**3. Results/findings**

Critical analysis of scientific concepts in pulmonary immune inflammation of asthma and allergic rhinitis and an analysis of similarities, differences, and interactions between these two diseases are done.

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 therapies for asthma.

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 airway epithelium [10, 11].

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 degranulation of mast cells.

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 disease (**Table 1**).

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

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.


#### **Table 1.**

*Classification of the immune system, immune cells, and the inflammatory response in asthma summary of functions.*

Phagocytic cells are a part of the innate immune system and consist of polymorphonuclear cells, monocytes-macrophages, and eosinophils. Neutrophils and monocytes are normally found circulating in the bloodstream and are recruited to sites of infection by the process of extravasation. Receptors on the phagocyte interact with ligands on vascular endothelium, and the cells attach, arrest, and move from the circulation to the diseased tissue/lungs.

Monocytes, similar to neutrophils, can also migrate into the tissues and on doing so differentiate into macrophages. Macrophages have a number of key functions, including phagocytosis of infecting microbes, antigen presentation, and general removal of dying or damaged host cells [12].

#### *3.1.1 Dendritic cells*

These are bone marrow-derived cells, found in most tissues, including lymphoid tissues. Discovered by Ralph Steinman in the mid-1970s, dendritic cells are critical for the initiation of the immune response. They are so named, because of being covered with long membranous extensions that resemble the dendrites (extensions) of the nerve cells.

Dendritic cells capture antigens, e.g., pollen/animal dander, and process these antigens and then present them to naive T cells, initiating the adaptive immune response. The first stage of an immune response to any antigen is the processing and presentation of that antigen by antigen-presenting cells (APCs), e.g., dendritic cells.

#### *3.1.2 Pattern recognition receptors (PRRs)*

These are receptors of the innate immune system that recognize common molecular patterns on pathogen surfaces called pathogen-associated molecular patterns (PAMPS), structures that are conserved in broad classes of pathogens for their functional importance. Many of these receptors reside at the plasma

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

pathogen surfaces.

immune response.

proteins act as virus receptors

vates innate immune responses.

gens arrive in the cytoplasm:

bacteria.

*3.1.3 Mast cells*

epithelial cells.

membrane. They are proteins expressed, mainly, by cells of the innate immune system, such as dendritic cells, macrophages, monocytes, neutrophils, and

i.One group of receptors, **C-type lectins**, recognizes certain sugar units that are typically located at the terminal position of carbohydrate chains on

ii.Another group and one of the best-characterized signaling PRR families is the evolutionary conserved **toll-like receptor system** in mammals, named after a homologous receptor system used by the *Drosophila* fruit fly for protection from infection. In humans, there are 10 expressed TLR genes in mice [13], their products forming homo- or heterodimers with other family members, thus increasing the repertoire for recognition. TLR4, for example, has been shown to be the receptor recognizing lipopolysaccharide (LPS) found on the surface of Gram-negative bacteria such as *Escherichia coli* but not present on mammalian cells. The effect of pathogen components binding to TLRs on innate immune cells is TLR activation, which initiates signaling into the immune cell and the increased expression of a large number of target genes. The genes involved depend on the pattern of TLRs engaged, but common outcomes include the increased production of inflammatory mediators such as cytokines and chemokines, enhanced phagocytosis (internalization and killing of the pathogen), upregulation of costimulatory molecules on the cell surface, cell migration, and, in the case of macrophages, increased processing and presentation of pathogen antigens to activate an adaptive

There are also three other families of receptors that sense PAMPS when patho-

ii.RIG-like helicases (RLHs): the cytoplasmic RNA-helicase, RIG-I, and related

• NLRs is an acronym that stands for NOD-like receptors. These are a large family of cytosolic proteins activated by intracellular PAMPS. NOD1 and NOD2 recognize important PAMPS, e.g., muramyl dipeptides produced during the synthesis or degradation of either intracellular or extracellular

• cGMP-AMP (cGAMP) synthase (cGAS) is a cytosolic DNA sensor that acti-

A large granule-rich cell found in the connective tissue of the body, most abundantly in the submucosal tissues and the dermis. The granules store bioactive

i.NOD-like receptors (NLRs): e.g., NOD1 and NOD2

iii.Cyclic GMP-AMP synthase (cGAS, cGAMP synthase): NB

Functions of NOD1 and NOD2 and cyclic GMP-AMP synthase:

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

*Rhinosinusitis*

A. Innate immune system

B. Adaptive immune response

C. Bronchial epithelial cells

**Table 1.**

Phagocytic cells are a part of the innate immune system and consist of polymorphonuclear cells, monocytes-macrophages, and eosinophils. Neutrophils and monocytes are normally found circulating in the bloodstream and are recruited to sites of infection by the process of extravasation. Receptors on the phagocyte interact with ligands on vascular endothelium, and the cells attach, arrest, and

*Classification of the immune system, immune cells, and the inflammatory response in asthma summary of functions.*

Monocytes, similar to neutrophils, can also migrate into the tissues and on doing so differentiate into macrophages. Macrophages have a number of key functions, including phagocytosis of infecting microbes, antigen presentation, and general

These are bone marrow-derived cells, found in most tissues, including lymphoid tissues. Discovered by Ralph Steinman in the mid-1970s, dendritic cells are critical for the initiation of the immune response. They are so named, because of being covered with long membranous extensions that resemble the dendrites (extensions)

Dendritic cells capture antigens, e.g., pollen/animal dander, and process these antigens and then present them to naive T cells, initiating the adaptive immune response. The first stage of an immune response to any antigen is the processing and presentation of that antigen by antigen-presenting cells (APCs), e.g., dendritic cells.

These are receptors of the innate immune system that recognize common molecular patterns on pathogen surfaces called pathogen-associated molecular patterns (PAMPS), structures that are conserved in broad classes of pathogens for their functional importance. Many of these receptors reside at the plasma

move from the circulation to the diseased tissue/lungs.

**Pulmonary immune cell types/**

Pattern recognition receptors

Phagocytic cells (polymorphonuclear cells, monocyte-macrophages, and

**Summary of functions**

Airway dendritic cells (DC) are critical mediators of immune responses in the lung by virtue of their ability to sample, process, and

The interleukins IL-25 and IL-33 and thymic stromal lymphopoietin are produced by injured epithelium and play critical roles in driving expression of Th2 cytokines

present inhaled antigens to T cells

**receptors**

eosinophils) Dendritic cells Mast cells Eosinophils Basophils

TREG cell Natural killer cells NKT cells IL2 cells

T and B cells

• Clara cells • Ciliated cells • Goblet cells

removal of dying or damaged host cells [12].

*3.1.2 Pattern recognition receptors (PRRs)*

*3.1.1 Dendritic cells*

of the nerve cells.

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membrane. They are proteins expressed, mainly, by cells of the innate immune system, such as dendritic cells, macrophages, monocytes, neutrophils, and epithelial cells.


There are also three other families of receptors that sense PAMPS when pathogens arrive in the cytoplasm:


Functions of NOD1 and NOD2 and cyclic GMP-AMP synthase:


#### *3.1.3 Mast cells*

A large granule-rich cell found in the connective tissue of the body, most abundantly in the submucosal tissues and the dermis. The granules store bioactive molecules including the vasoactive amine, which are released on mast cell-activated and are involved in the pathogenesis of bronchoconstriction in asthmatic airways [13, 14].
