Immune response modification

There are a number of practical problems involved with using polysaccharides as vaccines as there are frequently too many different chemotypes for it to be practicable to prepare a vaccine. In some cases a limited number of serotypes are the dominant cause of infection and it may then be possible to produce vaccines. A major problem is the poor immune response elicited by polysaccharide antigens, which may in some cases be improved by chemical modification. This is (fie case for vaccines for Haemophilus influenzae type b (a causative agent of meningitis), where the antigenicity of the polysaccharide can be increased by coupling to proteins. 

Some synthetic carriers actually are designed to have low immunogenicity on their own to minimize the potential for antibody production against them. When a hapten is coupled to these molecules, the immune response is directed principally toward the modification, not at the carrier. This design approach guides most of the immune response toward the desired target and minimizes the production of carrier-specific antibodies. 

Irey, N.S., Drug adverse reaction reports related to immunotoxicity, in Inadvertent Modification of the Immune Response The Effects of Foods, Drugs, and Environmental Contaminants, Asher, I.M., Ed., US Food and Drug Administration, Washington, D.C., 1978, p. 140. 

Meri, S. andBaumann, M., Proteomics posttranslational modifications, immune responses and current analytical tools, Biomol. Eng., 18, 213, 2001. 

Dogra RK, Khanna S, Shukla L, et al. 1987. Modification of the immune response in rats by di-octyl phthalate. Industrial Health 25 97-101. 

About 10-20% of all transmembrane proteins that are targeted to the ER and subsequently enter the secretory pathway are subject to post-translational modification with glycosylphosphatidyl-inositol (GPI). Proteins bearing the GPI anchor are involved in signal transduction, immune response, cancer cell invasion, and metastasis and the pathobiology of trypanosomal parasites. The structure of the GPI anchor has been analyzed for mammals, protozoa, and yeast. The general structure of the glycolipid structure is shown in Scheme 4. 

PUVA is most useful for the treatment of severe psoriasis. Early (patch and plaque) stage cutaneous T-cell lymphoma (CTCL) also responds to PUVA therapy. In addition, patients in advanced stages of CTCL have been treated with a modification of PUVA known as extracorporeal photopheresis. In this therapy, blood from a CTCL patient who has taken psoralen is exposed to UVA light and returned to the patient. Lymphocytes are altered or destroyed by the treatment, and theoretically, the return of these abnormal cells triggers an immune response directed against certain lymphocyte surface antigens. The effectiveness of this modality appears to be variable. 

Fraker and Aust. 1980. The effect of polybrominated biphenyls on the immune response of BALB/c mice. In Asher IM,ed. Inadvertent modifications of the immune response the effect of foods, drugs, and environmental contaminants. Proceedings of the 4 FDA Science Symposium. HHS Publication no. (FDA) 80-1074, 270-271. 

Antigens not only induce an immune response, but will also react with antibodies existing in a living organism. These two properties are different. Small molecules like pesticides are not able to induce the production of antibodies. They can only react with antibodies already present. They are called haptens. To generate antibodies specific to a hapten, haptens must be covalently bonded to a protein (e.g. BSA Bovine Serum Albumin) or polysaccharide. Therefore, the hapten must have reactive sites. On the other hand, this modification in the structure must not influence the specificity of the antibodies that will be produced. 

A modification of the immune response could be responsible for the antiviral and anticancer activity of saponins. 

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