Immunostimulatory properties

Saponins are a family of glycosides (sugar derivatives) widely distributed in plants. Each saponin consists of a sugar moiety bound to a sapogenin (either a steroid or a triterpene). The immunostimulatory properties of the saponin fraction isolated from the bark of Quillaja (a tree) has been long recognized. Quil A (which consists of a mixture of related saponins) is used as an adjuvant in selected veterinary vaccines. However, its haemolytic potential precludes its use in human vaccines. Research efforts continue in an attempt to identify individual saponins (or derivatives thereof) that would make safe and effective adjuvants for use in human medicine. 

Bianco A, Hoebeke J, Godefroy S, Chaloin O, Pantarotto D, Briand JP, Muller S, Prato M, Partidos CD (2005a) Cationic carbon nanotubes bind to CpG oligodeoxynucleotides and enhance their immunostimulatory properties. J. Am. Chem. Soc. 127 58-59. 

Testing a number of DIMS in several biological systems showed differential immunostimulatory properties or other physiological effects. However, it is not always easy to explain such a variation of DIMS stimulatory capacity looking just to the primary structure. For example, changing only two nucleotides in... 

Several ILs, particularly those capable of modulating transformed cell growth, as well as those exhibiting immunostimulatory properties, enjoy significant clinical interest. As with other cytokines, the advent of recombinant DNA technology facilitates production of these molecules in quantities sufficient to meet actual/potential medical needs. 

While purified LPS displays potent immunostimulatory properties, it also induces various toxic side effects (Table 10.24), the most prominent of which is pyrogenicity. These effects render application of LPS as an adjuvant unacceptable. Both its immunostimulatory and toxic properties are mainly associated with the lipid A portion of the molecule. Attempts have been made to chemically or otherwise alter the lipid A portion in order to ameliorate the observed toxicity. 

In parallel to these initial descriptions, observations in the antisense field of study revealed that some antisense ODNs displayed sequence-specific immunostimulatory properties (Branda et al., 1993 Krieg et al., 1989, 1993 McIntyre et al., 1993 Pisetsky and Reich 1994 Tanaka et al., 1992). Exhaustive study revealed that immunostimulation by these ODNs could be attributed to the presence of CpG dinucleotides, in particular to base contexts (most importantly a hexamer) that were not restricted to a palindrome (Krieg et al., 1995) (Figure 22.1). Further, methylation of the cytosine in the CpG dinucleotide completely abrogated any immunostimulatory properties, confirming that the immunostimulatory properties of these ODNs were dependent on the presence of the unmethylated CpG dinucleotides (Krieg et al., 1995). Such immunostimulatory sequences based on unmethylated CpG dinucleotides are now known as CpG motifs. 

The immunostimulatory properties of CpG ODNs make them attractive candidates for the modulation of immune responses leading to the prevention and treatment of infectious diseases, atopic disease and malignancies. 

The field of DNA vaccines centers on the ability to deliver genetic material, coding, for desired protein antigens in the context of a mammalian expression vector (Donnelly et al., 1997). It was realized that the immunostimulatory properties observed with DNA vaccines, namely the ability to induce a Thl biased or cell mediated immune response, was attributable in part to the presence of CpG motifs within the plasmid DNA (Klinman et al., 1997). In fact, it was demonstrated that the quality of immune activation by DNA vaccines could be influenced by the deliber-ate alteration of CpG content (Krieg et al., 1998). Further, with the identification of neutralizing CpG motifs it became possible to remove any neutralizing influence from the DNA vaccine plasmids. The end result was the optimization of DNA vaccine plasmids, with respect to immune activation (Krieg et al., 1998). 

LAB are Gram-positive bacteria with cell wall components such as peptidoglycan, polysaccharide, and teichoic acid, all of which have been shown to have immunostimulatory properties. In addition to cell wall components, immunostimulatory effects were observed with antigens originated from the cytoplasms of some strains of LAB. 

The unusual indolizidinediol (21) with an cc,p y,5-unsaturated cyclopropyl side chain has been isolated from a Streptomyces species NCIB 11649. This compound shows non-selective immunostimulatory properties. Furthermore, its acetate causes a reduction in frequency of beats of cultured heart cells, an effect often seen with certain j -blocking drugs. 

Apart from their postulated immunostimulatory properties, lectin-containing extracts from mistletoe (Viscum album) have also been found to induce apoptosis [182]. The activity of the extracts depends on the... 

Sequence-dependent toxicity Palindromic sequences and dinucleotide motifs containing CpG sequences in particular, have been shown to posses potent immunostimulatory properties in rodents. Similar effects do not seem to occur in primates. 

The demonstration of leucocyte agglutination cannot therefore be taken as evidence of the ability of levamisole, or a metabolic product of it, to act as a hapten capable of conjugation to host macromolecules and able to stimulate drug-specific antibodies. Perhaps the view of Epstein et al. (1977) that the immunostimulatory properties of levamisole are responsible for a boost in pre-existing anti-leucocyte antibodies in these patients provides a partial explanation. 

Weilhammer, D.R., Blanchette, C.D., Fischer, N.O., Alam, S., Loots, G.G., Corzett, M., Thomas, C., Lychak, C., Dunkle, A.D., Ruitenberg, J.J., Ghanekar, S.A., Sant, A.J., Rasley, A. The use of nanolipoprotein particles to enhance the immunostimulatory properties of innate immune agonists against lethal influenza challenge. Biomaterials 34,10305-10318 (2013)... 

Polymers shown to possess immunostimulatory properties in the form of their degraded products are the polyiminocarbonates (Kohn et al, 1986), based on a variation of classical polycarbonates (8). The only stractural... 

Levans are synthesized in approximately all bacterial versions of fructan production, as well as being possible to produce by fracturing soybean mucilage. Levan, fructose-composed biopolymer of bacterial origin, has potential in biotechnology due to its prebiotic and immunostimulatory properties. It was suggested that the combination of levan and nutritionally important microelements in the form of NPs serves as a first step towards a novel 2 in 1 approach for food supplements to provide safe and efficient delivery of microelements for humans and support beneficial gut microbiota with nutritional oligosaccharides [68],... 

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