Advances in the knowledge of the cellular and molecular basis of immunity have led to an enhanced thorough understanding of the immunologic features that characterize an allergic response. A hallmark of an allergic response is a persistently elevated level of specific IgE antibodies to a variety of antigens, also referred to as allergens, to which the affected individual is regularly exposed by inhalation, ingestion, or contact with the skin.<sup>48 Marsh D.G. Genetics of asthma and other atopic diseases. In Post-Graduate Education Course New Orleans: American Academy of Allergy and Immunology (1996).  1-5

Haga clic aquí para ir a la sección de Referencias</sup> Allergic sensitization involves processing of the antigen by an antigen-presenting cell (APC) and presentation, in association with a class II major histocompatibility complex (MHC) protein, to a T-cell receptor. Whereas dendritic cells (and macrophages) predominantly act as APCs in primary immunization, B cells may also participate in secondary immune responses to allergens. Activation of T cells requires the first signal from this trimolecular interaction and an additional costimulatory signal involving the ligation of B-7 on an APC (CD80/86) with CD28 or CTLA4 on a T cell.<sup>27 Healy J.I., Goodnow C.C. Positive versus negative signaling by lymphocyte antigen receptors Annu Rev Immunol 1998 ;  16 : 645

Haga clic aquí para ir a la sección de Referencias</sup> When stimulated by antigens, helper T cells produce an array of specific cytokines, all of which have been designated as either T_H1 cytokines (interleukin [IL]-2, interferon [IFN]-γ, and tumor necrosis factor [TNF]-β) or T_H2 cytokines (IL-4, IL-5, IL-9, IL-10, and IL-13). The state of T-cell activation depends on several factors.<sup>27 Healy J.I., Goodnow C.C. Positive versus negative signaling by lymphocyte antigen receptors Annu Rev Immunol 1998 ;  16 : 645

Haga clic aquí para ir a la sección de Referencias, 85 Wills-Karp M. Immunologic basis of antigen-induced airway hyperresponsiveness Annu Rev Immunol 1999 ;  17 : 255  [cross-ref]

Haga clic aquí para ir a la sección de Referencias</sup> The first of these factors is the affinity of the interaction between the antigen and the T cell. The site of the antigen recognized by the T cell is termed the epitope. The affinity of epitope–T cell interaction is affected by the concentration of the antigen and the type of APC.<sup>80 Tsitoura D.C., Verhoef A., Gelder C.M. , y al. Altered T cell ligands derived from a major house dust mite allergen enhance IFN-⍺ production but not IL-4 production by human CD4 T cells J Immunol 1996 ;  157 : 2160

Haga clic aquí para ir a la sección de Referencias</sup> It also depends on the cytokine milieu of the T cell during antigen interaction. Thus, IFN-γ and IL-12 promote a T_H1-like response, whereas IL-4 promotes a T_H2-like response.<sup>12 Constant S.L., Bottomly K. Induction of T_H1 and T_H2 CD4+ T cell responses: The alternative approaches Annu Rev Immunol 1997 ;  15 : 297  [cross-ref]

Haga clic aquí para ir a la sección de Referencias</sup> Additionally, host immune response genes may bias the overall immune responsiveness of an individual to favor a T_H1- or T_H2-like response. A T_H2-like cytokine profile is associated with the induction of IgE antibody (Ab) production in vitro and in vivo.<sup>73 Romagnani S. Lymphokine production by human T cells in disease states Annu Rev Immunol 1994 ;  12 : 227  [cross-ref]

Haga clic aquí para ir a la sección de Referencias</sup> Specifically, IL-4 favors the development of T_H2-like cells from uncommitted T cells, and both IL-4 and IL-13 play a role in IgE antibody production.

Manifestation of an allergic reaction depends on the specific IgE levels and the amount of exposure at the time of the reaction. Although an allergic condition is a risk factor for asthma, about 20% to 30% of asthmatics do not show positive skin tests to allergens. In general terms, asthma is defined as an inflammatory disease where not only lymphocytes, but also other cells, such as mast cells, basophils, eosinophils, and epithelial cells, play a role. Studies to date suggest that T_H2-like cytokines, such as IL-4 and IL-5, also play an important role in nonatopic asthma.<sup>3 Bochner B.S., Undem B.J., Lichtenstein L.M. Immunological aspects of allergic asthma Annu Rev Immunol 1994 ;  12 : 295  [cross-ref]

Haga clic aquí para ir a la sección de Referencias, 85 Wills-Karp M. Immunologic basis of antigen-induced airway hyperresponsiveness Annu Rev Immunol 1999 ;  17 : 255  [cross-ref]

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Developing immunotherapeutic approaches against allergic diseases, including asthma, may be pragmatically divided into two categories based on how soon they may make an inroad to the clinic, as shown in Figure 1. The first category includes therapies that are already in phase II/phase III clinical trials and are expected to be available in clinics within the next 1 to 3 years; such therapies include antihuman IgE antibodies and the soluble IL-4 receptor. The second category includes experimental approaches that are mainly at the stage of preclinical research in model systems and may proceed to clinical trials and the clinic within the next 5 to 10 years; these therapies include various allergen-specific and allergen-nonspecific approaches.