Hypersensitivity reactions Immune complex-mediated

Figure 6.33 The basis of type III hypersensitivity reactions. These are mediated by immune complexes formed between antigen and IgG antibodies, which accumulate in capillaries and in tissues.

Immediate hypersensitivity Hay fever, urticaria, atopic asthma Antibody-dependent cytotoxic hypersensitivity Immune complex mediated hypersensitivity (Arthus reaction)... 

Penicillins can cause all four types of hypersensitivity responses provoking type I IgE-mediated reactions such as urticaria, angioedema, asthma, and anaphylaxis type n antibody-mediated hemolytic anemia and thrombocytopenia type III immune complex-mediated serum sickness-like reactions and vasculitis and type IV T cell-mediated contact dermatitis, rashes, and other skin eruptions (refer to Chaps. 2 and 3). Table 5.1 lists clinical adverse reactions, together with their immune... 

Innnunologic Dextran 70 has been used as stabilizer in a measles-mumps-rubella (MMR) vaccine product named Morupar. This vaccine was associated with dextran-driven hypersensitivity reactions with high concentrations of dextran-spedfic IgG [43"]. The most probable mechanism is immune complex-mediated reactions caused by naturally occurring dextran-specific antibodies. Morupar was withdrawn from the market. 

Types II and III Hypersensitivity. No simple animal models are currently available to assess Type II (antibody-mediated cytotoxicity) hypersensitivity reactions. IgE antibodies and immune complexes in the sera of exposed animals can be assayed using ELISA or RIA techniques that require the use of specific antibodies to the drug. 

Most anaphylactoid reactions are due to a direct or chemical release of histamine, and other mediators, from mast cells and basophils. Immune-mediated hypersensitivity reactions have been classified as types I-IV. Type I, involving IgE or IgG antibodies, is the main mechanism involved in most anaphylactic or immediate hypersensitivity reactions to anaesthetic drugs. Type II, also known as antibody-dependent hypersensitivity or cytotoxic reactions are, for example, responsible for ABO-incompatible blood transfusion reactions. Type III, immune complex reactions, include classic serum sickness. Type IV, cellular responses mediated by sensitised lymphocytes, may account for as much as 80% of allergic reactions to local anaesthetic. 

The newer derivatives seem less likely to cause hypersensitivity reactions, perhaps because the protein adducts generated are shorter lived. All four types of hypersensitivity reaction have been observed with penicillin. Thus, high doses may cause hemolytic anemia and immune complex disease and cell-mediated immunity may give rise to skin rashes and eruptions, and the most common reactions are urticaria, skin eruptions, and arthralgia. Antipenicillin IgE antibodies have been detected consistently with an anaphylactic reaction. The anaphylactic reactions (type 1 see above), which occur in 0.004% to 0.015% of patients, may be life threatening. 

Must histamine is synthesized and stored in mast cells and basophilic granultKytes. Protein-complexed histamine is then stored in secretory granules and released by exocytosis in le.sponse to a wide variety of immune (antigen and antibody) and nonimmunc (bacterial products, xenobiotics, physical effects, and cholinergic effects) stimuli. The release of histamine as one of the mediators of hypersensitivity reactions is initiated by the interaction of an antigen-IgE com-... 

In contrast to contact hypersensitivity, tuberculin-type hypersensitivity reactions are primarily dermal and result from intradermal injections into the skin. In people that have had tuberculosis or have been exposed to the bacterium through infection or BCG immunization, a cell-mediated immune response to the bacterium develops. When small amounts of tuberculin (a complex mixture of antigenic material derived from Mycobacterium tuberculosis) are subsequently injected into the skin, a localized T cell-dependent inflammatory response develops in the dermis. Within 24-72 h of injection, individuals with prior exposure to the bacterium display a raised, red, indurated area on the skin at the injection site. The lack of a response suggests no prior exposure to the bacterium. 

Coico R, Sunshine G, and Benjamini E. Hypersensitivity Reactions Antibody-mediated (Type 11) Cytotoxic Reactions and Immune Complex (Type 111) Reactions. In Immunology, A Short Course (5th Edition). Wiley, Hoboken, NJ, 2003, pp. 215-224. 

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