Toxins tetanus, immunization

Tetanus-diphtheria toxin Tetanus immune globulin... 

Tetanus immunoglobulin is an example of an antibody preparation used to induee passive immunization against a mierobial toxin. Tetanus (lockjaw) is an infectious disease caused by the bacterium, Clostridium tetani. Bacterial spores can commonly contaminate surface wounds and the resulting bacterial cells produce a toxin as they multiply. The toxin interferes with normal neurological function, particularly at neuromuscular junctions. The result is spasmodic contraction of muscles and, if untreated, mortality rates are high. Treatment with antibiotics and anti-toxin, however, is highly effective if administered promptly. 

Schiavo G, Papini E, Genna G, Montecucco C (1990) An intact interchain disulfide bond is required for the neurotoxicity of tetanus toxin. Infect Immun 58 4136 11 Scott AB, Magoon EH, McNeer KW, Stager DR (1989) Botulinum treatment of strabismus in children. Trans Am Ophthalmol Soc 87 174-180 discussion 180 1 Scott D (1997) Phospholipase A2 structure and catalytic properties. In Kini R (ed) Venom phospholipase A2 enzymes structure, function and mechanism. John Wiley Sons, Chichester, p 97-128. 

Mesnage, S., Weber-Levy, M., Haustant, M., Mock, M., Fouet, A. (1999). Cell surface-exposed tetanus toxin fragment C produced by recombinant Bacillus anthracis protects against tetanus toxin. Infect. Immun. 67 4847-50. 

Triacelluvax [combination vaccine containing recombinant (modified) pertussis toxin] Chiron immunization against diphtheria, tetanus and pertussis 1999 (EU)... 

Tetanus immune globulin is an immune globulin, which directly neutralizes toxin excreted by Clostridium tetani. It is indicated as a passive, transient protection against tetanus in any person that may be contaminated with tetanus spores when (1) a patient s personal history of immunization with tetanus toxoid is unknown or uncertain, (2) a person received less than 2 a prior doses of... 

Tetanus-diphtheria toxin and a broad spectrum antibiotic Tetanus-diphtheria toxin and tetanus immune globulin... 

Human tetanus immune globulin (TIG), 3000-5000 lU administered IM, will neutralize circulating toxin but has no effect on toxin already fixed to neurons. TIG should be given as early as possible to a patient with suspected tetanus and to persons with a fresh wound but possibly inadequate prior immunization. 

B. Human tetanus immune globulin (antitoxin) provides passive immunity by neutralizing circulating tetanospasmin and unbound toxin in a wound. It does not have an effect on toxin that is already bound to neural tissue, and tetanus antibody does not penetrate the blood-brain barrier. 

Since these vaecines are imable to evoke a natural infection profile with respeet to the release of antigen they must be administered on a number of occasions. Immunity is not complete until the course of immunization is complete and, with the exeeption of toxin-dominated diseases (diphtheria, tetanus) where the immimogen is a toxoid, will never match the performance of live vaccine delivery. Specificity of the immrme resporrse generated in the patient is initially low. This is particularly the case when the vaeeine is composed of a relatively crude cocktail of killed cells where the immime response is direeted only partly towards antigenic components of the cells that are assoeiated with the infeetion process. This increases the possibility of adverse reaetions in the patient. 

Compared to people in a noncontaminated area, plasma IgG levels were also significantly decreased in proportion to increasing plasma levels of TCDD in a cohort exposed in an industrial accident in Seveso, Italy.118 There was no effect on IgM or IgA levels, or on complement levels IgE was not measured. In separate studies, in vitro exposure to TCDD enhanced the spontaneous production of IgE by B cells isolated from atopic but not non-atopic individuals, but did not affect the levels of other isotypes.119 Other recent studies have reported small changes in immune cells from individuals exposed occupationally to PHAH.120121 For example, compared to unexposed controls, a cohort of men exposed occupationally to TCDD had diminished IFNy production in a recall response to tetanus toxin, while IFNy production following polyclonal activation was unaffected.120 This observation is consistent with mouse studies, in which antigen-specific responses are highly suppressed by TCDD, but mitogen-driven T cell responses are less susceptible to impairment.83 88122123... 

Toxoid A modified bacterial toxin that has been rendered nontoxic (commonly with formaldehyde) but retains the ability to stimulate the formation of antitoxins (antibodies) and thus producing an active immunity. Examples include Botulinum, tetanus, and... 

Another example that can be included in the subunit vaccine class is the use of bacterial toxoids. Many bacteria produce toxins which play an important role in the development of the disease caused by a particular organism. Thus, vaccines against some agents, for example tetanus and diphtheria, consist of the toxin inactivated with formaldehyde conjugated to an adjuvant. Immunization protects from disease by stimulating antitoxin antibody which neutralizes the effects of the toxin. 

Although the serum of animals immunized with small amounts of toxins has been used for many years to help people recover from diphtheria or to provide protection against snake or scorpion venom, there have been other situations where a specific antibody was needed in a concentrated form. Unfortunately, there were limits to what animal antibodies could do. First, the animal serum preparations, even with repeated injections, were mixtures of antibodies—not collections of many of the same antibody. That is just the way the immune system works in animals, including humans. In addition, there was always the danger of taking the serum from a diseased animal remember the case of Jim, the horse with tetanus ... 

Tetanus antitoxin is routinely administered as part of the management of tetanus-prone wounds. The antibody preparation is purified from pooled serum/plasma of human donors who have been immunized with tetanus toxin. 

Tetanus vaccines Toxoid formed by formaldehyde treatment of toxin produced by Clostridium tetani Active immunization against tetanus... 

Another vaccine protein that has recently been produced in tobacco chloroplasts is the Fragment C domain of tetanus toxin (TetC). TetC is a nontoxic 47 kDa polypeptide that can induce an immune response upon... 

The history of the development of antitoxins in combating bacterial infection dates back to the early beginnings of organized bacteriology. Belrring was tile first to show that animals that were immune to diphtheria contained, in their serum, factors which were capable of neutralizing the poisonous effect of the toxins derived from the diphtheria bacillus. While this work was earned out in 1890, prior to many of the great discoveries of mass immunization, and much later the antibiotics, there yet remains a place for antitoxins in medical treatment or prophylaxis for some diseases, such as tetanus and botulism,... 

Historically, antibodies have been obtained from the serum of animals. The serum contains a mixture of polyclonal antibodies. In 1890, Emil Behring immunized rabbits and mice against tetanus and diphtheria and reported that the antitoxin serum could protect against a lethal dose of the toxin. Since then, antisera have been used to protect from pathogens and toxins, but serum sickness was a major drawback for their clinical use. Antisera may produce immune responses, which could cause severe allergic reactions, and may even lead to anaphylactic shock and death. 

The authors also demonstrated that low-frequency ultrasound acts as a transcutaneous immunization adjuvant that eliminates the requirement of toxins to elicit an immune response. Delivery of as little as 1.3 p.g of tetanus toxoid by low-frequency ultrasound generated an immune response comparable to that induced by 10 pg subcutaneous injection. 

Benzene also affects functional immune responses, as indicated by decreased resistance to infectious agents. Pre-exposure to benzene at >30 ppm for 5-12 days increased the bacterial counts in mice on day 4 of infection with Listeria monocytogenes (Rosenthal and Snyder 1985). Recovery of the immune system was noted on day 7. The effects did not occur at 10 ppm. In addition, a concentration-dependent statistically significant depression was noted in T- and B-lymphocyte populations from day 1 through day 7 at 30 ppm and above. B-cells were more sensitive to benzene than were T-cells on a percentage-of-control basis. This indicates a benzene-induced delay in immune response to L. monocytogenes. Concentrations of 200 or 400 ppm for 4-5 weeks (5 days per week) suppressed the primary antibody response to tetanus toxin in mice, but there was no effect at 50 ppm (Stoner et al. 1981). In another intermediate-duration exposure study, no changes were noted in the numbers of splenic B-cells, T-cells, or... 

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