Atopy or Allergic disease is a complex familial disorder with multiple manifestations, including allergic asthma, rhinitis, conjunctivitis, and dermatitis. Allergens are derived from different sources such as cockroaches, ragweed pollens, and house dust mites. The primary immune cell lineages involved in the initiation and progression of allergic inflammation include DCs (Dendritic Cells), mast cells, basophils, eosinophils, and Th2 (Type-2 Helper T) cells. The responses of these principal players in allergic reactions are influenced by the local environments in which they reside. When susceptible or atopic individuals are initially exposed or sensitized to allergens, Antigen-presenting cells capture, process, and present allergen as an allergen-derived peptide fragment in the contest of specific MHC II (HLA II) molecules this induces allergen-specific acquired immune responses, which are characterized by CD4+ T cells that produce a Th2 profile of cytokines for example, IL-4(Interleukin-4), IL-5, IL-9 and IL-13, IL-10 and the presence of allergen-specific IgE. Subsequent challenge with allergen causes the rapid activation of mast cells through allergen and IgE crosslinking, and the release of mediators such as histamine and leukotrienes causes increases in vascular permeability, smooth-muscle contraction and mucus secretion. Late-phase allergic responses are characterized by the additional recruitment and activation of eosinophils and Th2 cells at the site of allergen challenge (Ref.1, 2 & 3).
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Viola JP, Kiani A, Bozza PT, Rao A. Blood. 1998 Apr 1;91(7):2223-30. 2.The influence of TSLP on the allergic response. Comeau MR, Ziegler SF. Mucosal Immunol. 2010 Mar;3(2):138-47. doi: 10.1038/mi.2009.134. 3.Identification of antigenic epitopes on human allergens: studies with HLA transgenic mice. Chapoval SP, David CS. Environ Health Perspect. 2003 Feb;111(2):245-50. 4.Role of mast cells in allergic and non-allergic immune responses: comparison of human and murine data. Bischoff SC. Nat Rev Immunol. 2007 Feb;7(2):93-104. 5.Potential role of interleukin-10-secreting regulatory T cells in allergy and asthma. Hawrylowicz CM, O'Garra A. Nat Rev Immunol. 2005 Apr;5(4):271-83. 6.Eotaxin: from an eosinophilic chemokine to a major regulator of allergic reactions. Gutierrez-Ramos JC, Lloyd C, Gonzalo JA. Immunol Today. 1999 Nov;20(11):500-4. 7.Improvement of cellulase activity using error-prone rolling circle amplification and site-directed mutagenesis. Vu VH, Kim K. J Microbiol Biotechnol. 2012 May;22(5):607-13. 8.Th2 cell-selective enhancement of human IL13 transcription by IL13-1112C>T, a polymorphism associated with allergic inflammation. Cameron L, Webster RB, Strempel JM, Kiesler P, Kabesch M, Ramachandran H, Yu L, Stern DA, Graves PE, Lohman IC, Wright AL, Halonen M, Klimecki WT, Vercelli D. J Immunol. 2006 Dec 15;177(12):8633-42. 9.Eosinophil cationic protein (ECP) is processed during secretion. Woschnagg C, Rubin J, Venge P. J Immunol. 2009 Sep 15;183(6):3949-54. doi: 10.4049/jimmunol.0900509. 10.Eosinophil-derived neurotoxin acts as an alarmin to activate the TLR2-MyD88 signal pathway in dendritic cells and enhances Th2 immune responses. Yang D, Chen Q, Su SB, Zhang P, Kurosaka K, Caspi RR, Michalek SM, Rosenberg HF, Zhang N, Oppenheim JJ. J Exp Med. 2008 Jan 21;205(1):79-90. doi: 10.1084/jem.20062027. 11.Inhibitory effects of ketotifen on eotaxin-dependent activation of eosinophils: consequences for allergic eye diseases. Woerly G, Loiseau S, Loyens M, Schoch C, Capron M. Allergy. 2003 May;58(5):397-406. 12.Signal transduction around thymic stromal lymphopoietin (TSLP) in atopic asthma. Sebastian K, Borowski A, Kuepper M, Friedrich K. Cell Commun Signal. 2008 Aug 25;6:5. doi: 10.1186/1478-811X-6-5. |