Biochemistry of Allergy and the Impact on Health

 

Biochemistry of Allergy and the Impact on Health

Allergies are exaggerated immune responses to normally harmless substances (allergens). The biochemical pathways underlying allergies involve immune sensitization, IgE production, mast cell activation, and inflammatory mediator release. These reactions can range from mild symptoms to life-threatening anaphylaxis. Understanding the biochemical basis helps in better diagnosis, prevention, and therapeutic intervention.

1. What Is an Allergy? 

An allergy is a hypersensitivity reaction mediated predominantly by Immunoglobulin E (IgE). When allergens such as pollen, dust mites, foods, or drugs enter the body, immune cells mistakenly identify them as threats and activate pathways involving:

• B cells
• T helper 2 (Th2) cells
• IgE antibodies
• Mast cells & basophils
• Histamine and other mediators

2. Sensitization Phase: How the Body First Develops an Allergy

Step-by-step Biochemical Events

1. Allergen Entry:
   Allergen particles (proteins, glycoproteins) are taken up by Antigen-Presenting Cells (APCs).
2. Activation of Th2 Cells:
   APCs present allergen fragments via MHC-II, stimulating Th2 cell differentiation.
3. Cytokine Release (Key Biochemical Events):
   Th2 cells release:
• IL-4 → promotes B cell class switching to IgE
• IL-5 → activates eosinophils
• IL-13 → enhances mucus secretion and IgE synthesis
4. IgE Production:
   B cells undergo class-switch recombination to produce IgE antibodies.
5. Binding to Mast Cells:
   IgE binds to FcεRI receptors on mast cells and basophils → the body is now “sensitized”.

No symptoms appear at this stage.

3. Re-Exposure Phase: The Actual Allergic Reaction

When the same allergen enters again:

1. Allergen binds to IgE on mast cells

→ Cross-linking of IgE–FcεRI complexes

2. Mast Cell Degranulation

Biochemical mediators released:

Immediate Response Mediators (within seconds)

• Histamine — vasodilation, itching, bronchoconstriction
• Tryptase & Chymase — tissue remodeling, inflammation
• Heparin — anticoagulant

Late Phase Mediators (minutes to hours)

Produced via enzymatic cascades:

• Leukotrienes (LTC4, LTD4, LTE4) via 5-lipoxygenase
• Prostaglandins (PGD2) via cyclooxygenase pathway
• Platelet-activating factor (PAF)

3. Cytokine & Chemokine Release

• TNF-α → recruits neutrophils
• IL-5 → eosinophil activation
• IL-4 / IL-13 → amplify IgE response

 

4. Major Biochemical Mediators and Their Effects

Mediator	Source	Biochemical Effect	Symptoms
Histamine	Mast cells	↑Vascular permeability, smooth muscle contraction	Sneezing, itching, swelling
Leukotrienes	Mast cells	Strong bronchoconstrictors	Asthma, wheezing
Prostaglandins	Mast cells	Vasodilation	Redness, pain
Tryptase	Mast cells	Tissue damage, biomarker	Anaphylaxis marker
IgE	B cells	Allergen-specific binding	Key antibody in allergy

 

5. Types of Allergic Conditions (Biochemistry Basis)

1. Allergic Rhinitis (Hay Fever)

• High levels of histamine and IL-4
• Nasal mucosa inflammation

2. Asthma (IgE-Mediated)

• Leukotrienes cause bronchoconstriction
• Goblet cell hyperplasia → excess mucus
• Chronic eosinophil-driven inflammation

3. Food Allergies

• Allergen proteins resist digestion → reach immune system intact
• GI mast cell activation → cramps, vomiting, anaphylaxis

4. Anaphylaxis

• Systemic release of histamine and leukotrienes
• Rapid drop in blood pressure (vasodilation)
• Requires immediate epinephrine intervention

 

6. Allergy Biochemistry: Why Is It Increasing?

1. Hygiene Hypothesis

Reduced microbial exposure ↔ increased Th2 skewing.

2. Climate Change

• Higher pollen loads
• Longer flowering seasons
• Formation of “super allergens”

3. Urban Lifestyle

• Indoor pollution, microplastics, particulate matter
• Decreased vitamin D (immune imbalance)

4. Dietary Factors

• Reduced consumption of omega-3 fatty acids
• Increased processed foods → inflammation

7. Diagnostic Biomarkers (Biochemistry)

1. Serum IgE Levels

Total and allergen-specific (ELISA)

2. Tryptase Levels

Elevated during anaphylaxis

3. Eosinophil Counts

Chronic allergic inflammation

4. Skin Prick Test

Measures mast cell reactivity

 

8. Treatments Based on Biochemistry

1. Antihistamines

Block H1 receptors → reduce itching, sneezing.

2. Corticosteroids

Inhibit inflammatory cytokines: IL-4, IL-5, TNF-α

3. Leukotriene Inhibitors

Montelukast blocks leukotriene receptors.

4. Mast Cell Stabilizers

Cromolyn sodium prevents degranulation.

5. Immunotherapy (Desensitization)

Gradual exposure reduces IgE and increases IgG4 (“blocking antibodies”).

6. Biological Drugs

• Omalizumab → anti-IgE monoclonal antibody
• Dupilumab → blocks IL-4/IL-13 pathways

9. Impact of Allergies on Health

Physical Health

• Chronic inflammation → asthma, sinusitis, dermatitis
• Sleep disruption due to nasal congestion
• Increased risk of respiratory infections

Mental Health

• Anxiety from unpredictable flare-ups
• Cognitive fatigue from chronic inflammation

Economic Burden

• Medication costs
• Lost productivity
• Increased hospital visits during allergy seasons

10. Summary

• Allergies are IgE-mediated hypersensitivity reactions.
• Main cells: mast cells, basophils, eosinophils.
• Main mediators: histamine, leukotrienes, prostaglandins.
• Key cytokines: IL-4, IL-5, IL-13 (Th2 profile).
• Impact ranges from mild symptoms to life-threatening anaphylaxis.
• Rising globally due to lifestyle, pollution, and climate factors.
• Treatment targets biochemical pathways to reduce inflammation.