Human immune response to materials

Interpretation of the results is again a problem. Tests using home made monoclonal antibodies are suspect until the antisera is made available to other investigators for conformation. The use of well characterized antisera from companies which supply to others is better at this stage. Since the tissue section is examined and scored by an observer, the data from these studies are not really available for analysis by the reader. Computerized image analysis techniques are still not widely used. Thus, in evaluating the results, possible bias of the investigator must be taken into account. 

Detection of immune responses to haptens is the same as that described above, but there are some special techniques now being used. A hapten-carrier complex can be prepared in vitro by combination in solution with a large protein such as albumin or a smaller molecule such as glutathione. These can then be used to coat a solid substrate. Alternatively, the protein carrier can be coated onto a substrate, the hapten added, and then the assay performed. This probably increases the amount of hapten that is available for antibody binding and minimizes that which is lost in the tertiary folding of the protein. 

The use of chemically defined synthetic polymers is associated with minimal human immune responses. These materials are based on carbon, hydrogen, nitrogen and oxygen which are basic building blocks of the biological system. Thus the generation of antigenic material would be unlikely. Nevertheless, there are some polymeric materials with additional chemical moieties that are of concern. 

There is abundant lay press comment and little scientific material on this topic. It is apparent that there can be binding of silicone to foreign protein with stimulation of the immune response. The use of a simple hapten test, as described in section 4.5, has added greatly to our knowledge of this. It is also apparent that silicone gel is a potent adjuvant enhancing immune responses to unrelated materials. Whether this is of relevance to the use of gel filled implants remains unknown. The possible stimulation of related and unrelated immune responses remain a major concern in the use of these materials. 

This is a complex group of polymers. Their propensity to stimulate an inunune response is very small since there are few molecular groups which would be perceived as foreign by the host, perhaps explaining why clinical immune responses to polyurethanes have not been reported. 

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Any material proposed for implantation, whether for cell transplantation or some other application, must be biocompatible i.e. it must not provoke an adverse response from the host s immune system. If this goal is not met the implant may be rejected. To this end it is important that the material be easily sterilized either by exposure to high temperatures, ethylene oxide vapor, or gamma radiation. A suitable material must therefore remain unaffected by one of these three techniques. However, biocompatibility is not simply a question of sterility. The chemistry, structure, and physical form of a material are all important factors which determine its biocompatibility. Although our understanding of the human immune system is advancing rapidly, it is not yet possible to predict the immune response to a new material. This can only be determined by in vivo experiments. 

The viruses responsible for AIDS are human immunodeficiency virus 1 and 2 (HIV 1 and HIV 2) Both are retroviruses, meaning that their genetic material is RNA rather than DNA HI Vs require a host cell to reproduce and the hosts m humans are the T4 lymphocytes which are the cells primarily responsible for inducing the immune system to respond when provoked The HIV penetrates the cell wall of a T4 lymphocyte and deposits both its RNA and an enzyme called reverse transcriptase inside There the reverse transcriptase catalyzes the formation of a DNA strand that is complementary to the viral RNA The transcribed DNA then serves as the template from which the host lymphocyte produces copies of the virus which then leave the host to infect other T4 cells In the course of HIV reproduction the ability of the T4 lymphocyte to reproduce Itself IS compromised As the number of T4 cells decrease so does the body s ability to combat infections... 

In the last decade, numerous new techniques have been developed for the detection and quantitation of immune complex material in tissue and biological fluids. In many respects, clinical studies using these techniques have substantiated the primary pathogenic role of immune complexes in a variety of human diseases. At the same time, these studies have reaffirmed the notion that immune complexes occur frequently in the course of an immune response or as an epiphenomenon unrelated to pathogenesis, and that, despite the presence of immune complexes, typical clinical manifestations of immune complex disease may be an unusual event. 

ISO 10993 testing is intended to evaluate materials such as metals and polymers that essentially do not interact directly with the human immune system. However, the presence of an antibody on the device surface introduces the potential for cross-species reactions that may not be indicative of performance in humans. These interactions may affect some or all ISO 10993 in vivo tests. For example, the duration of chronic toxicity testing may be limited based on induction of immune responses or carcinogenicity studies may not be appropriate based on the specific product attributes of the antibody. 

More subjects are necessary for sensitization studies in humans than in animal studies because of the larger variation in immune responses and the need to use lower concentrations of the test material in human exposure. Usually, the sensitization of a material is assessed in a preliminary study with 20-25 subjects, and then expanded to a main study with up to 200 subjects. The sample size of test subjects in the main study must be large enough so that the results are valid for the population for which the preparation is intended. It may be of interest to use a particular component at a level 10 times the concentration in the finished product for induction. For the challenge dose, a nonirritating concentration should be used. In addition, the test conditions should reproduce the actual use of the final product, that is, the materials tested should contain all of the ingredients. In general, sensitization procedures are similar to the procedures described above ... 

Smith CL, Baker CJ, Anderson DC, Edwards MS Role of complement receptors in opsonophago-cytosis of group B streptococci by adult and neonatal neutrophils. J Infect Dis 1990 162 489-495. Vecchiarelli A, Retini C, Casadevall A, Monari C, Pietrella D, Kozel TR Involvement of C3a and C5a in interleukin-8 secretion by human polymorphonuclear cells in response to capsular material of Cryptococcus neoformans. Infect Immun 1998 66 4324--4330. 

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