This document categorizes four types of hypersensitivity reactions: Type I is IgE-mediated immediate reactions, Type II is antibody-mediated cytotoxic reactions, Type III involves immune complex-mediated reactions, and Type IV is cell-mediated delayed hypersensitivity. Each type has distinct etiology, symptoms, and treatment approaches, detailing conditions such as anaphylaxis, autoimmune diseases, and chronic inflammatory responses. Treatments vary from antihistamines and corticosteroids to immunosuppressants depending on the reaction severity.

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Types of hypersensitivity reaction
Types Of
Hypersensitivity
Reaction

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 Type I - IgE mediated immediate reaction
 Type II- Antibody-mediated cytotoxic reaction
(IgG or IgM antibodies)
 Type III- Immune complex-mediated reaction
 Type IV- Cell-mediated, delayed hypersensitivity
reaction
Introduction

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● Depending upon the rapidity, duration and
type of the immune response, these 4 types
of hypersensitivity reactions are grouped
into :
i) Immediate type
ii) Delayed type

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● Type I hypersensitivities include atopic diseases, which are
an exaggerated IgE mediated immune responses (i.e.,
allergic: asthma), and allergic diseases, which are immune
responses to foreign allergens (i.e., anaphylaxis).
● The allergens that result in a type I hypersensitivity may be
harmless (i.e., pollen, mites, etc.) or more hazardous such
as insect venoms.
Type I Anaphylactic Reaction

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Type I Anaphylactic REACTION
Etiology
&
Pathogenesis
Signs
&
symptoms
Examples of
reaction type
Treatment

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 Type I hypersensitivity occurs as a result of exposure
to an antigen. The response to the antigen occurs
in two stages: the sensitization and the effect stage.
 In the sensitization stage, the host experiences an
asymptomatic contact with the antigen.
 In the "effect" period, the pre-sensitized host is re-
introduced to the antigen, which then leads to a type I
anaphylactic or atopic immune response .
Etiology & Pathogenesis

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Range from mild, local (e.g.
urticaria. rhinorrhea, itching) to
life-threatening anaphylactic
reaction (e.g. cardiac
arrhythmia, shock,
bronchospasm, laryngeal
obstruction) .
SIGNS & SYMPTOMS

11. Examples
Common Type I Hypersensitivity Reactions :-
 Ingested allergens
• Foods, dander, bee stings, mold, drugs , pollen .
 Other allergens :-
• Latex, lotions, soaps, penicillin
 Atopic eczema
 Allergic urticarial
 Allergic rhinitis
Allergic asthma
 Anaphylaxis
 Eosinophilic esophagitis

12. Medications :-
 Symptom-based
● Antihistamines (e.g. H1 blockers),
corticosteroids , epinephrine .
 Other interventions
● Hypo /de-sensitization
Escalating doses of allergen
subcutaneously injected over course
of years.
Treatment

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Type II hypersensitivity reaction refers to an antibody-
mediated immune reaction in which antibodies (IgG or IgM)
are directed against cellular or extracellular matrix antigens
with the resultant cellular destruction, functional loss, or
damage to tissues.
TYPE II Cytotoxic Reaction

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Type II: Cytotoxic (Cytolytic) reaction

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TYPE II Cytotoxic reaction
Signs
&
symptoms
Examples of
reaction type II
Treatment
Etiology
&
Pathology

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 The type II hypersensitivity immune reaction develops
in response to modifications of cell surface or matrix-
associated antigens generating antigenic epitopes that are
regarded as foreign by the immune system.
 The most common causes include medications like
penicillin, thiazides, cephalosporin , and methyldopa.
 The drug molecule either binds to the surface of cells
resulting in a neoantigen or alter the epitopes of the
existing self-antigen on the cell surface.
Etiology

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● In type II hypersensitivity, following exposure to the
inciting agent, autoantibodies are produced (IgG & IgM)
to the host cells (sensitization phase), promoting a series of
pathogenic outcomes (effector phase).
● The pathophysiology of type II hypersensitivity
reactions can be broadly classified into three types :-
1. Cell depletion or destruction without inflammation.
2. Inflammation mediated by complement or Fc receptor.
3. Cellular dysfunction by antibodies.
Pathology

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 Acute hemolytic transfusion reactions
 Fevers , chills nausea, vomiting , flank
 tachycardia
 chest pain , dyspnea
 Tremor, insomnia, irritability, weight loss
 Fatigue , jaundice , hepatosplenomegaly (HSM)
 Bullous pemphigoid
Signs & Symptoms

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● Hemolytic disease of the newborn
● Autoimmune hemolytic anemia C
● Immune thrombocytopenic
● Rheumatic fever
● Goodpasture syndrome
● Guillain-Barré syndrome
● Graves' disease
Common Type II hypersensitivity reactions

21. Medications
• Corticosteroids
 Severe reactions
may require :-
• plasmapheresis
• immunosuppressant
Treatment

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An abnormal immune response is mediated by the formation
of antigen-antibody aggregates called "immune complexes.“
They can precipitate in various tissues and trigger the
classical complement pathway.
Complement activation leads to the recruitment
of inflammatory cells that release lysosomal enzymes and free
radicals at the site of immune complexes, causing tissue
damage.
Type III Hypersensitivity Reaction
Immune complex-mediated reaction

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The principle feature that
separates type III reactions from
other hypersensitivity reactions
is that in type III the antigen-
antibody complexes are pre-
formed in the circulation before
their deposition in tissues .

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Type III Hypersensitivity Reaction
Etiology
&
Pathology
Signs
&
Symptoms
Examples of
reaction type III
Treatment

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Etiology & Pathology

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If triggered by single exposure to antigen , resolves after
catabolism of immune complexes acute serum sickness .
If repeated/prolonged exposure chronic serum sickness .
Common sites of immune complex :-
● accumulation
● Blood vessel walls vasculitis
● Kidneys glomerulonephritis
● Joints arthritis

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● Serum Sickness
● Post-streptococcal Glomerulonephritis
● Systemic Lupus Erythematosus
● Farmers' Lung (Hypersensitivity Pneumonitis)
● Rheumatoid Arthritis
Common Type Ill hypersensitivity
reactions :-

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● Fever, fatigue, weight loss .
● Skin : rash , urticaria
● Kidney : proteinuria
● Joints : arthralgias
● Mucosa : ulcers
● Serosa : pleuritis, pericarditis
Signs & symptoms

30. Treatment
Medications
• Systemic lupus erythematosus
(SLE) :-
Administration of anti- inflammatory,
corticosteroids, cytotoxic medications
to decrease inflammatory activity.

31. Type IV hypersensitivity reaction
 Type IV hypersensitivity typically occurs at least 48 hours after
exposure to an antigen. It involves activated T cells, which release
cytokines and chemokines, and macrophages and cytotoxic CD8+ T
cells that are attracted by these moieties.
 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.

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Etiology
&
Pathology
Signs
&
symptoms
Examples of
reaction type II
Treatment
Type IV Hypersensitivity Reaction

34. Etiology & Pathology
Type IV hypersensitivity reaction are, to some extent, normal
physiological events that aid in the fight against infections, and
disruption in this system can predispose to a variety of opportunistic
illnesses.
• Exposure to poison ivy resulting in contact dermatitis is a
classic example.
• Several drugs (antibiotics, anticonvulsants) can
trigger type IV hypersensitivity reactions .Certain viral infections,
when exposed to certain drugs, can trigger a reaction, such as
cytomegalovirus with antibiotics, Epstein Barr virus with
amoxicillin.

36. There are three subtypes of Type IV
hypersensitivity:
 Contact Dermatitis
 Tuberculin-type Hypersensitivity
 Granulomatous-type Hypersensitivity

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Contact hypersensitivity dermatitis
occurs when haptens, which are considered as exogenous
antigens, penetrate the skin with proximity to epidermal and
dermal cells resulting in an inflammatory reaction.
Additionally, keratinocytes help in recruiting immune cells by secreting
other groups of cytokines .
This results in inflammation of the skin with
swelling, itchiness, and pain.

38. Tuberculin-type hypersensitivity
can be seen after intradermal
injection of purified protein
derivative (PPD) called tuberculin
(product of tuberculosis bacillus),
that produces measurable local
induration and swelling, typically
measured in millimeters between
48 to 72 hours after the injection.
This local reaction indicates the
presence of type four
hypersensitivity. The tuberculin
test is a validated method to
diagnose tuberculosis infection,
even if latent.

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● Can occur in response to a variety of antigens.
Macrophages that engulfed antigens are unable to destroy
them and recruit several more macrophages to the site of these
antigens. A collection of macrophages filled with intracellular
antigens is termed granuloma. One instance is sarcoidosis
disease, which is a systemic granulomatous disease of unknown
cause, with a wide variety of clinical presentations.
Granulomatous-type Hypersensitivity

40. Signs & symptoms
 Local inflammatory reaction :-
• erythema
• warmth
• edema
• fever
 Sequelae of organ-specific cell destruction Islet cell destruction in
pancreas →insulin-deficient (e.g. lethargy, seizure, coma) .
 Chronic inflammation granuloma
 formation organ failure (e.g. lethargy, seizure, coma) Chronic inflammation granuloma formation organ failure

41. • Graft-versus-host disease (GVHD).
• Mantoux test
• Allergic contact dermatitis
• Multiple sclerosis
• Coeliac disease.
• Giant-cell arteritis
• Postorgasmic illness syndrome
• Diabetes mellitus type 1 Hashimoto's
thyroiditis
Common Type IV hypersensitivity reactions :-

42. Medications
• Corticosteroids for inflammatory
control Systemic for severe,
generalized reactions.
• site-specific (e.g. topical for
contact dermatitis; inhaled for
hypersensitivity pneumonitis).
Treatment

43. Summary in video

44. References
 Justiz VaillaAA, Vashisht R, Zito PM. Immediate Hypersensitivity Reactions.
[Updated 2021 Nov 15]. In: StatPearls [Internet]. Treasure Island (FL):
StatPearls Publishing; 2022 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK513315/
 https://www.osmosis.org/
 Marwa K, Kondamudi NP. Type IV Hypersensitivity Reaction. [Updated 2021
Nov 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing;
2022 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK562228/

45. References
 Bajwa SF, Mohammed RHA. Type II Hypersensitivity Reaction. [Updated
2021 Sep 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls
Publishing; 2022 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK563264
 Usman N, Annamaraju P. Type III Hypersensitivity Reaction. [Updated 2021
Aug 22]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing;
2022 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK559122/
 Essential Pathology For Dental Students ; Authors, Harsh Mohan,
Sugandha Mohan ; Edition, illustrated ; Publisher, JP Medical Ltd, 2011.