**5.1 Immediate type IgE-mediated hypersensitivity**

IgE mediated hypersensitivity is acute and the inflammation occurs immediately (within 30 mins) after exposure to an antigen (allergen). Allergen specific IgE antibodies binds to the FcεRI receptors present on basophils and mast cells. Exposure to allergen, specifically recognize the FCεRI bound IgE and cross link the adjacent IgEs and activate the signal cascade to trigger mast cell or basophils degranulation. The energy dependent degranulation process releases the non-cytotoxic, preformed

*Immunological Basis for the Development of Allergic Diseases-Prevalence, Diagnosis… DOI: http://dx.doi.org/10.5772/intechopen.95804*

inflammatory mediators that are responsible for induction of allergic symptoms within few minutes [18, 19]. Cellular degranulation releases two types of allergic mediators. Histamine, serotonin and tryptase are preformed mediators that are released by granular exocytosis. Other mediators like prostaglandins, leukotrienes were immediately synthesized de novo and released which act as pro-inflammatory signaling molecules. The two-phase mediators cause effect on glandular secretion, vascular permeability and smooth muscle contraction. These increase the immune cellular infiltration to the site of the inflammation within few minutes to hours and induce allergic reactions and referred as immediate hypersensitivity [20]. The allergic mediators, manifest and cause inflammation in many tissue sand organs (gastrointestinal system, respiratory system or generalized) either locally or systematically based on site of response (**Figure 1**). The symptoms range from mild atopic hay fever, rhinatisis, eczema to a chronic asthma and severe life threatening anaphylaxis.

#### **5.2 Allergic sensitization and reaction**

In an allergen sensitized subject with atopy, exposure of skin, nose, or airways to a single dose of allergen produces cutaneous wheal-and-flare reaction, sneezing and runny nose, or wheezing within minutes (**Table 3**), respectively [21, 22]. Depending upon duration and amount of allergen exposure the severity of allergic reaction may occur. Most IgE mediated hypersensitive reactions were immediate and express the clinical symptoms within an hour time. This may reach peak with late phase reactions in about 6 to 9 hours and after subsidizes slowly and resolves. In skin (**Figure 2**), the immediate reaction was characterized by itching and swelling and the late phase reaction by edematous erythoma which is read and forms blisters. In lungs it is noticed with nasal blockage, bronchial hyper responsiveness and further wheezing [22].

The type I hypersensitivity reaction has two stages, the earlier sensitization phase and the later effector phase. During the sensitization, the body encounter the antigen (allergen) for the first time and was recognized by the antigen presenting cells (APCs) as foreign antigen. The cells phagocytosed the antigen and present on the surface through MHC-II molecules. The naïve T helper lymphocyte recognize the presented antigen on MHC II and polarize the response towards Th2 by producing cytokines like interleukin −4 (IL-4) and interleukin −10 (IL-10). These interleukins interact with other type of lymphocytes known as B cells through specific receptors and instruct them through signal transaction that modulate gene transcription resulting in production of Immunoglobulin E (IgE) antibodies [23]. B cell turns into plasma cells and secrete large amount of IgE which circulates in the blood and on reaching basophils and mast cells, they recognize the specific receptors and binds the cell surface. The FcεR1 receptor has high affinity to IgE Fc portion and this referred as allergen sensitization. There was no observed inflammation or appearance of allergic symptoms during the sensitization phase.

#### **5.3 Acute response**

After the sensitization to allergen, the body had synthesized the IgE antibodies which occupied the surface of granulocytes; mast cell and basophils. The second exposure to the allergen, directly encounters the specific IgE antibodies present on the surface of allergic mast cells and basophils. The cross linking of two adjacent IgE molecules through multivalent allergen initiate the degranulation of these cells by activation of signaling cascade which results in exocytosis of preformed granular contents into the cellular space. The released histamine and other inflammatory chemical mediators (cytokines, interleukins, prostaglandins and leukotrienes)

#### **Figure 1.**

*(I) Enhanced IgE dependent effector function and potential immunoregulatory function in mast cells or basophils after IgE-dependent upregulation of Fc*ε*RI surface expression (\*\*\*Wedemeyer et al., 2000). (II). Mechanism that triggers the degranulation of mast cell or basophils. Crosslinkage can be mediated by: (A) the allergen that initiated the IgE response.*

induce systemic effects such as mucous secretion, smooth muscle contraction and vasodilatations [24, 25]. This results in the exacerbations of allergic symptoms like rhinorrhea, itchiness, dyspnea and anaphylaxis. Depending on the immune sensitivity of individual and mode and duration of exposure to allergen, the symptoms can be localized (organ or tissue specific); as asthma is localized to respiratory system and eczema to dermis or system-wide (classical anaphylaxis) where the whole body response with systemic effects.

*Immunological Basis for the Development of Allergic Diseases-Prevalence, Diagnosis… DOI: http://dx.doi.org/10.5772/intechopen.95804*


*prostaglandin D2.*

#### **Table 3.**

*Properties of human mast cells and basophils.*

#### **Figure 2.**

*The progression of allergic inflammation (e.g. in skin on testing), shows the schematic representation and components involved in the development of early-phase and late-phase reactions.*

#### **5.4 Late-phase response**

Acute chemical mediators induce immediate allergic response. Once these acute response subsidies, often other leukocytes such as neutrophils, eosinophils and macrophages migrate to the site of inflammation to phagocytose and clear the damaged or inflamed tissues and cells. This results in allergic late phase response that usually lapse for 2 to 24 hours depending upon the site of inflammation and kind of allergic reaction [26]. Some time, the cytokines released from the degranulated mast cells play a role in inducing long term late phase allergic reactions that extend the symptoms for long duration. In case of allergic asthma, the late phase response

#### *Cell Interaction - Molecular and Immunological Basis for Disease Management*

persist longer that results in bronchoconstriction, impairing the lung function and cause wheezing.

Acute and late phase allergic response and their specific symptomatic disease [25, 26].

a.Immediate (early-phase reaction)


b.Immediate (late-phase reaction)


A strict relationship between genetic, skin behavior, immunological factors and trigger events such as environmental, psychological, and infections may be elicited and considered to be involved in the development and severity of allergy.
