Immunological aspects of allergy and anaphylaxis part 34

ALLERGIC DISEASE OF THE RESPIRATORY TRACT

The nature of the respiratory process involves inhalation of airborne allergens. As a result, the components  of the respiratory tract, including the nose, sinuses, and lungs, are disproportionately affected by allergic disease. In clinical practice, the common manifestations include seasonal or perennial allergic rhinitis, allergic sinusitis, and allergic asthma. The former two are often described together as allergic rhinosinusitis. Although clinically distinct, each condition involves similar underlying immunologic processes.

Immunological aspects of allergy and anaphylaxis part 33

Magone and colleagues applied such a model to evaluate the role of various cytokines, including IL-4, IFN-γ, and IL-12, in the early and late phases of ocular allergy using knockout (KO) mice and neutralizing antibodies. In this model,  multiple mice experimental groups, including:

• ragweed-sensitized wild type
• IL-4KO type
• IL-12KO type
• IFN-γKO type
• anti-IL-12/mAb-treated
• anti-IFN-γ m-Ab-treated mice were challenged with ragweed allergen ten days after immunization.

An additional group received recombinant murine IL-12. They found the anti IL-12 antibody-treated and IL-12KO type mice failed to show allergic cellular infiltration into the conjunctiva. IFN-γKO type mice, however, had a significantly stronger immediate-type hypersensitivity reactions and prolonged allergic cellular infiltration after ragweed exposure. Overall, their data provided evidence of IL-12 as an inducer of the late phase of ocular allergy. Additionally, the data suggest IFN-γ as a limiting factor of the late phase and a potential therapeutic cytokine in the prevention of chronic allergic disease. Further research is aimed at preventing initial sensitization to allergens.

Immunological aspects of allergy and anaphylaxis part 32

Experimental Models

Animal models of ocular allergies have been developed in the past years to establish new therapeutic approaches and assess immunological mechanisms. The current animal models are based on sensitization to and subsequent challenge with small numbers of allergens such as ovalbumin (Ova), ragweed pollen, or cat epithelium. The murine model of allergic conjunctivitis represents the presently preferred species for investigating the immunological basis of the disease.

Immunological aspects of allergy and anaphylaxis part 31

Treatment is aimed at reducing the local inflammation. Ocular mast cells stabilizer drops such asolopatadine are the mainstay of treatment. In addition, treatment of nasal symptoms with nasal anti-inflammatory sprays promotes patency of the nasolacrimal duct. This combination treatment allows the eye to drain excess allergens, therefore diminishing allergic responses in the eye.

Immunological aspects of allergy and anaphylaxis part 30

Atopic keratokonjungtivitis is observed in approximately 15 to 40% of patients with atopic dermatitis. Whereas allergic conjunctivitis is usually a self-limiting process,  atopic keratoconjunctivitis is chronic and can potentially cause loss of vision. Immunological and immunohistochemical studies reveal mast cells, IgE antibody, eosinophils, and other inflammatory cells in similar quantities to those found in allergic conjunctivitis. The finding of lymphocyte involvement explains the chronic nature of the disease as well as the threat to sight.  Additional findings include antibodies to ICAM-1 and HLA-DR throughout the ocular epithjelium, suggesting increased antigen presentation. Also, increased level of RANTES, an eosinophil homeostasis chemokine, are observed in immunochemical studies of the epithelium. Fibroblast numbers are increased in the connective tissue with an increased level of collagen compared with normal tissue. This infiltration is likely critical to the sight-threathening nature of the disease.

Immunological aspects of allergy and anaphylaxis part 29

The  major signs and symptoms include itching and a clear or white stringy discharge. A "cobblestone" appearance is typical. It is commonly associated with contact lens use. Foreign bodies and ocular sutures or prosthetics may be causal as well. Treatment typically involves  avoidance of the inciting process or use of ocular anti-inflammatory agents such as cromolyn sodium or topical corticosteroid.

Immunological aspects of allergy and anaphylaxis part 28

Giant papillary conjunctivitis is a chronic inflammatory process that leads to the production of giant mucosal ducts, or papillae, on the conjunctival lining of the upper eyelids. The immunopathologic mechanism is complex and is theorized to be a mechanical trauma culminating in a mast cell-mediated delayed-type hypersensitivity.