The Immunology of Asthma and Allergic Rhinitis

*Andrew Kiboneka and Dan Kibuule*

### **Abstract**

The immune system is a complex collection of cells, tissues, and chemical mediators positioned throughout the body, whose primary purpose is to protect us against infection. However, its function is not only fundamental in protection from infectious disease but also provides aberrant response in allergens such as with asthma and allergic rhinitis. Allergic diseases like asthma and allergic rhinitis are characterized by a distinct type of inflammatory response, driven by immunoglobulin E (IgE)-dependent mechanisms. In asthma and allergic rhinitis, the inflammatory response is mediated by interaction of several immune cells (monocytes, lymphocytes, and polymorphonuclear cells) and cellular chemical mediators. In particular, atopic allergic response leads to destruction of multiple target cells such as epithelial, parenchymal and vascular and connective tissue of the airways. In addition, in inflammatory response in asthma and allergic rhinitis, sensory nerves are sensitized, leading to clinical manifestations. Sneezing and coughing are hypersensitivity responses of sensory nerves in allergic rhinitis and asthma, respectively. Similarly, nasal congestion and discharge in allergic rhinitis are due to vasodilatation that leads to plasma exudates as well as mucous secretion. The allergic inflammatory response is regulated by several transcription factors, particularly nuclear factor-κb (NF-κB), GATA-3 protein 3, and GATA binding protein.

**Keywords:** immunology, asthma and allergic rhinitis,, TH2 high, TH2 low, IL2 cells, Clara cell secretory protein (CC16), thymic stromal lymphopoietin (TSLP), interleukin (IL)-33, phenotypes, endotypes, united airway hypothesis, biological agents

### **1. Introduction**

Allergic responses are mediated by IgE, a type of antibody associated with mast cells and basophils [1, 2]. Allergic rhinitis (i.e., inflammation of epithelia of nostril) is a reaction to allergens in the environment such as dust, pollen grain, and animal dander, among others. Patients with allergic rhinitis often present with congestion and inflammation (i.e., pain, reddening, and swelling) of the mucous membranes of the upper respiratory tract (nose, throat, eyes, and ears). In contrast, asthma is a complex heterogeneous syndrome characterized by increased inflammatory cells, airway hyper-reactivity (AHR), and structural changes in the lung [3]. The histological features of asthma include edema, cellular infiltration (typically with a prominent T lymphocyte and an eosinophil component), and sub-basement membrane collagen deposition.

Asthma is defined according to the Global Initiative for Asthma (GINA) 2018 as a heterogeneous disease, usually characterized by chronic airway inflammation. Asthma is induced by an inflammatory response against usually manageable environmental inorganic and organic compounds in the respiratory tract. Indeed, asthma attacks can be triggered by exercise, viral illness, and allergens such as pollen. Other triggers include medications, extremes of weather, stress, smoke, and certain foods. Key indicators include a history of respiratory symptoms such as wheeze, shortness of breath, chest tightness, and cough that vary over time and in intensity, together with variable expiratory airflow limitation. It has variations in severity, natural history, and response to therapy [4].

Patients diagnosed with atopy have an increased likelihood to allergic responses mediated via IgE, mast cells, and CD4+ lymphocytes. In atopy, the allergic inflammatory responses are mainly due to cytokines (interleukins (IL-3, IL-4, and IL-5)) released from CD4+ lymphocytes. The interleukins increase the IgE production to neutralize the allergens. However, the binding of IgE-allergen complex formed further induces de novo synthesis and release of vasoactive substances that exacerbate the inflammatory reaction. This allergic inflammatory response occurs in two stages (early and late response) in both asthma and allergic rhinitis.

The allergic immune response recognizes allergens via germ line or random encoding, which can be innate and adaptive. The innate allergic immune responses are the first line of defense against allergens that use germ-line encoding and phagocytic cells. In contrast, the adaptive allergic response is mainly designed against infection and allergenic proteins from weed and pollen.

#### **1.1 Pathogenesis of allergic rhinitis and asthma**

According to the World Health Organization (WHO), the burden of asthma is estimated to have 300 million cases worldwide, making it one of the commonest noncommunicable diseases. Asthma is a serious global health problem affecting all age groups, with increasing prevalence in developing countries, treatment costs, and a burden for patients and the community. The WHO ranks asthma the highest among chronic illnesses afflicting the pediatric population worldwide. Of concern is that the majority of case fatalities attributed to asthma occur among populations in underdeveloped countries characterized with weak health systems for control and management of the disease [4–7].

Whereas allergic rhinitis results from activation of mucosal mast cells, asthma is triggered by allergen activation of submucosal mast cells in the lower airways. The nature and development airway inflammation may be driven by numerous factors, including pathogenic infections, pollution, or even relatively innocuous inhaled particles, such as allergens. International guidelines are available for the management of severe asthma by the European Respiratory Society and the American Thoracic Society [6].

Chronic allergen exposure leads to the continuous presence of increased number of lymphocytes, eosinophils, neutrophils, basophils, and other leukocytes causing airway hyper-reactivity and remodeling—a thickening of the airway walls due to hyperplasia and hypertrophy of the smooth muscle layer, with the eventual development of fibrosis.

It has become apparent that there are many phenotypic and endotype types of asthma. In patients with allergic asthma endotypes, allergen can cause activation of mast cells in an antigen-specific manner. Also allergens can stimulate the airway epithelium, through toll-like receptors (TLRs) and other damage receptors, to release IL-25, IL33, and thymic stromal lymphopoietin (TSLP). These cytokines can lead to the activation of submucosal type two innate lymphoid cells (ILC2), inducing these to release IL-4, IL-5, IL-9, and IL-13.

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*The Immunology of Asthma and Allergic Rhinitis DOI: http://dx.doi.org/10.5772/intechopen.86964*

Education (Cochrane Collaboration) [7–9].

tions between these two diseases are done.

A comprehensive review of all aspects of immunology, components of the immune system, immune responses to asthma and allergic rhinitis in children and adults, and airway epithelial cell mucosal immunology was done in a systematic and explicit search of PubMed and HINARI—identifying, selecting, and critically appraising relevant research and textbooks of Immunology from Europe and the United States of America used in undergraduate and postgraduate Medical

Critical analysis of scientific concepts in pulmonary immune inflammation of asthma and allergic rhinitis and an analysis of similarities, differences, and interac-

Knowledge of our immune system functions is critical in understanding allergic airway disease development as well as for selection of appropriate diagnostic and therapeutic options for patients with asthma and allergic rhinitis. A robust inflammatory response is essential to control asthma and allergic rhinitis, and both active and innate mechanisms of immunity are important in this regard. The failure of resolution or persistent pro-inflammatory immune responses results in chronic inflammatory airway diseases like asthma and allergic rhinitis. It is also becoming increasingly important to phenotype airway inflammation in individual patients to allow targeted treatment as we move toward personalized

The majority of patients of asthma suffer from an allergic variant of the disease that is triggered by an IgE-driven immune response directed against inhaled antigens and leads to various symptoms, such as wheezing, coughing, and breathing difficulties. The immunopathogenesis of allergic asthma involves a complex interplay between the immune system and parenchymal cells of the lung, including the

Inhaled allergens are phagocytosed by macrophages and dendritic cells (DCs) presented on major histocompatibility complex (MHC) class II molecules and initiate the differentiation of Th2 cells and a humoral immune response. Following class switching, Ag-specific B cells secrete immunoglobulin E which causes degranula-

Cytokines, such as IL-4, IL-5, and IL-13, are produced by TH2 cells, mast cells, basophils, and type 2 innate lymphoid cells, as well as airway epithelial cells, and they trigger pathological events, including airway wall remodeling, bronchial hyper responsiveness, and goblet cell metaplasia. Once the immune response has been initiated, eosinophils become the major effector cells that are responsible for airway dysfunction. In addition to the importance of immune cells in allergic asthma, there is evidence for a prominent role of airway epithelial cells in this

**3.1 The innate inflammatory immune response and asthma/cells of the immune** 

Innate immunity is the body's immediate response to an infection. It is a nonspecific response, meaning that the same response is mounted to a large number of different pathogens. When activated, the innate response is often seen as an inflammatory response. Inflammation is the body's response to injury or tissue damage.

**2. Methodology**

**3. Results/findings**

therapies for asthma.

airway epithelium [10, 11].

tion of mast cells.

disease (**Table 1**).

**system**
