergen latex:

Statistics on Hypersensitivity Reaction Type IV

Type IV hypersensitivity diseases are common, but less common than type 1 hypersensitivity reaction diseases.

Risk Factors for Hypersensitivity Reaction Type IV

Depending on the manifestations of different type IV hypersensitivity diseases, there are different risk factors as well.
Some diseases are more common in women such as autoimmune diseases. Some are more common in men such as allergic contact dermatitis. The exact mechanism of such discrepancies is unknown.
Likewise, ethnic and geographical differences have roles to play in different diseases.

Progression of Hypersensitivity Reaction Type IV

Type IV hypersensitivity is characterized by cell-mediated response rather than antibodies as in other types of hypersensitivity reactions. Specifically, the T lymphocytes are involved in the development of the sensitivity, hence called cell-mediated hypersensitivity. T lymphocytes are white blood cells in the body.
After exposure to antigens, through a series of biochemical events, the T-cells will be activated. By releasing some chemicals, the T cells activate other white blood cells to mount an immune response.
This entire cascade of reactions take 2-3 days to develop and is different from other types of hypersensitivity reactions.

How is Hypersensitivity Reaction Type IV Diagnosed?

Depending on the different type of diseases, some general investigations may be necessary. Basic routine investigations may include looking at the blood function, liver function, thyroid function and kidney function.

Prognosis of Hypersensitivity Reaction Type IV

Type IV hypersensitivity diseases are usually long-standing and require on-going treatment if there is flaring up of the diseases. However it does not cause life-threatening conditions such as anaphylaxis or angioedema (in type I hypersensitivity diseases).

How is Hypersensitivity Reaction Type IV Treated?

There is no cure for these diseases, the treatment aims at symptom control only. Although type IV hypersensitivity diseases can cause significant inconvenience in terms of their signs and symptoms, with good treatment plan the most of the diseases can be well-controlled.
Depending on the severity of the allergic reaction, different treatment approaches are applied. Treatment options, either given alone or in combination, include the following:

Allergen avoidance: prevention and avoidance of possible triggers are the mainstay of the treatment. However this is impractical in some diseases such as allergic contact dermatitis because some of the substance cannot be identified and remained unknown for a long period of time. However if known this is a useful and effective method for diseases with known external allergen. This is not applicable for T-cell mediated autoimmune diseases such as type 1 diabetes mellitus.

Steroids: these drugs are used for late phase of allergic reaction, and they include prednisolone, dexamethasone, etc. Depending on the diseases, steroid could become a long-term medication. In such cases, long term use will need medical supervision for monitoring of potential side effects.

Other drugs that alter the body's immune system include interferon, cyclophosphamide, cyclosporine, etc. These drugs are used under specialist supervision.

Hypersensitivity Reaction Type IV References

1. Braunwald E et al. Harrison's principles of internal medicine. 15th ed. New York; McGraw-Hill; 2001.

2. Cohen DE, Brancaccio RR, Soter NA: Diagnostic tests for type IV or delayed hypersensitivity reactions. Clin Allergy Immunol 2000; 15: 287-305.

3. Middleton E Jr, Reed CE, Ellis EF, et al, eds: Allergy: Principles and Practice. 5th ed. St. Louis, Mo: Mosby-Year Book; 1998.

4. The Merck Manual: Disorders with Type I Hypersensitivity Reactions [online]. 2005. [Cited 2005 October 9th]. Available from: http://www.merck.com/mrkshared/mmanual/section12/chapter148/148b.jsp

5. Up to Date: Clinical features of rheumatoid arthritis [online]. 2005. [Cited 2005 October 9th]. Available from: http://www.utdol.com/application/topic.asp?file=rheumart/3022&type=A&selectedTitle=1~209

6. Wilkinson JD, Rycroft RJG. Contact dermatitis. In: Champion RH, Burton JL, Ebling FJG, editors. Rook/Wilkinson/Ebling textbook of dermatology. 5th ed. Oxford: Blackwell Scientific Publications, 1992:611-715.

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Type IV hypersensitivity reaction information | myVMC

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Hypersensitivity reaction type IV is an allergic reaction (e.g. contact dermatitis) that occurs due to overactivity of immune cells called T lymphocytes.

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Type IV Hypersensitivity Reaction - PubMed (nih.gov)

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In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan.

Affiliations

¹ University of science and technology - Yemen

² Icahn School of Medicine at Mount Sinai , The Brooklyn Hospital Center

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In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan.

Affiliations

¹ University of science and technology - Yemen

² Icahn School of Medicine at Mount Sinai , The Brooklyn Hospital Center

Excerpt

Our immune system plays a crucial role in protecting our body against pathogens, but sometimes there is an exaggerated response. This exaggerated response is triggered by the interaction of the immune system with an antigen (allergen) and is referred to as hypersensitivity. Hypersensitivity reactions are classified into four types by Coombs and Gell. The first three types are considered immediate hypersensitivity reactions because they occur within 24 hours. The fourth type is considered a delayed hypersensitivity reaction because it usually occurs more than 12 hours after exposure to the allergen, with a maximal reaction time between 48 and 72 hours. The four types of hypersensitivity are:

1. Type I: reaction mediated by IgE antibodies

2. Type II: cytotoxic reaction mediated by IgG or IgM antibodies

3. Type III: reaction mediated by immune complexes

4. Type IV: delayed reaction mediated by cellular response

A Type IV hypersensitivity reaction is mediated by T cells that provoke an inflammatory reaction against exogenous or endogenous antigens. In certain situations, other cells, such as monocytes, eosinophils, and neutrophils, can be involved. After antigen exposure, an initial local immune and inflammatory response occurs that attracts leukocytes. The antigen engulfed by the macrophages and monocytes is presented to T cells, which then becomes sensitized and activated. These cells then release cytokines and chemokines, which can cause tissue damage and may result in illnesses. Examples of illnesses resulting from type IV hypersensitivity reactions include contact dermatitis and drug hypersensitivity. Type IV reactions are further subdivided into type IVa, IVb, IVc, and IVd based on the type of T cell (CD4 T-helper type 1 and type 2 cells) involved and the cytokines/chemokines produced.

Delayed hypersensitivity plays a crucial role in our body's ability to fight various intracellular pathogens such as mycobacteria and fungi. They also play a principal role in tumor immunity and transplant rejection. Since patients with acquired immunodeficiency syndrome (AIDS) have a progressive decline in the number of CD4 cells, they also have a defective type four hypersensitivity reaction.

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Conflict of interest statement

Disclosure: Khaled Marwa declares no relevant financial relationships with ineligible companies.

Disclosure: Noah Kondamudi declares no relevant financial relationships with ineligible companies.

References

Pichler WJ. Delayed drug hypersensitivity reactions. Ann Intern Med. 2003 Oct 21;139(8):683-93. - PubMed

Justiz Vaillant AA, Vashisht R, Zito PM. StatPearls [Internet] StatPearls Publishing; Treasure Island (FL): 2023. May 29, Immediate Hypersensitivity Reactions. - PubMed

Usman N, Annamaraju P. StatPearls [Internet] StatPearls Publishing; Treasure Island (FL): 2023. May 22, Type III Hypersensitivity Reaction. - PubMed

Czarnobilska E, Obtułowicz K, Wsołek K. [Type IV of hypersensitivity and its subtypes]. Przegl Lek. 2007;64(7-8):506-8. - PubMed

Sommer S, Wilkinson SM, Beck MH, English JS, Gawkrodger DJ, Green C. Type IV hypersensitivity reactions to natural rubber latex: results of a multicentre study. Br J Dermatol. 2002 Jan;146(1):114-7. - PubMed

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national center for biotechnology information

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Type IV Hypersensitivity Reaction - PubMed

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Our immune system plays a crucial role in protecting our body against pathogens, but sometimes there is an exaggerated response. This exaggerated response is triggered by the interaction of the immune system with an antigen (allergen) and is referred to as hypersensitivity. Hypersensitivity reaction ...

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- drugs that suppress the immune system
- prevent type IV hypersensitivity from happening again

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- avoid exposure to allergens that trigger the response
- change habits, products, or use hypoallergic alternatives

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- a type of medication (corticosteroid cream or ointment) that reduces inflammation, itching and redness
- used to treat contact dermatitis which is a type of skin reaction caused by type IV hypersensitivity

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- a stronger form of corticosteroids
- used to treat more severe cases of type IV hypersensitivity

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Type IV hypersensitivity is also known as delayed type or cell-mediated hypersensitivity.

The initiator of this reaction would be the sensitized T cells. Upon the presence of antigen in the skin, antigen-presenting cells (APCs) would process and present it to the helper T cell. Upon exposure to the antigen, sensitive helper T cells would release cytokines, thus activating macrophages and other immune cells. Moreover, cytotoxic T cell is also activated which mediate direct cellular damage. This causes visible lesions at the site of the antigen present.

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- Phagocytic cells that engulf and destroy foreign invaders
- Activated by cytokines released from T cells
- Activated macrophages release their own cytokines -> further amplifies immune response

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- Granulocytes that are involved in early stages of inflammation
- Attracted to site of inflammation -> cytokines released by T cells and macrophages
- Release enzymes and ROS -> can damage tissue

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- Antigen-presenting cells -> capture and process antigens
- Present antigens to T cells -> trigger type IV hypersensitivity reaction