Asthma represents a chronic inflammatory process of the airways followed by structural modification at the tissue level and referred to as remodeling of the airways (Anastasiou et al., 2003).
1.7.1. Characteristic of Airway Remodeling in Asthma
Structural changes in the airway of asthmatics: The airway wall of asthmatic patient is characterized by increased thickness due to increase in muscle mass, mucus glands and vessel area resulting in increased resistant to airflow, leading bronchial contraction and bronchial hyper-responsiveness. The presence of increased mucus secretion and inflammatory exudates not only blocks the airway passages but causes increased surface tension favoring airway closure.
Hypertrophy and hyperplasia of airway smooth muscle: Increase in smooth muscle cell mass may be due to the proliferation of smooth muscle induced by inflammatory mediators, cytokines and growth factors. The repeated episodes of bronchospasm or reduced inhibitory control results in myogenic activity and hypertrophy. Smooth muscle mitogenesis and hyperplasia occur due to the accumulation of increased amount of plasma in the surrounding area of airway smooth.
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Increase in mucus glands: Hypertrophy of submucosal gland mass is thought to be the reason for excessive mucus production in fatal asthma (Jean et al., 2000).
1.8. The immune response
The basic feature of the asthma associated with allergic sensitization is the capability of the airway to recognize common environmental allergens and to generate a Th2 cytokine response against them. The IgE bound to high affinity receptors on dendritic cells enhance the uptake of the allergens and facilitate allergen internalization (Kitamura et al). This is fundamental to the ability of these cells to serve as antigen presenting cells to lymphocytes (Riese and Chapman 2000).
Once the dendritic cell has engaged allergen or when it becomes ready to antigen presentation, it receives signal to migrate to local lymphoid collections where antigen presentation takes place. The specific chemokines receptors on them, including CCR7 and its ligands are involved in this chemotactic migration to enable contact with naive T cells- (newly formed T cells) (Humrich et al. 2006). Presentation of a selected antigen peptide to the T-cell receptor causes sensitization and the subsequent immune response to the specific allergen which has been presented (Smit & lukacs. 2006). The nature of this immune response mainly depends on whether engagement of selective co stimulatory molecules occurs in parallel. The capability of dendritic cells to generate interleukin (IL) -12 determines the balance between Th1 and Th2 responses, in favor of a Th1 response IL -12 polarizing T-cell differentiation (Kuipers et al . 2004). However, IL-12 have a role to counter act Th2 sensitization, it is also able to contribute to maximal expression of allergic airway disease post sensitization (Meyts et al. 2006). Once sensitized, T cells migrates back to the airways to the site of antigen presentation under the inÃ¯Â¬â€šuence of the chemokines CCL11, CCL2 4, CCL2 6, CCL7, CCL13, CCL17 and CCL2 2 which interact with their reciprocal receptors including CCR3, CCR 4, CCR5, CCR 6, CCR7 and CCR 8) (Garcia et al. 2005), these cells also produces a range of cytokines, the majority of which are expressed on the long arm of chromosome 5, namely IL-3, I L- 4, IL-5, IL-6, IL-9, IL-13 and granulocyteââ‚¬" macrophage colony stimulating factor (GM-CSF ) ( Ryu et al. 2006). The macrophages, monocytes, dendritic cells, and smooth muscle and epithelial cells are producing IL-1 b in large amounts (Dragon et al. 2006) and IL -2 produced by T cells further induces antigen induced T-cell proliferation and maturation (Ander son 2002).
Th2-type T cells may be important in the pathogenesis of mild to moderate asthma. Through cytokine production, they have the capacity to recruit secondary effector cells such as macrophages, basophils and eosinophils into the inÃ¯Â¬â€šammatory zone where these cells become primed and subsequently activated for mediator secretion (Akbari et al. 2006; Umets u & Dekruyf f 2006). As the disease becomes more severe and chronic Th1-typ e T cells are recruited that have the capacity to secrete tumor necrosis factor (TNF)-ÎÂ± and interferon (IFN)- g (Truyen et al . 2006). The T lymphocyte has been given primacy with regard to the orchestration of the inflammatory response in asthma.
Figure 4. Development of Chronic asthma
1.8.1. Airway inflammation is fundamental to asthma pathogenesis.
Airway inflammation in asthma is a multi cellular process in which eosinophils, neutrophils, CD4+T lymphocytes and mast cells are involved mainly. The inflammatory process mainly occur commonly in the conducting airways but as the disease becomes more severe and chronic the inflammatory infiltrate spreads both proximately and distally to include the small airways and in some cases adjacent alveoli (Kraft et al 2006). The Th2 type of inflammation is common to chronic allergic inflammatory responses at multiple tissue sites. It is most commonly seen at these sites in patients with asthma who frequently express co-morbidities such as chronic rhinitis, sinusitis, atopic dermatitis, and food allergy.
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Figure 5. Immune response of cells in allergic asthma