SEMINAR REPORT

HYPERSENSITIVITY

SUBMITTED TO Dr.RAVI KANTT SINGH (Associate professor) SUBMITTED BY SAVITA SHARMA B.TECH IV Yr 0914354051 IMS ENGINEERING COLLEGE ,GHAZIABAD

ACKNOWLEDGE:
I would like to express my deep gratitude to my supervisor, for his guidance, suggestion and support throughout the seminar period. He has been of tremendous help right from deciding of the work domain to the completion of the report. His constructive criticism of the approach to the problem and the result obtained during the course of this work has helped me to a great extent in bringing work to its present shape.

CONTENT:
1) Acknowledgement 2) Introduction 3) Coomb classification 4) Type 1 hypersensitivity 5) Type II hypersensitivity 6) Type III hypersensitivity 7) Type IV hypersensitivity 8) Summary 9) References

INTRODUCTION:
Hypersensitivity refers to undesirable (damaging, discomfort producing and sometimes fatal) reactions produced by the normal immune system. Frequently, a particular clinical condition (disease) may involve more than one type . The ability of the immune respond inappropriately to antigenic challenge was recognized early in this century. Two French scientists, Paul Portier and Charles Richet, investigated the problem of bathers in the Mediterranean reacting violently to the stings of Portuguese Man of War jellyfish Portier and Richet concluded that the localized reaction of the bathers was the result of toxins.To counteract this reaction, the scientists experimented with the use of isolated jellyfish toxins as vaccines. Portier and Richet injected dogs with the purified toxins, followed later by a booster of toxins. Instead of reacting to the booster by producing antibodies against the toxins, the dogs immediately reacted with vomiting, diarrhea, asphyxia, and, in some instances, death. Portier and Richet coined the term anaphylaxis, loosely translated from Greek to mean the opposite of prophylaxis, to describe this overreaction. Richet was subsequently awarded the Nobel Prize in Physiology or Medicine in 1913 for his work on anaphylaxis Coombs proposed a classification scheme in which hypersensitive reactions are divided into four types. Three types of hypersensitivity occur within the humoral branch and are mediated by antibody or antigen-antibody complexes: IgE-mediated (type I), antibody-mediated (type II), and immune complexmediated (type III). A fourth type of hypersensitivity depends on reactions within the cell-mediated branch, and is termed delayed-type hypersensitivity, or DTH (type IV).

Type I Hypersensitivity It is also known as immediate or anaphylactic hypersensitivity. The reaction may involve skin (urticaria and eczema), eyes (conjunctivitis), nasopharynx (rhinorrhea, rhinitis), bronchopulmonary tissues (asthma) and gastrointestinal tract (gastroenteritis). The reaction may cause from minor inconvenience to death. The reaction takes 15-30 minutes from the time of exposure to the antigen. Sometimes the reaction may have a delayed onset (10-12 hours). Immediate hypersensitivity is mediated by IgE. The primary cellular component in this hypersensitivity is mast cell or basophil. The reaction is amplified and/or modified by platelets, neutrophils and eosinophils. A biopsy of the reaction site demonstrates mainly mast cells and eosinophils. The mechanism of reaction involves preferential production of IgE, in response to certain antigens, allergens (Figure 1). IgE has very high affinity for its receptor on mast cells and basophils. A subsequent exposure to the same allergen cross links the cell-bound IgE and triggers the release of various pharmacologically active substances (Figure 1). Cross-linking of IgE Fc-receptor is important in mast cell triggering. Mast cell degranulation is preceded by increased Ca++ influx, which is a crucial process; ionophores which increase cytoplasmic Ca++ also promote degranulation, whereas, agents which deplete cytoplasmic Ca++ suppress degranulation. The agents released from mast cells and their effects . Mast cells may be triggered by other stimuli such as exercise, emotional stress, chemicals (e.g., photographic developing medium, calcium ionospherses

TREATMENT : Antihistamines Block H1 and H2 receptors on target cell .Cromolyn sodium Blocks Ca2+ influx into mast cells .Theophylline lead prolongs high cAMP levels in mast cells by inhibiting phosphodiesterase, which cleaves cAMP to 5-AMP

echanisf action of some drugs used to treat type I hypersensitivity

Type II Hypersensitivity It is also known as cytotoxic hypersensitivity and may affect a variety of organs and tissues. The antigens are normally endogenous, although exogenous chemicals (haptens) which can attach to cell membranes can also lead to type II hypersensitivity. Drug-induced hemolytic anemia, granulocytopenia and thrombocytopenia are such examples. The reaction time is minutes to hours. It is primarily mediated by antibodies of IgM or IgG class and complement (Figure 2). Phagocytes and K cells may also play a role (ADCC). The lesion contains antibody, complement and neutrophils. Diagnostic tests include detection of circulating antibody against tissues involved and the presence of antibody and complement in the lesion (biopsy) by immunofluorescence. The staining pattern is normally smooth and linear, such as that seen in Goodpastures nephritis (renal and lung basement membrane) and pemphigus (skin intercellular protein, desmosome). Treatment involves anti-inflammatory and immunosuppressive agents

Type III Hypersensitivity It is also known as immune complex hypersensitivity. The reaction may be general (e.g., serum sickness) or may involve individual organs including skin (e.g., systemic lupus erythematosus, Arthus reaction), kidneys (e.g., lupus nephritis), lungs (e.g., aspergillosis), blood vessels (e.g., polyarteritis), joints (e.g., rheumatoid arthritis) or other organs. This reaction may be the pathogenic mechanism of diseases caused by many microorganisms. The reaction may take 3-10 hours after exposure to the antigen (as in Arthus reaction). It is mediated by soluble immune complexes. They are mostly of IgG class, although IgM may also be involved. The antigen may be exogenous (chronic bacterial, viral or parasitic infections), or endogenous (nonorgan specific autoimmunity: e.g., systemic lupus eythematosus, SLE). The antigen is soluble and not attached to the organ involved. Primary components are soluble immune complexes and complement (C3a, 4a and 5a). The damage is caused by platelets and neutrophils . Diagnosis involves examination of tissue biopsies for deposits of Ig and complement by immunofluorescence. . Presence of immune complexes in serum and depletion in complement level

are also diagnostic. .

Type IV Hypersensitivity It is also known as cell mediated or delayed type hypersensitivity. The classical example of this hypersensitivity is tuberculin (Montoux) reaction which peaks 48 hours after the injection of antigen (PPD or old tuberculin). The lesion is characterized by induration and erythema. Type IV hypersensitivity is involved in the pathogenesis of many autoimmune and infectious diseases (tuberculosis, leprosy, blastomycosis, histoplasmosis, toxoplasmosis, leishmaniasis, etc.and granulomas due to infections and foreign antigens. Another form of delayed hypersensitivity is contact dermatitis (poison ivy, chemicals, heavy metals, etc.) in which the lesions are more papular. Type IV hypersensitivity can be classified into three categories depending on the time of onset and clinical and histological presentation

fig: comparison of hypersensitivity

References 1. Gell PGH, Coombs RRA, eds. Clinical Aspects of Immunology. 1st ed. Oxford, England: Blackwell; 1963. 2. Black, CA. Delayed Type Hypersensitivity: Current Theories with an Historic PerspectiveDermatol. Online J. (May 1999) 5(1):7 athttp://dermatology.cdlib.org/DOJvol5num1/reviews/black.html 3. http://emedicine.medscape.com/article/136118-overview 4. Table 5-1 in:Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson (2007). Robbins Basic Pathology. Philadelphia: Saunders. . 8th edition. 5. Rajan TV (July 2003). "The Gell-Coombs classification of hypersensitivity reactions: a reinterpretation".