#immunoregulation

New Post has been published on http://the-asthma.com/allergy-and-asthma-treated-by-ventolin-inhaler.html

Allergy and Asthma Treated by Ventolin Inhaler

Asthma, particularly in the young, is a disease associated with an underlying atopic allergic hypersensitivity to one or more allergens. Atopic allergic sensitization is defined by production of IgE against environmental antigens such as proteins from house dust mites (HDMs), grass pollens, animal dander, insects, and foods. Allergic sensitization can lead to a variety of clinical manifestations including asthma, rhinitis, and atopic dermatitis. Allergic sensitization to common allergens can be detected in > 25% of the population of some industrialized nations,3 and the prevalence of allergic disease has increased markedly within the last 50 years. While atopy and the development of allergic diseases are associated with multiple susceptibility genes, it is clear that there has been no substantial change in the human genome in the last 50 years. It follows, therefore, that environmental factors contribute significantly to the recent increases in disease prevalence. Moreover, similar dramatic trends have been observed in autoimmune diseases such as type I diabetes and multiple sclerosis.4 Epidemiologic observations linking prevalence of allergic sensitization with birth order together with numerous subsequent studies investigating the influence of environmental stimuli on the allergic diathesis have lead to the development of the “hygiene hypothesis.” The central canon of the hypothesis is that reductions in exposure to infectious disease and microbial products (through the introduction of vaccines, antibiotics, and improved sanitation) in recent decades has resulted in deficient immune regulation resulting in hypersensitivity in both the T-helper type 1 (Th1) and T-helper type 2 (Th2) compartments.

In addition to the humoral IgE component, allergic immune responses are characterized by Th2 T cells specific for the allergen, and the production of Th2 cytokines (interleukin [IL]-4, IL-5, IL-9, IL-13, and others) and Th2-associated chemokines (thymus and activation-regulated chemokine [TARC], monocyte-derived chemokine [MDC]). IL-4 and IL-13 act as Ige heavy chain isotype switch factors leading to the production of IgE. IL-4, IL-5, and IL-9 enhance the survival of eosinophils and their progenitors and prime these cells for activation and chemotaxis. IL-9 is a growth factor for mast cells, and IL-13 has been associated with goblet-cell hyperplasia, mucus hypersecretion, and airway hyperresponsiveness (AHR). TARC and MDC recruit Th2 T cells to sites of allergic inflammation. Whether existing Th2 T cells are required to initiate IgE responses, or whether the presence of allergen-specific IgE is required to generate allergen-specific Th2 responses remain unresolved. The key element in asthma treatment is Ventolin for Asthma.

The acute or early phase of allergic inflammation is initiated when the allergen comes into contact with IgE-primed mast cells/basophils. Cross-linking of allergen-specific IgE on the surface of mast cells and basophils leads to the release of mediators including substantial quantities of Th2 cytokines. Mast cell/ basophil activation therefore may be sufficient to create the Th2 cytokine milieu that drives Th2 T-cell differentiation and expansion. Expression of IgE receptors on antigen presenting cells (eg, dendritic cells [DCs] and monocytes) allows these cells to capture allergen in a specific fashion through surface-bound IgE.6 The same is true of allergen-specific B cells that express specific membrane Ig. Facilitated antigen presentation of this kind promotes Th2 T-cell differentiation and activation and contributes to dysregulated immune responses to allergen. Thus, allergen-specific IgE amplifies allergen-specific Th2 responses and vice versa. Activation of mast cells/basophils results in the release of mediators such as histamine and leukotrienes that cause bronchoconstriction and airway narrowing through mechanisms that include elements of smooth-muscle constriction and edema.

The late phase of the allergic reaction is characterized by recruitment of activated CD4+ Th2 T cells and eosinophils to sites of allergen exposure. Release of Th2 cytokines (particularly IL-5) from T cells (and mast cells/basophils in the early phase response) leads to the mobilization of bone marrow eosinophils and their progenitors. Local eosinophil recruitment occurs under the influence of chemo-kines such as eotaxin released from structural cells at the site of allergen exposure. Eosinophils are believed to be important effector cells in the late asthmatic reaction (the late-phase allergic response in the airways of asthmatic individuals), causing epithelial cell damage through release of toxic granule proteins, bronchoconstriction through leukotri-ene production, and contributing to AHR.7 However, clinical studies’9 with neutralizing monoclonal antibodies to IL-5 showed no effect on airway function despite marked reduction in numbers of circulating eosinophils. Activation of allergen-specific Th2 T cells with synthetic peptides representing the immunodominant T-cell epitopes of an allergen can lead directly to symptoms of asthma and increased AHR in the absence of the mast cell/basophil component.”11 This relatively recent observation suggests that airway narrowing can occur through both early and late-phase allergic mechanisms, both of which are linked directly and indirectly to allergen-specific T cells and allergen-specific IgE.