Describe the role of eosinophils in control of allergy reactions.

Eosinophil Development and Activation

Eosinophils originate in the bone marrow and undergo maturation under the influence of several cytokines, most notably Interleukin-5 (IL-5). IL-5 is primarily produced by Th2 cells, a subset of T helper cells that are central to the allergic immune response. Upon allergen exposure, antigen-presenting cells (APCs) activate Th2 cells, leading to IL-5 production and subsequent eosinophil differentiation and recruitment.

Role in Allergic Reactions: A Step-by-Step Process

1. Sensitization Phase: Initial exposure to an allergen leads to the production of allergen-specific IgE antibodies by B cells. These IgE antibodies bind to high-affinity FcεRI receptors on mast cells and basophils.
2. Early Phase Reaction: Subsequent exposure to the same allergen cross-links the IgE antibodies on mast cells and basophils, triggering degranulation and the release of histamine, leukotrienes, and prostaglandins. This results in vasodilation, increased vascular permeability, and smooth muscle contraction – the hallmark symptoms of an immediate allergic reaction.
3. Late Phase Reaction: This phase, occurring 4-8 hours after allergen exposure, is where eosinophils become prominent. Several factors contribute to eosinophil recruitment:
   • Cytokine Production: Mast cells and Th2 cells release cytokines like eotaxin (CCL11), eotaxin-2 (CCL24), and eotaxin-3 (CCL25), which act as chemoattractants for eosinophils, guiding them to the site of inflammation.
   • Adhesion Molecule Expression: Endothelial cells upregulate adhesion molecules like VCAM-1 and ICAM-1, facilitating eosinophil adhesion and extravasation.

Eosinophil Effector Functions in Allergy

Once recruited to the site of allergic inflammation, eosinophils exert their effects through several mechanisms:

• Granule Protein Release: Eosinophil granules contain a variety of cytotoxic proteins, including:
  • Major Basic Protein (MBP): Toxic to epithelial cells and contributes to airway hyperreactivity in asthma.
  • Eosinophil Cationic Protein (ECP): Damages tissues and contributes to inflammation.
  • Eosinophil Peroxidase (EPO): Generates reactive oxygen species (ROS) and contributes to oxidative stress.
  • Neurotoxin: Causes neuronal damage.
• Cytokine and Chemokine Production: Eosinophils produce cytokines like IL-4, IL-5, IL-13, and chemokines that amplify the allergic response and recruit other inflammatory cells.
• Leukotriene Synthesis: Eosinophils can synthesize leukotrienes, potent mediators of inflammation that contribute to bronchoconstriction and mucus production.
• Platelet-Activating Factor (PAF): Eosinophils release PAF, contributing to vasodilation and bronchoconstriction.

Eosinophils in Specific Allergic Diseases

Disease	Eosinophil Role
Asthma	Eosinophilic inflammation in the airways contributes to airway hyperreactivity, mucus production, and airflow obstruction.
Allergic Rhinitis	Eosinophils infiltrate the nasal mucosa, causing inflammation, congestion, and sneezing.
Atopic Dermatitis	Eosinophils contribute to skin inflammation, itching, and eczema.
Hypereosinophilic Syndrome (HES)	A rare disorder characterized by persistently elevated eosinophil counts and organ damage. While not always allergic, some forms are associated with allergic triggers.

While traditionally viewed as pro-inflammatory, recent research suggests eosinophils can also exhibit regulatory functions, potentially contributing to the resolution of allergic inflammation under certain conditions. This highlights the complex and context-dependent role of eosinophils in allergic diseases.