type 1 and type 3 hyp3rsentivity reaction Robbins based md pathology exam answer

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Merck Manual type I type III hypersensitivity reactions immune complex

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Hypersensitivity Reactions: Type I and Type III

Robbins-based MD Pathology Exam Answer

Hypersensitivity reactions are exaggerated or inappropriate immune responses that cause tissue injury in a previously sensitized individual.

Feature	Type I	Type III
Other name	Immediate or anaphylactic hypersensitivity	Immune-complex-mediated hypersensitivity
Main immune mediator	IgE	IgG, sometimes IgM, immune complexes
Principal cells	Mast cells, basophils, eosinophils, Th2 cells	Neutrophils, complement, platelets
Time	Minutes after re-exposure	Usually hours to days
Key mechanism	Allergen cross-links mast cell-bound IgE	Circulating antigen-antibody complexes deposit in tissues
Examples	Anaphylaxis, allergic rhinitis, atopic asthma, urticaria	SLE, serum sickness, Arthus reaction, poststreptococcal glomerulonephritis

Type I Hypersensitivity

Definition

Type I or immediate hypersensitivity is a rapid reaction, usually occurring within minutes, following exposure to an allergen in an individual whose mast cells are coated with allergen-specific IgE.

It may be localized, such as allergic rhinitis, or systemic and fatal, as in anaphylaxis.
Robbins & Kumar Basic Pathology, p. 166.

Mechanism

1. Sensitization phase

On first exposure to allergen:

Allergen is taken up by antigen-presenting cells and presented to CD4+ T cells.
Naive CD4+ T cells differentiate into Th2 cells.
Th2 cells secrete:
- IL-4 and IL-13: stimulate B-cell class switching to IgE.
- IL-5: activates and recruits eosinophils.
Plasma cells produce allergen-specific IgE.
IgE binds by its Fc portion to high-affinity FcεRI receptors on mast cells and basophils.

The person is now sensitized but generally asymptomatic.

2. Activation phase on re-exposure

On subsequent exposure, the allergen cross-links adjacent IgE molecules fixed on mast cells. This causes mast-cell activation and degranulation.

3. Effector phase

A. Immediate reaction

Occurs within minutes and is due mainly to release of preformed mediators.

Preformed mediators

Histamine: vasodilation, increased vascular permeability, edema, bronchoconstriction, increased mucus secretion.
Proteases: tissue injury and activation of inflammatory pathways.
Eosinophil chemotactic factors.

Newly synthesized mediators

Leukotrienes C4, D4, E4: intense bronchospasm, vascular permeability, mucus secretion.
Prostaglandin D2: bronchospasm and vasodilation.
Platelet-activating factor.
Cytokines such as TNF, IL-4, IL-5, IL-13.

B. Late-phase reaction

Occurs about 2-24 hours later. It is caused by recruitment of:

Eosinophils
Neutrophils
Basophils
Th2 cells
Macrophages

These cells release cytokines, leukotrienes, proteases, and toxic granule proteins, leading to persistent inflammation and tissue injury.

Morphologic effects

Vasodilation and edema
Smooth-muscle contraction, especially bronchospasm
Increased mucus production
Eosinophil-rich inflammatory infiltrate
In chronic asthma: airway remodeling, smooth-muscle hypertrophy, goblet-cell hyperplasia, and mucus plugging

Examples

Systemic anaphylaxis due to drugs, insect stings, foods, or antiserum
Allergic rhinitis
Atopic bronchial asthma
Urticaria
Food allergy
Atopic dermatitis

Systemic anaphylaxis

Systemic mast-cell activation causes:

Hypotension and shock due to vasodilation and vascular leakage
Laryngeal edema
Severe bronchospasm
Urticaria and angioedema
Gastrointestinal cramps, vomiting, diarrhea

One-line summary:
Allergen + IgE-coated mast cells -> degranulation -> histamine and leukotrienes -> immediate vascular leak, bronchospasm, and mucus secretion.

Type III Hypersensitivity

Definition

Type III hypersensitivity is tissue injury caused by deposition of circulating antigen-antibody immune complexes, usually containing IgG, followed by complement activation and neutrophil-mediated inflammation.

Robbins, Cotran & Kumar Pathologic Basis of Disease, pp. 203-204.

Pathogenesis

1. Formation of immune complexes

Antigen combines with antibody, usually IgG, in the circulation.

Antigens may be:

Exogenous: microbial antigens, injected foreign proteins, drugs
Endogenous: self antigens in autoimmune disease, such as nuclear antigens in SLE

Small or medium-sized complexes formed in relative antigen excess are poorly cleared and are most likely to deposit in tissues.

2. Deposition of immune complexes

Complexes deposit preferentially in:

Walls of small blood vessels
Renal glomeruli
Synovium of joints
Skin
Serous membranes

Deposition is favored by high pressure, filtration of plasma, and turbulence in the circulation.

3. Inflammation and tissue injury

Deposited immune complexes activate complement.

C3a and C5a are anaphylatoxins, causing mast-cell degranulation and increased vascular permeability.
C5a is strongly chemotactic for neutrophils.
Neutrophils bind immune complexes through Fc receptors and complement receptors.
Frustrated phagocytosis causes release of lysosomal enzymes, reactive oxygen species, and inflammatory mediators into tissues.
This produces vasculitis, glomerulonephritis, arthritis, and tissue necrosis.

Morphology

Characteristic lesions include:

Acute necrotizing vasculitis
Fibrinoid necrosis of vessel walls
Neutrophilic infiltration and leukocytoclasia
Granular deposits of immunoglobulin and complement on immunofluorescence
In glomeruli: granular immune-complex deposition

Clinical forms

A. Systemic immune-complex disease: Serum sickness

This is the prototype of systemic type III hypersensitivity.

Cause: Exposure to large quantities of foreign protein, antiserum, some drugs, or microbial antigens.

Pathogenesis:

Antibodies form about one week after antigen exposure.
Antigen-antibody complexes form in circulation.
Complexes deposit in tissues.
Complement activation produces inflammation.

Clinical features:

Fever
Urticaria or rash
Arthralgia/arthritis
Lymphadenopathy
Proteinuria or nephritis
Vasculitis

B. Local immune-complex disease: Arthus reaction

The Arthus reaction is a localized type III reaction.

Mechanism: In a previously immunized person, local injection of antigen leads to formation of immune complexes at the injection site.

Features:

Local edema
Erythema
Hemorrhage
Neutrophilic vasculitis
Tissue necrosis in severe cases

It typically develops within several hours.

Examples of Type III Hypersensitivity

Systemic lupus erythematosus
Serum sickness
Arthus reaction
Poststreptococcal glomerulonephritis
Some forms of glomerulonephritis
Polyarteritis nodosa associated with hepatitis B antigen
Hypersensitivity pneumonitis
Rheumatoid arthritis, in part

Robbins lists SLE, serum sickness, Arthus reaction, and some forms of glomerulonephritis as prototypical type III disorders. Robbins & Kumar Basic Pathology, p. 166. A clinical reference overview likewise describes type III injury as inflammation due to deposited circulating immune complexes.

One-line summary:
Antigen-antibody complexes deposit in vessels, kidneys, or joints -> complement activation -> neutrophil recruitment -> vasculitis and tissue injury.

Key Differences for Viva

Point	Type I	Type III
Antibody	IgE	IgG or IgM
Antigen location	Binds IgE on mast-cell surface	Forms soluble immune complexes in circulation or in situ
Major cells	Mast cells, basophils, eosinophils	Neutrophils
Complement role	Not central	Central, especially C3a and C5a
Main lesion	Edema, bronchospasm, mucus hypersecretion	Vasculitis, fibrinoid necrosis, glomerulonephritis
Classic example	Anaphylaxis	Serum sickness
Local example	Urticaria	Arthus reaction

Exam conclusion

Type I hypersensitivity is an IgE-mediated immediate reaction due to mast-cell degranulation. Type III hypersensitivity is an immune-complex-mediated reaction in which deposited antigen-IgG complexes activate complement and recruit neutrophils, producing vasculitis and inflammatory tissue injury.

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