Mediators of Immediate Hypersensitivity

Slide 1 · Mediators of Immediate

Hypersensitivity

Mast-cell products, effector mechanisms, and tissue injury

From IgE receptor cross-linking to immediate and late-phase reactions

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning outcomes

Identify

Preformed granule contents

Newly generated lipid products

Secreted cytokines

Explain

Vascular leakage and edema

Bronchospasm and mucus

Leukocyte influx and injury

Integrate

Immediate reaction versus late phase

Eosinophil tissue damage

Allergic clinical phenotypes

Central question: How can one activated mast cell generate different clinical patterns?

Slide 3 · Type I hypersensitivity: The effector sequence

Allergen encounter

IgE-coated mast cell

Cross-linking of FcεRI

Mast-cell mediators

Tissue responses

Mediator identity determines the pattern and timing of injury.

Slide 4 · Sensitization precedes mast-cell mediator release

Environmental allergen stimulates a type 2 immune response.

IL-4 and IL-13 promote B-cell switching to IgE.

IgE binds high-affinity FcεRI on mast cells.

Th2 / Tfh cytokines

IgE-producing B cells

FcεRI-bound IgE

Sensitized mast cell

IgE coating prepares the mast cell for rapid reaction upon re-exposure.

Slide 5 · Antigen cross-linking initiates release

Multivalent allergen

Adjacent surface IgE linked

FcεRI receptors clustered

Intracellular activation

Mediator release

Cross-linking converts allergen recognition into effector activity.

Slide 6 · Why mast-cell location matters

Mast cells are concentrated near small blood vessels, nerves, and subepithelial tissues.

Released mediators act directly on vascular endothelium, glands, and smooth muscle.

Anatomical placement helps explain the rapid onset of local symptoms.

Subepithelial mast cell

Local mediator diffusion

Nearby vessels and glands

Edema and secretion

Local concentration and tissue proximity shape the visible reaction.

Slide 7 · Three concurrent activation programs

Activated mast cell

Granule discharge

Release preformed histamine, enzymes, proteoglycans

Membrane lipid metabolism

Generate leukotrienes and prostaglandins

Cytokine synthesis

Recruit and activate inflammatory leukocytes

One trigger launches rapid and sustained effector programs.

Slide 8 · Immediate and late-phase responses

After re-exposure to allergen

Within minutes

2–24 hours

Vasodilation, edema, mucus secretion and smooth-muscle spasm

Leukocyte infiltration, epithelial injury and sustained inflammation

A later inflammatory phase can persist without renewed antigen exposure.

Slide 9 · Mast-cell mediator families

Mediator family

Principal components

Dominant effect

Preformed granule

Histamine; Proteases; Proteoglycans

Rapid tissue responses; Storage / injury

Lipid products

Leukotrienes; Prostaglandin D₂

Bronchospasm, leakage, chemotaxis

Cytokines

TNF; IL-1; IL-4; Chemokines

Recruitment and Th2 amplification

Timing differs because some products are stored whereas others are synthesized.

Slide 10 · Preformed granules provide an immediate supply

Mast-cell granules contain biologically active products before re-exposure.

Receptor-induced degranulation expels these products into nearby tissue.

This rapid discharge precedes newly synthesized cytokine effects.

Mast-cell degranulation (schematic)

Histamine and

Granule products

Granule storage

Stored mediators explain why tissue changes can begin within minutes.

Slide 11 · Three categories of granule contents

Vasoactive amines

Histamine

Vascular permeability

Smooth-muscle and gland effects

Enzymes

Tryptase; Chymase

Acid hydrolases

Tissue injury / mediator generation

Proteoglycans

Heparin

Chondroitin sulfate

Packaging and storage of amines

All are preformed, but their functions are not interchangeable.

Slide 12 · Histamine is the dominant granule amine

Histamine is the most important mast cell–derived vasoactive amine.

It acts rapidly on local vascular, smooth-muscle, and glandular targets.

Its combined effects account for characteristic early allergic manifestations.

Mast-cell degranulation

Histamine release

Target-cell response

Immediate symptoms

Histamine links a molecular product to a rapid multisystem phenotype.

Slide 13 · Histamine increases vascular permeability

Histamine enhances vascular leakage from the microcirculation.

Extravasation of fluid produces local tissue edema.

Leakage contributes to swelling in immediate hypersensitivity.

Conceptual vessel wall and leakage

Vessel lumen

Interstitial fluid accumulation

Increased endothelial permeability

Edema is a functional consequence of mediator-driven vascular leakage.

Slide 14 · Histamine contracts smooth muscle

Histamine can induce intense smooth-muscle contraction.

Bronchial constriction contributes to narrowed airways.

Contraction provides a mechanistic basis for immediate respiratory symptoms.

Bronchial lumen (conceptual cross-sections)

Before contraction

After contraction

Schematic; Illustrates functional narrowing

Bronchospasm is not solely an inflammatory-cell infiltration effect.

Slide 15 · Histamine stimulates mucus secretion

Histamine stimulates glands in nasal, bronchial, and gastric mucosa.

Enhanced secretion accompanies other early tissue effects.

In the upper airway, mucus production helps explain rhinorrhea.

Histamine

Nasal / bronchial glands

Increased secretion

Mucosal symptoms

A single mediator can act on both the vascular and secretory compartments.

Slide 16 · Histamine acts on several tissue compartments

Blood vessels

Greater vascular permeability

Fluid movement into interstitium

Rapid edema

Smooth muscle and glands

Contraction contributes to airway narrowing

Glandular activation increases mucus

Symptoms vary with involved organ

The target tissue—not only the mediator—determines the phenotype.

Slide 17 · Mast-cell neutral proteases: Tryptase and chymase

Granule matrix contains neutral proteases, including tryptase and chymase.

Acid hydrolases are additional granule enzymes.

Proteolysis can produce damage beyond transient vascular leakage.

Mast-cell granule

Tryptase / chymase

Protein cleavage

Local tissue effects

Proteases represent a tissue-injury arm of mast-cell degranulation.

Slide 18 · Proteases can amplify soluble mediator generation

Granule proteases

Cleavage of precursor proteins

Kinins or complement components

Additional inflammatory effects

Kinin and complement generation as protease-associated effects.

Slide 19 · Complement fragments can reinforce mast-cell activation

Activated complement components may be generated by granule enzymes.

C3a and C5a can themselves act as mast-cell activators.

This gives complement and mast-cell pathways potential for reciprocal reinforcement.

Proteolytic activity

Activated complement

Mast-cell stimulation

Further mediator release

Complement activation is an additional trigger, not proof of IgE dependence.

Slide 20 · Proteoglycans organize the granule contents

Heparin and chondroitin sulfate are granule proteoglycans.

They help package and store bioactive amines.

Their major teaching role in this section is intragranular organization.

Proteoglycan matrix

Amine association

Concentrated storage

Ready discharge

Storage chemistry is part of the mechanism of rapid mediator release.

Slide 21 · Heparin and chondroitin sulfate

Heparin

A familiar anticoagulant molecule

Stored in mast-cell granules

Also contributes to granule packaging

Chondroitin sulfate

Granule-associated proteoglycan

Supports packaging and amine storage

Distinct from a vasoactive amine

Do not confuse granule storage constituents with the chief symptom-producing amine.

Slide 22 · Preformed mediator mechanisms compared

Component

Immediate function

Pathobiologic interpretation

Histamine

Permeability, contraction, mucus

Dominant early functional changes

Proteases

Protein cleavage and tissue damage

Can generate kinins / complement fragments

Proteoglycans

Amine packaging and storage

Permit high local granule concentration

Only histamine should be presented as the principal vasoactive amine.

Slide 23 · Lipid mediators are synthesized following activation

Unlike stored histamine, major lipid mediators derive from membrane phospholipids.

Mast-cell activation stimulates phospholipase A₂.

Arachidonic acid is the precursor for the major downstream products.

Membrane phospholipids

Phospholipase A₂

Arachidonic acid

Eicosanoid synthesis

Release of a precursor enables multiple distinct lipid mediator outputs.

Slide 24 · Phospholipase A₂ initiates eicosanoid synthesis

Mast-cell activation

Phospholipase A₂ activity

Arachidonic acid released

Enzyme-specific pathways

Membrane lipid metabolism is an independent response to FcεRI signaling.

Slide 25 · Arachidonic acid enters two principal pathways

Arachidonic acid

5-lipoxygenase

Produces leukotrienes B₄, C₄ and D₄

Cyclooxygenase

Produces prostaglandins, especially PGD₂

Different enzymes yield products with different dominant target effects.

Slide 26 · Cysteinyl leukotrienes produce strong tissue responses

Leukotrienes C₄ and D₄ are powerful vasoactive and spasmogenic agents.

They markedly increase vascular permeability.

They also produce pronounced bronchial smooth-muscle contraction.

5-lipoxygenase pathway

LTC₄ / LTD₄

Vascular leakage + bronchospasm

Immediate reaction

Cysteinyl leukotrienes contribute to edema and airway narrowing.

Slide 27 · Leukotriene potency is an important distinction

On a molar basis, LTC₄ and LTD₄ are several thousand times more active than histamine.

The comparison refers to vascular permeability and bronchial smooth-muscle contraction.

Potency is not equivalent to a claimed concentration or clinical effect size.

Equal molar comparison

Permeability + bronchial spasm

LTC₄ / LTD₄ far more potent than histamine

A strong molecular effect cannot be substituted for unreported patient-level measurements.

Slide 28 · Cysteinyl leukotrienes and bronchospasm

LTC₄ and LTD₄ directly support bronchial smooth-muscle contraction.

Narrowing of the airway lumen produces functional airflow obstruction.

This effect complements bronchospasm induced by histamine and PGD₂.

LTC₄ / LTD₄

Bronchial muscle contraction

Smaller airway caliber

Respiratory symptoms

Several mediator families converge on the bronchial smooth-muscle target.

Slide 29 · Cysteinyl leukotrienes and edema

LTC₄ and LTD₄ increase microvascular permeability.

Leakage of plasma-rich fluid creates local swelling.

The same lipid products can affect both vessels and airway smooth muscle.

LTC₄ / LTD₄

Increased leakage

Edematous mucosa

Reduced airway patency

Vascular leakage and bronchoconstriction can reinforce functional obstruction.

Slide 30 · Leukotriene B₄ is predominantly chemotactic

LTB₄ is highly chemotactic for neutrophils, eosinophils, and monocytes.

Its major emphasis is leukocyte recruitment rather than direct bronchospasm.

This links newly formed lipids to the cellular component of inflammation.

LTB₄

Chemotactic gradient

Leukocyte recruitment

Inflammatory amplification

Do not assign the same dominant function to every leukotriene.

Slide 31 · Leukotrienes: Functional division

LTB₄

Chemotaxis

Neutrophils

Eosinophils / monocytes

LTC₄

Vasoactive

Vascular leakage

Bronchial contraction

LTD₄

Spasmogenic

Airway smooth muscle

Increased permeability

Chemical family membership does not imply identical biological activity.

Slide 32 · Leukotriene mechanisms at a glance

Mediator

Primary targets

Key consequence

LTB₄

Circulating leukocytes

Chemotaxis and cell recruitment

LTC₄

Vasculature; Bronchial smooth muscle

Leakage and bronchospasm

LTD₄

Vasculature; Bronchial smooth muscle

Leakage and bronchospasm

LTB₄ and the cysteinyl leukotrienes occupy complementary roles.

Slide 33 · Prostaglandin D₂ arises from cyclooxygenase

PGD₂ is the most abundant prostaglandin produced by mast cells in this pathway.

Its production follows arachidonic acid metabolism by cyclooxygenase.

Its biological effects overlap with, but do not duplicate, leukotrienes.

Arachidonic acid

Cyclooxygenase

Prostaglandin D₂

Bronchial and glandular effects

PGD₂ is the central prostaglandin in this textbook discussion.

Slide 34 · PGD₂ is a potent bronchospastic mediator

PGD₂ causes intense bronchospasm.

It acts alongside histamine and LTC₄ / LTD₄ at the airway level.

Multiple chemical pathways converge on a single clinical effect.

PGD₂ release

Bronchial smooth muscle

Strong constriction

Airway obstruction

No one mediator explains every episode of bronchospasm.

Slide 35 · PGD₂ also increases mucus secretion

PGD₂ promotes increased mucus production.

The secretory effect accompanies bronchoconstriction.

Together, narrowing and secretion can intensify airway symptoms.

PGD₂

Airway mucosal glands

Mucus secretion

Luminal secretions

Airflow compromise may reflect both contraction and secretion.

Slide 36 · 5-lipoxygenase versus cyclooxygenase

5-lipoxygenase products

LTB₄: Leukocyte chemotaxis

LTC₄ and LTD₄: Leakage and spasm

Multiple functional leukotrienes

Cyclooxygenase product

PGD₂ is prominent in mast cells

Marked bronchospasm

Increased mucus secretion

Trace the enzyme before assigning a lipid mediator and its effect.

Slide 37 · Multiple lipids coordinate the immediate reaction

Leukotrienes and prostaglandins are synthesized following mast-cell activation.

Cysteinyl leukotrienes accentuate spasm and permeability.

PGD₂ adds bronchospasm and increased mucus secretion.

Mast-cell activation

Lipid pathway activation

Complementary effector products

Immediate tissue dysfunction

The mediator combination is functionally broader than any one product.

Slide 38 · Platelet-activating factor appears in the source scheme

The Robbins mast-cell mediator diagram also identifies platelet-activating factor (PAF).

The adjacent text develops the arachidonic acid–derived mediators in greater detail.

PAF is retained in the overall mediator inventory without assigning additional unverified effects.

Activated mast cell

Lipid mediator panel

PAF shown in Fig. 6.15

The figure establishes inclusion; It does not provide detailed PAF mechanisms here.

Slide 39 · Cytokines extend the reaction beyond degranulation

Activated mast cells synthesize and secrete cytokines and chemokines.

These products recruit other leukocytes to the affected tissue.

Their actions are central to the late-phase inflammatory response.

Mast-cell activation

Cytokines / chemokines

Leukocyte influx

Sustained inflammation

Cytokine signaling bridges the immediate and cellular phases.

Slide 40 · Mast-cell cytokine outputs

TNF and IL-1

Promote leukocyte recruitment

Support inflammatory infiltration

Contribute to the late phase

Chemokines

Guide leukocyte migration

Increase local infiltrates

Recruit additional effectors

IL-4

Amplifies type 2 immunity

Reinforces Th2 response

Sustains allergic bias

Different cytokines act on cell trafficking and immune-program amplification.

Slide 41 · TNF and IL-1 promote leukocyte recruitment

Mast cells can release TNF and IL-1 following activation.

These mediators are associated with leukocyte recruitment.

Recruited cells can provide an additional source of inflammatory cytokines.

TNF / IL-1

Inflammatory recruitment

New leukocyte influx

Secondary mediator release

A cytokine cascade can outlast the initial granule discharge.

Slide 42 · Chemokines give cellular recruitment direction

Chemokines attract specific leukocyte populations into affected tissue.

Their sources include mast cells and, later, other inflammatory cells.

Epithelial cells also add chemokines to the local environment.

Chemokine secretion

Leukocyte migration

Inflammatory infiltrate

Late-phase response

Recruitment is an organized molecular process, not random cell accumulation.

Slide 43 · IL-4 amplifies the type 2 immune response

Mast-cell–derived IL-4 can amplify ongoing Th2 responses.

Type 2 polarization sustains IgE-associated allergic inflammation.

The amplification mechanism is distinct from direct smooth-muscle contraction.

Mast-cell IL-4

Enhanced Th2 response

Further type 2 cytokines

Allergic amplification

IL-4 chiefly shapes immune programming rather than immediate edema.

Slide 44 · Recruited leukocytes become new mediator sources

Leukocytes drawn into tissue release additional cytokines and other inflammatory products.

The reaction can become self-sustaining after the initiating antigen exposure.

Late-phase injury therefore cannot be inferred from mast-cell contents alone.

Initial mast-cell signal

Recruited leukocytes

Additional mediator release

Persistent tissue inflammation

Later cellular contributors broaden the mediator repertoire.

Slide 45 · The epithelium actively shapes allergic inflammation

Epithelial cells are not passive bystanders during allergy.

They produce cytokines and chemokines that support recruitment.

Epithelial signals may promote Th2 differentiation.

Epithelial activation

Cytokines / chemokines

Type 2 immune reinforcement

Mucosal inflammation

The target organ becomes part of the inflammatory circuit.

Slide 46 · Three major tissue response modules

Mast-cell mediator release

Vascular

Vasodilation and increased leakage result in congestion / edema

Bronchial / glandular

Smooth-muscle spasm and mucus secretion

Inflammatory

Leukocyte influx and epithelial tissue injury

The clinical picture depends on which module predominates.

Slide 47 · The late phase can proceed without renewed exposure

The late reaction amplifies inflammation after the immediate event.

Further exposure to the original allergen is not required.

Activated and recruited leukocytes maintain the local response.

Initiating allergen event

Early mediator release

Leukocyte recruitment

Late inflammation

A persistent symptom need not represent a new allergen challenge.

Slide 48 · The two phases differ in timing and morphology

After re-exposure to allergen

Within minutes

2–24 hours

Rapid vasodilation, vascular congestion and edema

Eosinophils, neutrophils and T cells infiltrate the tissue

The late-phase response approximately 2–24 h after challenge.

Slide 49 · Immediate phase versus late-phase pathology

Immediate phase

Vascular and smooth-muscle abnormalities

Congestion, edema and secretion

Mast-cell amines / lipids dominate

Late phase

Inflammatory cell recruitment

Eosinophils, neutrophils and T cells

Cytokines / chemokines are prominent

Do not equate symptom onset and inflammatory tissue damage.

Slide 50 · Eosinophils are frequent late-phase effectors

Eosinophils are often abundant in late allergic lesions.

Recruitment depends on chemokines, including eotaxin.

These cells can directly injure epithelium when activated.

Eotaxin and chemokines

Eosinophil arrival

Eosinophil activation

Epithelial injury

Eosinophils convert cellular infiltration into tissue damage.

Slide 51 · Eotaxin recruits eosinophils to allergic tissue

Eotaxin is one of the chemokines attracting eosinophils.

Epithelial cells, Th2 cells, and mast cells can produce relevant chemokines.

Multiple source cells cooperate to concentrate eosinophils in tissue.

Epithelial / Th2 / mast cells

Eotaxin

Eosinophil recruitment

Allergic infiltrate

A chemotactic signal can be multicellular in origin.

Slide 52 · IL-5 activates eosinophils

IL-5 is a signature Th2 cytokine and a powerful eosinophil activator.

Activated eosinophils release products that injure surrounding tissue.

This provides a causal bridge from Th2 responses to epithelial damage.

Th2 cells

IL-5

Activated eosinophils

Tissue-damaging products

Recruitment and activation are distinct requirements for eosinophil injury.

Slide 53 · Eosinophil granule proteins damage epithelium

Activated eosinophils release major basic protein and eosinophil cationic protein.

Proteolytic enzymes contribute additional injury.

The combined products can injure epithelial surfaces in allergic disease.

Eosinophil-mediated epithelial injury

Granule proteins

Epithelial

Injury

Late-phase injury is mediated by infiltrating cells as well as soluble signals.

Slide 54 · Galectin-10 can form Charcot–Leyden crystals

Eosinophils contain abundant galectin-10.

After activation, this protein can crystallize into Charcot–Leyden crystals.

Following eosinophil lysis, extracellular crystals may be found in asthma sputum.

Eosinophil galectin-10

Protein crystallization

Eosinophil lysis

Extracellular crystals

Charcot–Leyden crystals are a consequence of eosinophil-associated inflammation.

Slide 55 · Charcot–Leyden crystals may amplify inflammation

The crystals can promote inflammatory activity.

They can enhance Th2-type responses.

Them as potential contributors to allergic reactions.

Galectin-10 crystals

Inflammatory stimulation

Enhanced type 2 response

Potential amplification

The source uses qualified language; A contributory role is not sole causation.

Slide 56 · Late-phase tissue injury becomes a feedback process

Mast-cell cytokines

Recruitment of leukocytes

Eosinophil mediator release

Epithelial damage

New epithelial signals

The recruited cells and epithelium can sustain the response.

Slide 57 · Allergic asthma prominently involves the late phase

The late-phase reaction is a major contributor to symptoms in some type I hypersensitivity disorders.

Allergic asthma is an important example.

Airway obstruction can reflect bronchospasm plus inflammatory tissue injury.

Immediate bronchospasm

Later eosinophilic inflammation

Epithelial injury

Sustained airway symptoms

An asthma phenotype cannot be understood from histamine alone.

Slide 58 · Allergic rhinitis is a useful immediate-phase example

Histamine stimulates nasal mucus secretion and promotes vascular leakage.

These effects explain rapid nasal symptoms after exposure.

The textbook contrasts antihistamine benefit in rhinitis with broader anti-inflammatory needs in asthma.

Allergen re-exposure

Rapid histamine effects

Nasal secretion + swelling

Rhinitis symptoms

The dominant effector phase influences the therapeutic mechanism.

Slide 59 · Systemic anaphylaxis reflects widespread effects

Robbins characterizes systemic anaphylaxis by vascular shock, widespread edema, and bronchospasm.

Diffuse vascular effects and airway constriction create a life-threatening syndrome.

This is a clinical extension of the same mediator mechanisms seen locally.

Systemic mediator release

Vascular and bronchial responses

Shock, edema and bronchospasm

Systemic anaphylaxis

Systemic distribution makes common mediator actions far more dangerous.

Slide 60 · Local versus systemic clinical manifestations

Local allergic reactions

Allergic rhinitis: Mucus and inflammation

Asthma: Muscle spasm and late injury

Urticaria: Localized skin reaction

Systemic anaphylaxis

Generalized vascular dysfunction

Widespread edema and airway effects

Potential circulatory collapse

Anatomical distribution is crucial in determining clinical severity.

Slide 61 · Why antihistamines do not address every phase

Antihistamines counter the actions of histamine.

Late-phase pathology involves cytokines, eosinophils, and epithelial injury.

Blocking one early amine does not eliminate these later mechanisms.

Histamine-dependent changes

Histamine blockade

Other pathways persist

Late inflammation may remain

Treatment targets must match the dominant pathological mechanism.

Slide 62 · Why anti-inflammatory treatment matters in asthma

Late-phase inflammatory injury in allergic asthma.

The text contrasts broad anti-inflammatory steroids with histamine-targeted treatment.

Mechanistically, suppressing inflammation addresses more than immediate amine effects.

Late leukocyte infiltration

Cytokines + eosinophil effects

Broad inflammation

Need for anti-inflammatory control

This is mechanistic teaching, not a patient-specific treatment protocol.

Slide 63 · Mediator–manifestation map

Clinical manifestation

Principal implicated mediators

Pathological explanation

Edema

Histamine; LTC₄ / LTD₄

Increased vascular permeability

Bronchospasm

Histamine; LTC₄ / LTD₄; PGD₂

Smooth-muscle contraction

Mucus secretion

Histamine; PGD₂

Glandular stimulation

Late tissue damage

TNF; IL-1; Chemokines; Eosinophil products

Cell recruitment and epithelial injury

A manifestation often has multiple convergent mediator pathways.

Slide 64 · Clinicopathologic application: Acute nasal symptoms

Shortly after allergen exposure, a sensitized person develops nasal secretion and mucosal swelling.

Interpretation

Which preformed mediator best explains rapid onset?

Which two tissue effects account for these symptoms?

Histamine → vascular leakage and increased mucus secretion.

Slide 65 · Clinicopathologic application: Persistent airway symptoms

An allergic airway reaction is followed hours later by continued symptoms with eosinophil-rich mucosal inflammation.

Interpretation

What phase of hypersensitivity is represented?

Which signals recruit and activate eosinophils?

Late phase → chemokines / eotaxin and IL-5.

Slide 66 · Clinicopathologic application: Mediator distinction

A newly synthesized leukotriene attracts neutrophils, eosinophils, and monocytes to the reaction site.

Interpretation

Identify the leukotriene.

Contrast its dominant effect with LTC₄ and LTD₄.

LTB₄ drives chemotaxis; LTC₄ / LTD₄ drive leakage and spasm.

Slide 67 · Integrated mechanism: From mediators to injury

Allergen-triggered mast cell

Stored products

Rapid histamine / protease discharge → early functional effects

Lipid synthesis

Leukotrienes and PGD₂ → permeability, spasm and mucus

Inflammatory signaling

Cytokines → recruitment → eosinophil / epithelial injury

The immediate and late responses arise from interconnected, distinct programs.

Slide 68 · High-yield distinctions for examination

Preformed versus newly synthesized

Histamine, enzymes, proteoglycans: Stored

Leukotrienes / PGD₂: Lipid-derived

Cytokines: Recruitment and amplification

Distinct lipid functions

LTB₄: Chemotaxis

LTC₄ / LTD₄: Permeability and spasm

PGD₂: Bronchospasm and mucus

Classify by origin, principal target, and timing—not by name alone.

Slide 69 · Three mechanistic take-home messages

Early phase

Histamine and lipids

Vascular changes

Airway and gland effects

Late phase

Cytokines and chemokines

Leukocyte influx

Eosinophil tissue damage

Clinical translation

Different target organs

Different mediator mixtures

Phase-specific therapeutic logic

A molecular inventory becomes useful only when linked to tissue consequences.

Slide 70 · Primary source and limits

Robbins, Cotran & Kumar: Pathologic Basis of Disease

11th edition (2026), Chapter 6: Diseases of the Immune System

Core section: Mediators of Immediate Hypersensitivity (p. 184)

Supporting context: mast-cell sensitization, late-phase reaction, and clinical examples (pp. 183–186)