Allergies: When Your Immune System Overreacts

An Immune System Gone Wrong

Allergies are fundamentally a case of mistaken identity. Your immune system evolved to detect and destroy dangerous invaders like bacteria, viruses, and parasites. But in allergic individuals, it sometimes identifies harmless substances as threats, mounting an inflammatory response entirely out of proportion to any actual danger.[1]

The substances that trigger allergies are called allergens. They're typically proteins found in:

• Pollen from trees, grasses, and weeds
• Dust mites and their droppings
• Pet dander (skin flakes), saliva, and urine
• Foods: peanuts, tree nuts, shellfish, milk, eggs, wheat, soy, fish
• Insect venoms (bees, wasps, fire ants)
• Medications (penicillin, NSAIDs, others)
• Latex and other materials

What makes these particular proteins allergenic while countless other foreign proteins are ignored? The answer involves a complex interplay of genetics, timing of exposure, and immune system quirks that scientists are still unraveling.

The Immunology of Allergic Reactions

Allergic reactions involve a specific arm of the immune system and unfold in two phases: sensitization and reaction.

Phase 1: Sensitization

The first time you encounter an allergen, nothing obvious happens. But your immune system is taking notes:

1. Antigen presentation: Dendritic cells capture the allergen and present it to T helper cells
2. Th2 polarization: In allergic individuals, T cells differentiate into Th2 cells rather than other T helper subtypes
3. B cell activation: Th2 cells release cytokines (IL-4, IL-13) that instruct B cells to produce IgE antibodies specific to the allergen
4. Mast cell arming: IgE antibodies bind to receptors on mast cells in tissues and basophils in blood, "arming" them for future encounters

Why do some people's immune systems take the Th2 path while others don't? Genetics plays a major role. People with atopy, a hereditary tendency toward allergic conditions, have immune systems that are biased toward Th2 responses. If one parent has allergies, their child has about a 30-50% chance of developing them. If both parents are allergic, the risk rises to 60-80%.

You're now sensitized. The trap is set.

Phase 2: The Allergic Reaction

On subsequent exposure, the allergen binds to IgE antibodies already attached to mast cells. When an allergen crosslinks two or more IgE molecules, it triggers degranulation, causing the mast cell to explosively release its contents:[2]

This cascade produces the familiar symptoms: sneezing, itching, hives, swelling, wheezing. In severe cases, it causes anaphylaxis, a systemic reaction with dangerous drops in blood pressure and airway constriction.

Why Does This System Exist?

The IgE-mast cell system seems like a design flaw, but it evolved for good reason: defense against parasites. Parasitic worms (helminths) were ubiquitous throughout human evolution, and IgE-mediated responses help expel them through increased mucus production, smooth muscle contraction, and recruitment of eosinophils.[3]

In developed countries, improved sanitation has largely eliminated parasitic infections. The hygiene hypothesis proposes that without parasites to fight, this arm of the immune system misfires against harmless environmental proteins instead. Supporting this theory: allergies are far more common in urban, industrialized populations than in rural communities with higher rates of parasitic infection. Children raised on farms, exposed to diverse microbes and livestock, have significantly lower allergy rates than their urban counterparts.

"We evolved with parasites. Our immune system expects them. In their absence, it finds new targets and attacks our food, our pets, the spring air."

Adult-Onset Allergies: It Can Happen to Anyone

Many people assume allergies are something you either have from childhood or don't have at all. This is incorrect. Allergies can develop at any age, and adult-onset allergies are surprisingly common.[4]

Recent studies suggest that nearly half of adults with food allergies developed at least one of them in adulthood. Shellfish allergy, in particular, frequently appears for the first time in adults.

Why Do Adult-Onset Allergies Happen?

Several factors can trigger new allergies later in life:

• Relocation: Moving to a new environment exposes you to different pollens and allergens. Many people develop hay fever after moving to a new region.
• Changes in exposure: Getting a pet for the first time, changing jobs (occupational exposures), or dietary changes can introduce new allergens.
• Immune system changes: Pregnancy, illness, or aging can alter immune function and tolerance.
• Cumulative exposure: Sometimes sensitization builds gradually over years of low-level exposure before crossing a threshold.
• Cross-reactivity: Existing allergies can expand because IgE antibodies sometimes recognize proteins that are structurally similar to the original allergen. Birch pollen allergy, for instance, can lead to oral allergy syndrome with apples, cherries, and other fruits because these foods contain proteins that resemble birch pollen proteins closely enough to trigger the same IgE antibodies.
• Loss of tolerance: Immunological tolerance is an active process that requires ongoing exposure to maintain. If you avoid a food for a long time (intentionally or not), the regulatory mechanisms that were keeping your immune system calm may fade, and you can become allergic upon re-exposure.

The Allergic March

In children, allergies often follow a predictable progression called the atopic march:

1. Eczema (atopic dermatitis): Often appears first in infancy
2. Food allergies: Develop in early childhood
3. Asthma: Emerges in later childhood
4. Allergic rhinitis (hay fever): Often the last to appear

Not everyone follows this pattern, and many outgrow childhood allergies (especially milk and egg). But the atopic march illustrates how allergic tendencies can evolve over a lifetime.

Anaphylaxis: The Life-Threatening Reaction

Anaphylaxis is a severe, potentially fatal systemic allergic reaction. It occurs when massive mast cell degranulation affects multiple organ systems simultaneously:[5]

• Cardiovascular: Vasodilation and fluid leakage cause dangerous hypotension (anaphylactic shock)
• Respiratory: Bronchospasm and laryngeal edema can obstruct the airway
• Skin: Widespread hives, flushing, angioedema
• GI: Nausea, vomiting, abdominal pain, diarrhea

Anaphylaxis requires immediate treatment with epinephrine (adrenaline), which reverses bronchoconstriction, supports blood pressure, and inhibits further mediator release. People with known anaphylaxis risk should carry epinephrine auto-injectors (EpiPen) at all times.

Treatment Approaches

Avoidance

The most effective strategy for food and drug allergies is strict avoidance. For environmental allergies, reducing exposure helps: air purifiers, dust mite covers, keeping windows closed during high pollen days.

Medications

• Antihistamines: Block histamine receptors; relieve sneezing, itching, hives
• Corticosteroids: Nasal sprays for rhinitis, creams for skin, systemic for severe reactions
• Decongestants: Relieve nasal congestion (short-term use)
• Leukotriene inhibitors: Block leukotriene effects (montelukast)
• Mast cell stabilizers: Prevent degranulation (cromolyn)
• Epinephrine: Emergency treatment for anaphylaxis

Immunotherapy

Allergen immunotherapy can actually modify the underlying disease by inducing tolerance. Gradually increasing doses of allergen shift the immune response away from IgE-mediated reactions. Over time, the immune system produces more IgG4 antibodies (which block allergens without triggering symptoms) and generates regulatory T cells that actively suppress the allergic response. The result is a genuine change in immune behavior, not just symptom relief:

• Subcutaneous immunotherapy (SCIT): Traditional "allergy shots" given over 3-5 years
• Sublingual immunotherapy (SLIT): Tablets or drops placed under the tongue daily
• Oral immunotherapy (OIT): For food allergies, gradually increasing oral doses (peanut OIT now FDA-approved)

Immunotherapy requires commitment. SCIT involves weekly injections for months, then monthly maintenance shots for years. But for many patients, the benefits persist long after treatment ends, suggesting true immune reprogramming rather than temporary suppression.

Biologics

Newer medications target specific immune pathways:

• Omalizumab (Xolair): Anti-IgE antibody; binds free IgE before it can arm mast cells
• Dupilumab (Dupixent): Blocks IL-4/IL-13 signaling; approved for severe eczema, asthma, and nasal polyps

Prevention: Early Exposure May Help

The thinking on food allergy prevention has shifted dramatically. The old advice to avoid allergenic foods in infancy was wrong and may have increased allergy rates.

The landmark LEAP study showed that early introduction of peanuts to high-risk infants reduced peanut allergy by 81%.[6] Current guidelines now recommend introducing peanut-containing foods around 4-6 months for high-risk infants (those with severe eczema or egg allergy).

The principle: early exposure during a critical window may promote tolerance rather than sensitization. Avoiding allergens may paradoxically increase risk.

The Rise of Allergies

Allergic diseases have increased dramatically in developed countries over the past 50 years, too fast for genetic change. Proposed explanations include:

• Hygiene hypothesis: Reduced infections and parasite exposure
• Microbiome changes: Altered gut bacteria from antibiotics, processed food, C-sections
• Vitamin D deficiency: Less time outdoors
• Delayed allergen introduction: Well-meaning avoidance strategies backfired
• Environmental changes: Climate change extending pollen seasons, air pollution

Allergies represent a mismatch between our evolved immune system and our modern environment. Understanding the immunology opens doors to better treatments and perhaps eventually, prevention of this increasingly common condition.