HYPERSENSITIVITY Program : M.Sc Biochemistry Course title : Immunology Unit : IV Staff in-charge : Prof. T. Antony Diwakar Chandran Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

Different types of cells and mediators are involved . Hypersensitivity refers to undesirable (damaging, discomfort producing and sometimes fatal) reactions produced by the normal immune system. Hypersensitivity reactions require a pre-sensitized (immune) state of the host. Hypersensitivity reactions can be divided into four types: type I, type II, type III and type IV, based on the mechanisms involved and time taken for the reaction. Frequently, a particular clinical condition (disease) may involve more than one type of reaction. The duration of the reactions of the above differ ranging from several minutes to days. Different types of cells and mediators are involved . Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

Department of Biochemistry, St Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

Department of Biochemistry, St Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

ALLERGENS Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

Department of Biochemistry, St Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

REAGINIC ANTIBODY (IGE) The existence of a human serum factor that reacts with allergens was first demonstrated by K. Prausnitz and H. Kustner in 1921. The local wheal and flare response that occurs when an allergen is injected into a sensitized individual is called the P-K reaction. Because the serum components responsible for the P-K reaction displayed specificity for allergen, they were assumed to be antibodies, but the nature of these P-K antibodies, or reagins, was not demonstrated for many years. Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

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. These low levels made physiochemical studies of IgE difficult; it was not until the discovery of an IgE myeloma by S. G. O. Johansson and H. Bennich in 1967 that extensive chemical analysis of IgE could be undertaken. IgE was found to be composed of two heavy and two light chains with a combined molecular weight of 190,000. The higher molecular weight as compared with IgG (150,000) is due to the presence of an additional constant-region domain. This 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. Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

Mast-cells Mast-cell precursors are formed in the bone marrow during hematopoiesis and are carried to virtually all vascularized peripheral tissues, where they differentiate into mature cells. Mast cells are found throughout connective tissue, and in other tissues :skin, for example, contains 10,000 mast cells per mm3. Electron micrographs of mast cells reveal numerous membrane-bounded granules distributed throughout the cytoplasm, which, like those in basophils, contain pharmacologically active mediators. 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 . Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

Department of Biochemistry, St Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

Fc RECEPTORS Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

INDUCED ANAPHYLAXIS Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

SIGNAL TRANSDUCTION Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

MEDIATORS Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

Histamine initially binds to specific receptors on various target cells. Three types of histamine receptors— designated H1, H2, and H3—have been identified; these receptors have different tissue distributions and mediate different effects when they bind histamine. Most of the biologic effects of histamine in allergic reactions are mediated by the binding of histamine to H1 receptors. This binding induces contraction of intestinal and bronchial smooth muscles, increased permeability of venules, and increased mucus secretion by goblet cells. Interaction of histamine with H2 receptors increases vasopermeability and dilation and stimulates exocrine glands. Binding of histamine to H2 receptors on mast cells and basophils suppresses degranulation; thus, histamine exerts negative feedback on the release of mediators. Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

Department of Biochemistry, St Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

Department of Biochemistry, St Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

Department of Biochemistry, St Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

RIST This highly sensitive technique, based on the radioimmunoassay, can detect nanomolar levels of total IgE. The patient’s serum is reacted with agarose beads or paper disks coated with rabbit anti-IgE. After the beads or disks are washed, 125I-labeled rabbit anti- IgE is added. The radioactivity of the beads or disks, measured with a gamma counter, is proportional to the level of IgE in the patient’s serum. Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

RAST (RAST) detects the serum level of IgE specific for a given allergen. The allergen is coupled to beads or disks, the patient’s serum is added, and unbound antibody is washed away. The amount of specific IgE bound to the solid-phase allergen is then measured by adding 125I-labeled rabbit anti-IgE, washing the beads, and counting the bound radioactivity . Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

Treatment Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

TYPE II HYPERSENSITIVITY (cytotoxic) Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

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Blood transfusion reactions Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

Department of Biochemistry, St Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

Department of Biochemistry, St Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

Department of Biochemistry, St Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

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Type III Hypersensitivity Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

The reaction of antibody with antigen generates immune complexes The reaction of antibody with antigen generates immune complexes. Generally this complexing of antigen with antibody facilitates the clearance of antigen by phagocytic cells. In some cases, however, large amounts of immune complexes can lead to tissue-damaging type III hypersensitive reactions. The magnitude of the reaction depends on the quantity of immune complexes as well as their distribution within the body. When the complexes are deposited in tissue very near the site of antigen entry, a localized reaction develops. Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

Type III hypersensitive reactions develop when immune complexes activate the complement system’s array of immune effector molecules C3a, C5a, and C5b67 are also chemotactic factors for neutrophils, which can accumulate in large numbers at the site of immune-complex deposition. Larger immune complexes are deposited on the basement membrane of blood vessel walls or kidney glomeruli, whereas smaller complexes may pass through the basement membrane and be deposited in the subepithelium. The type of lesion that results depends on the site of deposition of the complexes. Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

Department of Biochemistry, St Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

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Arthus reaction Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

Arthus reaction Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

Serum sickness Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

Factors affecting the persistence of immune complexes in the blood stream. Size of the complex Complexes made up of Ig M are large complexes when compared with that made of other globulins. Presence of carbohydrate side chains If the carbohydrate side chains are present in the deeper area, of the protein structure , they could not be recognized by the complement proteins. Concentration of complement one of the main functions of complement proteins is to solubilize the immune complexes. Complement deficiency may cause prolonged existence of complement in the system. Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

Hydrodynamic properties of blood Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

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Type IV hypersensitivity (delayed type) Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

When some subpopulations of activated TH cells encounter certain types of antigens, they secrete cytokines that induce a localized inflammatory reaction called delayed-type hypersensitivity (DTH). The reaction is characterized by large influxes of nonspecific inflammatory cells, in particular, macrophages. This type of reaction was first described in 1890 by Robert Koch, who observed that individuals infected with Mycobacterium tuberculosis developed a localized inflammatory response when injected intradermally with a filtrate derived from a mycobacterial culture. He called this localized skin reaction a “tuberculin reaction.” The hallmarks of a type IV reaction are the delay in time 48- 72 hours required for the reaction to develop and the recruitment of macrophages as opposed to neutrophils, as found in a type III reaction.Macrophages are the major component of the infiltrate that surrounds the site of inflammation. Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

Department of Biochemistry, St Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

Department of Biochemistry, St Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

Department of Biochemistry, St Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

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Contact dermatitis Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002

1.Immunology by Janis Kuby References 1.Immunology by Janis Kuby 2. Cell and molecular Immunology by Abbas and Litchman Department of Biochemistry, St.Joseph's College(Autonomous),Tiruchirappalli-620002