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HYPERSENSITIVITY REACTIONS

Hypersensitivity refers to undesirable (damaging, discomfort-producing and sometimes fatal) reactions produced by the normal immune system Hypersensitivity reactions require a presensitized (immune) state of the host
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CLASSIFICATION
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TYPE I – IMMEDIATE, ATOPIC, ANAPHYLLACTIC TYPE II – ANTIBODY DEPENDANT TYPE III – IMMUNE COMPLEX TYPE IV – CELL MEDIATED / DELAYED TYPE OF HYPERSENSITIVITY TYPE V - STIMULATORY
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g.com 4 .Type 1: Immediate Hypersensitivity Reaction   Mediated by IgE antibody to specific antigens  Mast cells stimulated and release histamine Reaction within one hour of exposure Examples     Anaphylaxis (e. Penicillin) Urticaria Angioedema Atopic Allergy www.similima.

Type 2: Cytotoxic Antibody Reaction Mediated by IgG and IgM to specific antigens Examples  Transfusion Reaction  Rhesus Incompatibility (Rh Incompatibility)  Mycoplasma pneumoniae related cold agglutinins  Hashimoto' Thyroiditis  Good pasture's Syndrome  Delayed transplant graft rejection  www.similima.com 5 .

com 6 . Farmer's Lung) Rheumatoid Arthritis Elephantiasis (Wuchereria bancrofti reaction) Jarisch-Herxheimer Reaction Serum Sickness www.g.Type 3: Immune Complex Reaction Antigen-antibody complexes deposit in tissue  Reaction within 1-3 weeks after exposure Examples          Systemic Lupus Erythematosus Erythema Nodosum Polyarteritis nodosa Arthus Reaction (e.similima.

com 7  Examples   .similima.Type 4: Delayed-Type Hypersensitivity  Mediated by T-Lymphocytes to specific antigens   Involves major histocompatibility complex (MHC) Reaction within 2-7 days after exposure Mantoux Test (PPD) Allergic Contact Dermatitis (e.g. Nickel allergy) www.

Other allergy mediated reactions        Stimulatory Hypersensitivity Humoral antibody activates receptor sites Example: Thyrotoxicosis (TSH autoantibodies) Fas/Fas ligand-induced apoptosis Example: Stevens Johnson Syndrome T-Cell activation Example: Sulfonamide induced Morbilliform rash www.com 8 .similima.

TYPE I HYPERSENSITIVITY REACTION     Type 1 hypersensitivity is an allergic reaction provoked by re-exposure to a specific type of antigen referred to as an allergen Exposure may be by ingestion. or direct contact The difference between a normal immune response and a type I hypersensitive response is that plasma cells secrete IgE This class of antibodies binds to Fc receptors on the surface of tissue mast cells and blood basophils www. inhalation.similima. injection.com 9 .

agents which deplete cytoplasmic Ca++ suppress degranulation. in response to certain antigens (allergens). www. Mast cell degranulation is preceded by increased Ca+ + influx. ionophores which increase cytoplasmic Ca++ also promote degranulation. which is a crucial process.similima. whereas. A subsequent exposure to the same allergen cross links the cell-bound IgE and triggers the release of various pharmacologically active substances Cross-linking of IgE Fc-receptor is important in mast cell triggering.     The mechanism of reaction involves preferential production of IgE. IgE has very high affinity for its receptor on mast cells and basophils.com 10 .

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vasodilatation. edema  ECF-A (tetrapeptides)attract eosinophil and neutrophils  www.similima.kinins and vasodilatation.bronchoconstriction.Pharmacologic Mediators of Immediate Hypersensitivity  Preformed mediators in granules  Histamine . vascular permeability.com 12 . vascular permeability  Tryptase – proteolysis  Kininogenase . mucus secretion.

edema and pain PAF .same as histamine but 1000x more potent prostaglandins D2 .B4 basophil attractant leukotriene C4.Newly formed mediators     Leukotriene.similima.platelet aggregation and heparin release: microthrombi  www. D4 .com 13 .

helminthic infection.g.. etc.similima.com 14 .     Diagnostic tests for immediate hypersensitivity include skin (prick and intradermal) tests measurement of total IgE and specific IgE antibodies against the suspected allergens Total IgE and specific IgE antibodies are measured by a modification of enzyme immunoassay (ELISA) Increased IgE levels are indicative of an  atopic condition. myelomas. although IgE may be elevated in some non-atopic diseases (e.) www.

similima.Intradermal skin test with multiple positive allergen responses  www.com 15 .

similima. www.TYPE 2 HYPERSENSITIVITY REACTION Mechanism  Either IgG or IgM is made against normal self antigens as a result of a failure in immune tolerance or a foreign antigen resembling some molecule on the surface of host cells enters the body and IgG or IgM made against that antigen then cross reacts with the host cell surface.com 16 .

or C4b and discharge their lysosomes www.com 17 .similima.  The binding of these antibodies to the surface of host cells then leads to: opsonization of the host cells whereby phagocytes stick to host cells by way of IgG. C3b.

Phagocytes www. Step-1 The Fab of IgG reacts with epitopes on the host cell membrane.com Fc portion bind to the 18 .Opsonization During Type-II Hypersensitivity.similima.

www.Opsonization During Type-II Hypersensitivity.similima. Step-2 Phagocytes binding to the Fc portion of the IgG and discharge their lysosomes causing cell lysis.com 19 .

Phagocytes then bind to the Fc portion of the IgG and discharge their lysosomes.IgG reacts with epitopes on the host cell membrane. www.similima.com 20 .

similima. activation of the classical complement pathway causing MAC lysis of the cells www.com 21 .

similima.MAC Lysis During Type-II Hypersensitivity.com attack complex (MAC) then causes lysis of the cell. . Step-1 IgG or IgM reacts with epitopes on the host cell membrane and activates the classical complement pathway. Membrane 22 www.

similima. Step-2 Membrane attack complex (MAC) then causing lysis of the cell.MAC Lysis During Type-II Hypersensitivity.com 23 . www.

IgG or IgM reacts with epitopes on the host cell membrane and activates the classical complement pathway.com 24 . Membrane attack complex (MAC) then causes lysis of the cell. www.similima.

Granzymes pass through the pores and activate the enzymes that lead to apoptosis of the infected cell by means of destruction of its structural cytoskeleton proteins and by chromosomal degradation.com 25 . www. The NK cell then release pore-forming proteins called perforins and proteolytic enzymes called granzymes.   ADCC destruction of the host cells whereby NK cells attach to the Fc portion of the antibodies.similima.

ADCC-Induced Apoptosis by NK Cells During Type II Hypersensitivity.com 26 .similima. Step-1 www.

Step-2 www.similima.com 27 .ADCC-Induced Apoptosis by NK Cells During Type II Hypersensitivity.

ADCC-Induced Apoptosis by NK Cells During Type II Hypersensitivity.similima.com 28 . Step-3 www.

ADCC Destruction During Type-II Hypersensitivity www.similima.com 29 .

ADCC Apoptosis by NK Cells During Type II Hypersensitivity www.com 30 .similima.

com 31 . granulocytopenia and thrombocytopenia are such examples The reaction time is minutes to hours Type II hypersensitivity is primarily mediated by antibodies of the IgM or IgG classes and complement Phagocytes and K cells may also play a role (ADCC) www.Type II Hypersensitivity Reaction       Type II hypersensitivity affects a variety of organs and tissues The antigens are normally endogenous.similima. although exogenous chemicals (haptens) which can attach to cell membranes can also lead to type II hypersensitivity Drug-induced hemolytic anemia.

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www.com 33 .similima. Diagnostic tests include detection of circulating antibody against the tissues involved and the presence of antibody and complement in the lesion (biopsy) by immunofluorescence.

com 34 .similima. The staining pattern is normally smooth and linear. such as that seen in Good pasture's nephritis (renal and lung basement membrane) www.

pemphigus (skin intercellular protein.similima.com 35 . desmosome) www.

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