Allergen late-phase reactions

From 4 to 8 hours after the initial exposure to an allergen, a late-phase reaction may occur, which is thought to be due to cytokines released primarily by mast cells and thymus-derived helper lymphocytes. This inflammatory response likely is responsible for persistent, chronic symptoms including nasal congestion. 

Frew AJ, Corrigan CJ, Maestrelli P, Tsai JJ, et al. 1989. T lymphocytes in allergen-induced late-phase reaction and asthma. Int Arch Allergy Appl Immunol. 88 63-67. 

Type I hypersensitivity reactions usually occur within minutes to hours of exposure to an antigen in sensitized individuals. The immediate allergic response is initiated 5 to 30 minutes after allergen exposure and resolves in 30 to 60 minutes.This may be followed by the late-phase reaction, which is more severe and of greater duration. The late phase develops 4 to 6 hours after the initial response and may last up to 2 days. Neutrophils, eosinophils, macrophages, lymphocytes, basophils, and mast cells are involved in the late-phase inflammatory reaction, resulting in tissue damage. 

Anaphylactic reactions generally begin within 30 minutes but almost always within 2 hours of exposure to the inciting allergen. The risk of fatal anaphylaxis is greatest within the first few hours. After apparent recovery, anaphylaxis may recur 6 to 8 hours after antigen exposure. Because of the possibility of these late phase reactions, patients should be observed for at least 12 hours after an anaphylactic reaction. Fatal anaphylaxis most often results from asphyxia due to airway obstruction either at the larynx or within the lungs. Cardiovascular collapse may occur as a result of asphyxia in some cases, whereas in others cases cardiovascular collapse may be the dominant manifestation from the release of mediators within the heart muscles and coronary blood vessels. 

Both immediate and late-phase reactions are observed after allergen exposure. The immediate reaction occurs within minutes, resulting in the rapid release of preformed mediators and newly generated mediators from the arachidonic acid cascade as the mast cell membrane is disturbed (Table 93-1). These mediators of immediate hypersensitivity include histamine, leukotrienes (LTs) C4, LTD4, LTE4, prostaglandin D2, tryptase, and kinins. In addition, the mast... 

Ying, S., Meng, Q., Barata, L. T., and Kay, A. B. (2001). Macrophage inflammatory protein-lalpha and C-C chemokine receptor-1 in allergen-induced skin late-phase reactions Relationship to macrophages, neutrophils, basophils, eosinophils and T lymphocytes. Clin. Exp. Allergy 31, 1724. 

The allergen-induced late phase reaction has features of a cell-mediated hypersensitivity response but shows some significant differences best illustrated by the different cytokine profiles. 

Peebles RS, Permutt S, Togias A. Reversibility of the allergen-induced pulmonary late-phase reaction by an intravenous beta (2) agonist. J Appl Physiol 1998 84 1500-1505. 

Kato M, Liu MC, Stealey BA, Friedman B, Lichtenstein LM, Permutt S, Schleimer RP. Production of granulocyte/macrophage colony-stimulating factor in human airways during allergen-induced late-phase reactions in atopic subjects. Lymphokine Cytokine Res 1992 11 287-292. 

The late-phase inflammatory reaction occurs 6 to 9 hours after allergen provocation and involves recruitment and activation of eosinophils, T lymphocytes, basophils, neutrophils, and macrophages. 

Diaz P, Gonzalez MC, Galleguillos FR, Ancic P, Cromwell O, Shepherd D, et al Leukocytes and mediators in bronchoalveolar lavage during allergen-induced late-phase asthmatic reactions. Am RevRespirDis 1989 139 1383-1389. 

Relief of symptoms and signs—a reduction in the response of a target organ to the specific allergen. In pollen rhinoconjunctivitis, a reduced response to the instillation of pollen into the conjunctival sac would be relevant. A reduction in the skin reaction to the specific allergen, especially a reduction in the late phase skin response (IgE-mediated), may be demonstrated. In asthma, a reduction in the specific bronchial response to inhaled allergen with an associated reduction in non-specific reactivity (measured by histamine or methacholine provocation) would indicate a response to treatment. 

G, M., Frew, A.J., Varney, V.A. and Kay, A.B. (1991). Eosinophil activation and T-lymphocyte infiltration in allergen-induced late phase skin reactions and classical delayed-type hypersensitivity. J. Immunol. 147, 816-822. 

Rossi, G.A., Crimi, E., Lantero, S., Gianiorio, P., Oddeta, S., Crimi, P. and Brusasco, V. (1991). Late-phase asthmatic reaction to inhaled allergen is associated with early recruitment of eosinophils in the airways. Am. Rev. Respir. Dis. 144, 379-383. 

Not all cases of asthma can be attributed to reaction to an allergen. Other stimuli that cause asthma attacks include exercise, cold air, infections and atmospheric pollutants. In these cases symptoms may be produced through stimulation of irritant receptors and release of mediators from sensory neurones. Treatment of asthma of whatever cause is by use of bronchodilators to reverse the bronchospasm of the immediate phase and by anti-inflammatory dmgs to inhibit or prevent the development of the late phase. 

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