Serum sickness type responses

Much information can be gained from in-life physiological measurements such as blood pressure, electrocardiograms, body temperature, and respiratory rate. When the number of studies is reduced due to the lack of appropriate species and the potential for development of neutralizing antibodies, as much information as possible should be obtained from the few studies that are conducted. In-life measurements assume more importance in these cases. When the product is likely to contain proteins that may cause acute serum sickness type responses and pyrogens, measurements of blood pressure, body temperature, and respiratory parameters are especially important. 

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 major adverse reactions to the penicillins are hypersensitivity responses. Manifestations of hypersensitivity inclnde nrticaria, angioedema, and anaphylaxis (type 1 reaction) hemolytic anemia (type 11 reaction) interstitial nephritis, vascnlitis, and serum sickness (type 111 reaction) and contact dermatitis or Stevens-Johnson syndrome (type IV reaction). A maculopapular rash occnrs late in the treatment course of 2% to 3% of patients receiving a penicillin drug. Once a patient has had a hypersensitivity response to a penicillin, it is probable, bnt not certain, that a reaction will occur with exposure to the same penicillin or to any other penicillin. Intradermal skin tests can predict whether a patient is at risk for developing a hypersensitivity reaction to the penicillins. If the resnlts are positive, penicillins should generally be avoided. 

Somewhere in the mosaic of atherosclerosis, vascular sensitivity and reaction resembling an allergic response may occur. Hypertension of renal origin may be paralleled by the contribution of some component by the kidney (or by some sources excited by the hypertension or Injured kidney) that causes a predisposition of the arterial wall toward atherosclerosis. Vascular Injury of the "serum sickness" type from vascular... 

T cells control these learned responses and decide which tools to use in the reaction. Sometimes they choose several different tools at once, and multiple reactions ensue, such as when a person becomes sensitized to penicillin and has not only anaphylaxis but hemolytic anemia and serum sickness. There are different types of T cells, and they communicate either directly with other cells or by chemical messages called cytokines. The pattern of cytokines released is one way T cells have of determining which kind of response will occur. They are broadly called Thl andTh2 responses, with Thl mostly responding to infections and Th2 often producing allergy or asthma. 

Immunologic reactions to drugs resulting in serum sickness are more common than immediate anaphylactic responses, but type II and type III hypersensitivities often overlap. The clinical features of serum sickness include urticarial and erythematous skin eruptions, arthralgia or arthritis, lymphadenopathy, glomerulonephritis, peripheral edema, and fever. The reactions generally last... 

Most subjects give immediate asthmatic reactions some give non-immediate reactions and some give both. There is suggestive evidence of the presence of antibodies in other immunoglobulin classes which might be responsible for type III reactions such as the serum-sickness-like reactions induced by repeated injections of platinum salts (Levene and Calnan 1971). 

Allergy a hypersensitivity of the immune apparatus s pathological immune reaction induced either by antibodies (immediate hypersensitivity) or by lymphoid cells (delayed type A.). Unlike the delayed type, immediate hypersensitivity can be passively transmitted in the serum. Symptoms of immediate hy-peisensitivity begin shortly after contact and decay rapidly, but delayed type symptoms do not attain a maximum for 24-48 hours then decline slowly over days or weeks Examples of immediate type A. are anaphylaxis the Arthus reaction and serum sickness. The best known A., anaphylaxia, can occur as a local (cutaneous) reaction (e.g. a rash with blisters) or as a systemic reaction (anaphylactic shock). Asthma, hay fever and nettle rashes are also examples of local anaphylactic reactions which are induced by reagins (see Immunoglobulins IgE). Only primates can be sensitized by injection with human reagins. An example of delayed type A. is the tuberculin reaction, which is based on a cellular immune response. 

Type in hypersensitivity is mediated by soluble immune complexes mostly involving IgG antibodies. Drug-induced serum sickness-like reaction is the prototype example of type III drug hypersensitivity. Hypersensitivity vascu-Ms is another example of a type III hypersensitivity response induced by drugs. 

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... 

Reactions, both immune and innate and to human as well as foreign proteins, may occur to mAbs. Acute reactions caused by a number of different mechanisms have been reported. These reactions include true, type I anaphylaxis, delayed reactions, anaphylactoid responses, serum-sickness-... 

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