1. IgE mediated hypersensitivity

2. Allergens
Most allergic IgE responses occur on mucous membrane surfaces in response to allergens that enter the body by either inhalation or ingestion
allergens are small proteins or protein-bound substances having a molecular weight between 15,000 and 40,000,
It appears that allergenicity is a consequence of a complex series of interactions involving not only the allergen but also the
dose,
the sensitizing route, sometimes
an adjuvant, and—most important
the genetic constitution of the recipient

3. Effector mechanisms in lgE-mediated allergic reactions
Mast-cell activation has different effects on different tissues
Mast cells line external mucosal surfaces and serve to alert the immune system to local infection
inflammatory reactions by secreting pharmacological mediators such as histamine stored in preformed granules and by synthesizing prostaglandins, leukotrienes, and platelet -activating factor from the plasma membrane
Mast-cell activation has different effects on different tissues

4. IgE- unique features
Unlike other antibodies, which are found mainly in body fluids, IgE is mostly found fixed on cells that carry this receptor-mast cells in tissues and basophils in the circulation
Serum IgE levels in normal individuals fall within the range of 0.1–0.4 g/ml; even the most severely allergic individuals rarely have IgE levels greater than 1 g/ml
IgE is captured by the high-affinity Fce receptor (FceRI) in the absence of bound antigen
IgE was found to be composed of two heavy and two light chains with a combined molecular weight of 190,000
Mainly due to additional domain (CH4) contributes to an altered conformation of the Fc portion of the molecule that enables it to bind to glycoprotein receptors on the surface of basophils and mast cells
Although the half-life of IgE in the serum is only 2–3 days, once IgE has been bound to its receptor on mast cells and basophils, it is stable in that state for a number of weeks

5. IgE binding Fc receptors
There are two types of IgE-binding Fe receptor
The first, FceRI, is a high affinity receptor of the immunoglobulin superfamily that binds IgE on mast cells and basophils
Between 40,000 and 90,000 FceRI molecules have been shown to be present on a human basophil
The FcRI receptor contains four polypeptide chains: an and a chain and two identical disulfide-linked chains
FcRI interact with the CH3/CH3 and CH4/CH4 domains of the Ig molecule via the two Ig-like domains of the chain
FcRI
Each chain of the high-affinity receptor contains an ITAM, a motif also present in the Ig-/Ig- heterodimer of the B-cell receptor and in the CD3 complex of the T-cell receptor

6. ITAM motif on these three receptors interacts with protein tyrosine kinases to transduce an activating signal to the cell
Allergen mediated crosslinkage of the bound IgE results in aggregation of the FcRI receptors and rapid tyrosine phosphorylation, which initiates the process of mast-cell degranulation
The role of FcRI in anaphylaxis is confirmed by experiments conducted in mice that lack it

7. IgE binding Fc receptors
The second IgE receptor, FceRII, usually known as CD23, is a C-type lectin and is structurally unrelated to FceRI; it binds IgE with low affinity
CD23 is present on many cell types, including B cells, activated T cells, monocytes, eosinophils, platelets, follicular dendritic cells, and some thymic epithelial cells
This receptor was thought to be crucial for the regulation of IgE levels
The FcRII receptor appears to play a variety of roles in regulating the intensity of the IgE response
Interestingly, atopic individuals have higher levels of CD23 on their lymphocytes and macrophages and higher levels of sCD23 in their serum than do non-atopic individuals
The low-affinity receptor is unusual because it is oriented in the membrane with its NH2-terminus
directed toward the cell interior and its COOH-terminus directed toward the extracellular space

8. Mast cells
Mast cells were described by Ehrlich in the mesentery of rabbits and named Mastzellen ('fattened cells')
Mast cells are derived from hematopoietic stem cells but mature locally
often residing near surfaces exposed to pathogens and allergens,
such as mucosal tissues
connective tissues surrounding blood vessels
Mast cell populations in different anatomic sites differ significantly in the types and amounts of allergic mediators they contain and in their sensitivity to activating stimuli and cytokines
Mast cells also secrete a large variety of cytokines that affect a broad spectrum of physiologic, immunologic, and pathologic processes
Human mast cells are classified on the basis of their protease content
Mast cells of one class (MCT) predominantly express tryptase only, and these predominate in mucosal epithelia
whereas those of another type (MCcT) express tryptase, chymase, carboxypeptidase A, and cathepsin G and predominate in the submucosa and other connective tissues
Granule released from mast cells may contents include the short-lived vasoactive amine histamine, serine esterases, and proteases such as chymase and tryptase

9. Schematic diagrams of mechanisms that can trigger degranulation of mast cells. Note that mechanisms (b) and (c) do not require allergen; mechanisms (d) and (e) require neither allergen nor IgE; and mechanism (e) does not even require receptor crosslinkage

11. Crosslinkage of the FcRI receptors activates PTKs,
resulting in the phosphorylation of tyrosines within the ITAMs of the subunit as well as
phosphorylation of residues on the subunit and on phospholipase C
second messengers
15 s after crosslinkage of FcRI, methylation of various membrane phospholipids
increase in membrane fluidity and the formation of Ca2+ channels
Increased Ca intake and release from intracellular stores
The Ca2+ increase arachidonic acid, which is converted into two classes of potent mediators: prostaglandins and leukotrienes
the assembly of microtubules and the contraction of microfilaments helps in the release of granules

12. Several Pharmacologic Agents Mediate Type I Reactions
The mediators released during mast-cell or basophil degranulation determine the clinical manifestations
These mediators are pharmacologically active agents that act on
local tissues as well as on populations of secondary effector cells, including eosinophils, neutrophils, T lymphocytes, monocytes, and platelets