Hypersensitivity types I to IV: the four effectors
Hypersensitivity types I to IV sort allergic and immune damage by what does the harm: IgE, antibody on cells, immune complexes or T cells. Timing is the clue.
Classify hypersensitivity reactions I to IV by effector mechanism and timing, and match the classic examples to each (Gell and Coombs).
The short version
- Hypersensitivity is an exaggerated adaptive immune response that damages the host; the Gell and Coombs classification sorts it into four types by effector.
- Type I is IgE on mast cells and starts within seconds to minutes; type II is IgG or IgM against cell or matrix antigens; type III is immune complexes.
- Type IV is T cell mediated, needs no antibody and peaks at 48 to 72 hours.
- Serum sickness is a type III reaction to a first exposure to a foreign protein and takes about one to two weeks to appear.
- The memory aid ACID gives anaphylactic, cytotoxic, immune complex, delayed for types I to IV.
Hypersensitivity types I to IV: two neighbours, two weapons
A man is stung by a bee, and within minutes he is wheezing and covered in hives. His neighbour brushes against poison ivy, and two days later has an itchy, blistering rash.
Both are called allergic, but the immune system used completely different weapons. The hypersensitivity types I to IV are the way to tell them apart, and the clue that sorts them is what does the damage and how long it takes.[1][2]
What hypersensitivity means: the Gell and Coombs classification
Hypersensitivity means an exaggerated adaptive immune response that damages the host.[1][2]
The Gell and Coombs classification sorts it by the effector: IgE, antibody on cells, immune complexes, or T cells.[1]
| Type | Effector | Timing | Examples |
|---|---|---|---|
| I | IgE on mast cells | Seconds to minutes | Anaphylaxis, allergic rhinitis, urticaria, food allergy |
| II | IgG or IgM against cell or matrix antigens | Minutes to hours if antibody is already present (for example a mismatched transfusion); chronic in autoimmune forms | Autoimmune haemolytic anaemia, Goodpasture syndrome |
| III | Immune complexes (soluble antigen and antibody) | About one to two weeks for serum sickness; hours for the Arthus reaction | Lupus, post-streptococcal glomerulonephritis, serum sickness |
| IV | T cells, no antibody needed | Peaks at 48 to 72 hours | Contact dermatitis, tuberculin skin test |
Type I: IgE, mast cells and histamine
Type I is immediate and IgE-mediated. Earlier exposure makes IgE, and that IgE sits on mast cells.[2]
On re-exposure, the allergen cross-links the IgE, the mast cell degranulates and releases histamine, and symptoms start within seconds to minutes.[2]
Think anaphylaxis, allergic rhinitis, urticaria and food allergy.
Type II: antibody against the body's own cells or matrix
In type II, IgG or IgM binds a fixed antigen on a cell or in the matrix. That triggers complement lysis, phagocytosis, or antibody-dependent cell killing.[1][2]
Autoimmune haemolytic anaemia and Goodpasture syndrome are examples.
Sometimes the antibody does not kill but disturbs function. It stimulates the receptor in Graves disease, and blocks it in myasthenia gravis.[2][5]
Type III: immune complexes, serum sickness and the Arthus reaction
Type III is soluble antigen and antibody forming immune complexes. The complexes lodge in vessel walls, joints and glomeruli, activate complement and call in neutrophils, which damage the tissue.[1]
Examples are lupus, post-streptococcal glomerulonephritis and serum sickness.
Serum sickness follows a first exposure to a foreign protein, and the delay is the clue: about one to two weeks, while antibody is made.[3][4]
A related local version is the Arthus reaction, a painful, swollen patch at an injection site within hours, in someone who already has antibody.[4]
Type IV: delayed, T cell mediated, 48 to 72 hours
Type IV is delayed and T cell mediated, with no antibody needed. Memory T cells recognise antigen and release interferon gamma and other cytokines that activate macrophages, or cytotoxic T cells kill directly.[2]
It peaks at 48 to 72 hours. Examples are contact dermatitis, such as poison ivy, and the tuberculin skin test.[2]
- Bee sting, wheeze and hives within minutes: IgE on mast cells, so type I
- Poison ivy, rash two days later: about 48 hours, T cells, so type IV, contact dermatitis
The ACID memory aid and timing as the clue
A memory aid is ACID: anaphylactic, cytotoxic, immune complex, delayed, for types I to IV.
Practice question
Original · USMLE styleA 41-year-old man is bitten by a snake and given an antivenom made from animal serum. Eleven days later he has fever, a urticarial rash and painful swollen joints. His serum C3 concentration is low, and his urine has mild proteinuria.
Common questions
What are the four types of hypersensitivity?
Type I is IgE-mediated, type II is antibody against cells or matrix, type III is immune complexes, and type IV is T cell mediated. This is the Gell and Coombs classification.
What does ACID stand for in hypersensitivity?
Anaphylactic, cytotoxic, immune complex and delayed, for types I, II, III and IV.
How long does a type IV hypersensitivity reaction take?
It is delayed and peaks at 48 to 72 hours after re-exposure. Contact dermatitis and the tuberculin skin test are examples.
What is the difference between serum sickness and the Arthus reaction?
Both are type III. Serum sickness follows a foreign protein and appears after about one to two weeks, while antibody is made. The Arthus reaction is a local painful, swollen patch at an injection site within hours, in someone who already has antibody.
Which hypersensitivity type includes Graves disease and myasthenia gravis?
Type II. Here the antibody does not kill but disturbs function: it stimulates the receptor in Graves disease and blocks it in myasthenia gravis.
Transcript
Read the full narration, by chapter648 words
0:00Two neighbours, two different weapons
A man is stung by a bee, and within minutes he is wheezing and covered in hives. His neighbour brushes against poison ivy, and 2 days later has an itchy, blistering rash. Both are called allergic, but the immune system used completely different weapons.
0:17Today: hypersensitivity and the four effectors
Today: classify hypersensitivity reactions into types one to four by their effector mechanism and timing. Hypersensitivity means an exaggerated adaptive immune response that damages the host. The Gell and Coombs classification sorts it by what does the damage: IgE, antibody on cells, immune complexes, or T cells. Type one is immediate and
0:41Type I: IgE, mast cells, histamine, seconds to minutes
IgE-mediated. Earlier exposure makes IgE, and that IgE sits on mast cells. On re-exposure, the allergen cross-links the IgE, the mast cell degranulates and releases histamine, and symptoms start within seconds to minutes. Think anaphylaxis, allergic rhinitis, urticaria and food allergy.
1:06Type II: antibody on cells, and receptor stimulation or blockade
Type two is antibody against the body's own cells or matrix. IgG or IgM binds a fixed antigen. That triggers complement lysis, phagocytosis, or antibody-dependent cell killing. Autoimmune haemolytic anaemia and Goodpasture syndrome are examples. Sometimes the antibody does not kill but disturbs function: it stimulates the receptor in Graves disease, and blocks it in myasthenia gravis. Type three is soluble antigen and antibody
1:36Type III: immune complexes, serum sickness and Arthus
forming immune complexes. The complexes lodge in vessel walls, joints and glomeruli, activate complement and call in neutrophils, which damage the tissue. Examples: lupus, post-streptococcal glomerulonephritis and serum sickness. Serum sickness follows a foreign protein, and the delay is the clue: about one to two weeks, while antibody is made. A related local version is the Arthus reaction, a painful, swollen patch at an injection site within hours, in someone who already has antibody.
2:15Type IV: T cell mediated, 48 to 72 hours
Type four is delayed, and it is T cell mediated, with no antibody needed. Memory T cells recognise antigen, release interferon gamma and other cytokines that activate macrophages, or cytotoxic T cells kill directly. It peaks at 48 to 72 hours. Examples: contact dermatitis, such as poison ivy, and the tuberculin skin test.
2:42The two neighbours sorted, and ACID
So our two neighbours: the bee sting is type one, and the poison ivy is type four. A memory aid is ACID: anaphylactic, cytotoxic, immune complex, delayed.
2:56Practice question
Your turn. A 41-year-old man is bitten by a snake and given an antivenom made from animal serum. Eleven days later he has fever, a urticarial rash and painful swollen joints. His serum C three concentration is low, and his urine has mild proteinuria. Which of the following is the most likely mechanism of his illness? A, cross-linking of IgE on mast cells. B, IgG against an antigen on cell surfaces, with complement lysis. C, deposition of antigen and antibody complexes, with complement activation. D, release of cytokines by antigen-specific T helper cells. E, direct killing of antigen-bearing cells by cytotoxic T cells. Pause here and decide.
3:46Pause, then the wrong options
A is out: IgE-mediated reactions start within seconds to minutes, not 11 days later. B is out: type two also uses complement, but it targets a fixed cell or tissue antigen, and nothing here points to one. D is out: T helper cytokine reactions peak at 2 to 3 days and do not use up C three. E is out: cytotoxic T cell killing is also type four, with no antibody and no complement consumption. So the answer is C.
4:22The answer: C, serum sickness
Fever, rash and joint pain about one to two weeks after a foreign protein, with low C three and proteinuria, is serum sickness: immune complexes and complement.
4:37Recap pocket card and next lesson
Three things to keep. One: type one is IgE on mast cells, within minutes; type two is antibody on cells; type three is immune complexes. Two: type four is T cell mediated and delayed, peaking at 48 to 72 hours. Three: timing is the clue. Type one takes minutes, serum sickness, a type three reaction to a first exposure, takes one to two weeks, and type four takes 2 to 3 days. Next, the immunodeficiencies: B-cell against T-cell defects.
Sources
Numbers in the text, e.g. [1], point here- Europe PMC, Clin Rev Allergy Immunol 2026, classification of hypersensitivity reactions: europepmc.org/article/PMC/PMC12946285
- Wikipedia, Hypersensitivity: en.wikipedia.org/wiki/Hypersensitivity
- Wikipedia, Serum sickness: en.wikipedia.org/wiki/Serum_sickness
- Europe PMC (serum sickness-like reactions; Arthus reaction): europepmc.org/article/PMC/PMC12564296 · europepmc.org/article/PMC/PMC7563237
- Europe PMC (Graves disease; myasthenia gravis): europepmc.org/article/PMC/PMC13574235 · europepmc.org/article/PMC/PMC13539138
Cells, receptors and complexes on screen are schematic and not to scale. The timing axis is typical timing on a log scale.
The practice question is original and its patient is synthetic. Every fact is checked against the sources above in independent accuracy reviews. Always follow your local guidelines and your own laboratory’s ranges.
Image credits. Illustrations: Servier Medical Art (smart.servier.com), CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/), adapted: man, lungs, skin, thyroid, synapse, kidney, joint, antibody, arm, syringe. NIAID NIH BioArt Source (bioart.niaid.nih.gov), public domain: bee, mast cell, peanut, red blood cell, macrophage, neutrophil, dendritic cell, T cell, apoptosis, B-cell receptor. Icons via bioicons.com, adapted: mast cell degranulation (Sebastian-Reinig, CC BY 4.0), leaf (Gina-Vong, CC0). Snake: Health Icons, CC0. The timing axis, antibodies, immune-complex lattices, receptor sketches, NK cell, question card, pocket card and all handwriting are drawn in code (original). No AI-generated anatomy, labels or graphs.
Corrections. None so far. Spotted an error? Email info@medservatory.com with the lesson code MS-S1-IMM-003.
For exam study only, not medical advice. Read the medical disclaimer.
In this series
Playlist on YouTube- EP 01MHC I vs MHC II: how antigen presentation works5:03
- EP 02T-cell activation: the two-signal model4:58
- EP 03Th1, Th2, Th17 and Treg: helper T-cell subsets5:13
- EP 04Antibody isotypes and class switching5:13
- EP 05Central vs peripheral tolerance: how lymphocytes learn self-tolerance5:26
- EP 06Complement system explained: three pathways, one ending5:24
- EP 07Complement deficiencies: C1q, C3, C5–C9 and C1 inhibitor5:15
- EP 08Hypersensitivity types I to IV: the four effectors5:20
- EP 09B-cell vs T-cell immunodeficiency: predict the infections5:24
- EP 10Hyper IgM syndrome: CD40 ligand and class switching5:19
- EP 11Chronic granulomatous disease: NADPH oxidase and the respiratory burst5:20
- EP 12Leukocyte adhesion deficiency: CD18 and neutrophil extravasation5:01
- EP 13Transplant rejection explained: hyperacute, acute, chronic and GVHD5:51
- EP 14Vaccine types explained: live, inactivated, conjugate and mRNA5:41