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Difference Between Type 1 Hypersensitivity and Type 4 Hypersensitivity

After a person is exposed to an antigen ((foreign substance which induces an immune response in the body), type 1 hypersensitivity develops and causes an instant reaction. In this kind of reaction, the body makes an Immunoglobulin E (IgE) specific form of antibody in response to an antigen.

Type 1 hypersensitivity reactions are triggered by a variety of substances, including antigens from soya, shrimps, bee stings, allergic asthma, mold, dust and conjunctivitis.

Type 4 hypersensitivity reactions are cell-mediated (relating to the immune response that is mediated by T cells rather than by antibodies released by B cells) in contrast to the other types.

T cells (WBCs) regulate type 4 hypersensitivity reactions instead of antibodies (protective proteins produced by your immune system)

The following are the 3 subsets of type 4 hypersensitivity:

  • Hypersensitivity (undesirable reactions produced by the normal immune system) of the tuberculin type to contact dermatitis
  • hypersensitivity (undesirable reactions produced by the normal immune system) of the granulomatous kind
  • Type 4 hypersensitivity (undesirable reactions produced by the normal immune system) reactions can be brought on by exposure to poison ivy, some metals, and drugs like antibiotics or anticonvulsants, among other things.

Type 1 hypersensitivity 

Type I hypersensitivity is also called as immediate hypersensitivity.

One antibody = IgE

Causes mast cells to release histamine

Type 1 = Immunoglobulin E (IgE)  = Mast cells = Histamine

Type 4 hypersensitivity

Four T cells like to raid but the response is more delayed

Type 4 = CD4 T cells = Delayed

Difference between Type 1 hypersensitivity and Type 4 hypersensitivity


Type 1 hypersensitivity 

  • Reaction mediated by Immunoglobulin E (IgE) antibodies.
  • Time to initiate is two to thirty minutes
  • This form of hypersensitivity is immediate
  • The antigen (foreign substance which induces an immune response in the body) form liquid antigen
  • Activation mechanism: specific to allergens Immunoglobulin E (IgE) Ab use the Fc (fragment crystallizable) receptor on mast cells to bind to them. When a particular allergen binds to Immunoglobulin E (IgE), Immunoglobulin E (IgE) cross-linking causes mast cell degranulation.
  • Food allergy to fish, soya, eggs, or peanuts.

Type 4 hypersensitivity

  • Delayed reaction 
  • T-cells are immune reactants
  • It is postponed hypersensitivity class
  • The antigen forms cellularly or soluble antigen
  • Activation mechanism – T helper (Th) cells (TH1 cells) release cytokines that cause cytotoxic T cells (a type of immune cell that destroys cells infected with viruses) and macrophages to become active
  • 24-72 hours are required for initiation
  • Example: Testing for brucellosis with brucellin and Mantoux test (tuberculosis diagnosis), Tuberculin test (tuberculosis diagnosis), Mallein test (glands diagnosis), Johnin test (Johnes disease diagnosis)


Type 1 hypersensitivity 

  • Pulmonary reactions (hypoxia)
  • Hay fever or Nasal allergic rhinitis 
  • Soft tissue angioedema
  • Allergic rhino conjunctivitis
  • Allergic asthma 
  • Local and systemic anaphylaxis

Type 4 hypersensitivity


Type 1 hypersensitivity 

Within 1 hour

Type 4 hypersensitivity

Days to weeks


The points of difference between Type 1 hypersensitivity and Type 4 hypersensitivity have been summarized as below:


What is Type 4 hypersensitivity?

A type 4 hypersensitivity reaction, or cell-mediated (relating to the immune response that is mediated by T cells rather than by antibodies released by B cells) reaction, can happen in response to specific allergens (allergens are antigen types that release an abnormally vigorous immune response) that have been in contact with the skin, resulting a condition termed as contact dermatitis (a red, itchy skin disorder that happens as a reaction to a chemical substance), or in response to several diagnostic methodologies, such as the tuberculin skin test (test to figure out if there are conditions of tuberculosis (TB) bacteria). It is important to keep a check on certain allergies to control this condition.

What is Type 4 hypersensitivity with examples?

  • Contact dermatitis – an itchy rash due to direct contact with an allergic reaction to it. 
  • Poison ivy – caused by an allergic reaction to urushiol
  • Tuberculin skin test – test to ascertain whether a person is infected with Mycobacterium tuberculosis
  • Some drug reactions, such as allopurinol.

What are types of type 1 hypersensitivity?

  • Atopic diseases – allergic asthma, angioedema, anaphylaxis, urticaria, conjunctivitis, and dermatitis
  • Nausea and vomiting
  • Shortness of breath

What happens in a Type 4 hypersensitivity reaction?

A type 4 hypersensitivity reaction, or cell-mediated (the immune response that does not use antibodies) reaction, can occur in response to particular allergens that have been in contact with the epidermis, termed as a disorder termed as contact dermatitis, or in response to specific diagnostic methodologies, like the tuberculin skin test. Tumor necrosis factor (TNF) -, which is released by the hyperactivated macrophages (macrophages with enhanced ability to dispose of invaders) attracts multiple monocytes (a type of leukocyte or white blood cell) to the infection site. While walling off (partitioned) the infected cells, these cells differentiate into epithelioid cells (the hallmark of hepatic granulomas), which cause serious localized inflammation and damage.

Does Type 4 hypersensitivity use antibodies?

Type IV hypersensitivity does not involve the participation of antibodies 

Is penicillin Allergy Type 4 hypersensitivity?

No, the penicillin allergy is mediated by a type 1 hypersensitivity reaction.

How do you test for Type 4 hypersensitivity?

Tuberculin test – involves injecting of a tiny quantity of fluid termed as tuberculin into the upper most layer of the skin epidermis on your forearm to find out if you have been infected with tuberculosis (TB) bacteria.

How do you control Type 4 hypersensitivity?

  • medications like corticosteroids
  • Allergen avoidance
  • Steroids – prednisolone, dexamethasone, etc.

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References :

[0]Farver, K., Morris, D. O., Shofer, F., & Esch, B. (2005). Humoral measurement of type‐1 hypersensitivity reactions to a commercial Malassezia allergen. Veterinary Dermatology, 16(4), 261-268.

[1]Ludwig, R. J., Schindewolf, M., Utikal, J., Lindhoff-Last, E., & Boehncke, W. H. (2006). Management of cutaneous type IV hypersensitivity reactions induced by heparin. Thrombosis and haemostasis, 96(11), 611-617.

[2]Morris, D. O., Olivier, N. B., & Rosser, E. J. (1998). Type-1 hypersensitivity reactions to Malassezia pachydermatis extracts in atopic dogs. American Journal of Veterinary Research, 59(7), 836-841.

[3]Simsek, M., Atas, E., BAĞRIAÇIK, E., Gunal, A., & Unay, B. (2020). Type 4 hypersensitivity development in a case due to mifamurtide. Turkish Journal of Pediatrics, 62(4).

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