Immune response induction

The immunostimulatory effects of saponins can be observed both in vivo and/or in vitro, and may either be directed against a specific antigen induced immune response (adjuvant effect), or to a nonspecific type of immune response. Induction of an adjuvant effect always takes place in vivo, whereas nonspecific stimulation may also take place in vitro. Presently, the bidesmosidic saponins from Quillaja saponaria Molina [16], and to some degree those from Gypsophila sp. and Saponaria officinalis [42], are the only saponins with effective and confirmed antigen-specific immunomodulatory activities in vivo. However, other saponins that show immunostimulatory activity in vitro and/or in vivo are also considered herein. 

Lentivirus has shown reasonable promise for cardiac applications because it can transduce nondividing cells like cardiomyocytes (Davis et al., 2008). The sequence delivered by the lentivirus integrates into host genome, which means that transfection is stable but also introduces the risk of mutagenesis, carcinogenesis, and immune response induction (Haider et al., 2008). Another disadvantage of lentivirus is that only low titres can be prepared (Davis et al., 2008). Fmthermore, lentiviruses are less stable than other vectors and thus are more difficult to work with (Davis et al., 2008). A final drawback is that these vectors have very high efficiency in vitro (80-100%) but only up to about 30% efficiency in vivo (Davis et al., 2008). 

The field of DNA vaccination started when eukaryotic expression vectors were injected into the muscle of laboratory animals [2]. The authors observed protein expression for more than 2 months after injection and noted that no special delivery system was required to obtain this expression. Subsequently, it was demonstrated that antibodies can be induced simply by injecting plasmid DNA into the muscle of mice [3]. Subsequent studies found that the injection of expression plasmids also leads to the induction of a cytotoxic T-cell response. After injection, the DNA enters cells of the vaccinated host and the encoded gene becomes expressed. This eventually leads to the induction of a cellular cytotoxic T-cell, T-helper, and/or humoral (antibody) immune response. 

The key end result of TLR signalling is the induction of cytokines. Cytokines are proteins produced during an immune response that allow the maturation, activation and differentiation of effector cells in the immune system. The activation of NFkB and AP-1 by the MyD88 and the TREF dependent pathways leads to the production of proinflammatory cytokines such as IL-6, TNF-a and various chemokines. This pathway can also activate IRF-7 via TLR-7and TLR-9 allowing Type-I interferons to be produced. 

Inhibition of human allergic T-helper type 2 immune responses by induced regulatory T cells requires the combination of interleukin- 10-treated dendritic cells and transforming growth factor-p for their induction. Clin Exp Allergy 2006 36 1546-1555. 

Innate immune response to viral infections is predominately through interferon-alpha, -beta (IFN-a and -P) induction and activation of natural killer (NK) cells. Although viral replication can induce IFN-a and -P expression, macrophages are capable of producing and secreting cytokines which also induce the production of these type I interferons (Falk 2001). Bound IFNa and p to its receptors on NK cells increases its ability to lyse virally-infected cells. 

After activation, cytotoxic T cells emerge from lymphoid organs to infiltrate the graft and trigger the immune response. These cells have been shown to induce graft destruction via two mechanisms (1) secretion of the cytotoxic proteins perforin and granzyme B, and (2) induction of cellular apoptosis... 

The improved short-term outcomes gained from induction therapy come with a degree of risk. By using these highly immunosuppressive agents, particularly the antilymphocyte antibodies (ALAs), muronomab-CD3 (OKT-3), and the antithymocyte antibodies, the body loses much of its innate ability to mount a cell-mediated immune response, which increases the risk of opportunistic infections and cancer.7,10... 

Neutra, M.R., Pringault, E. and Kraehenbuhl, J.P. (1996) Antigen sampling across epithelial barriers and induction of mucosal immune responses. Annual Review of Immunology 14, 275-300. 

Tsuyuki, S., Tsuyuki, J., Einsle, K., Kopf, M. and Coyle, A.J. (1997) Co-stimulation through B7-2 (CD86) is required for the induction of a lung mucosal T helper cell 2 (Th2) immune response and altered airway responsiveness. Journal of Experimental Medicine 185, 1671-1679. 

Else, KJ., Hultner, L. and Grencis, R.K. (1992) Cellular immune responses to the murine nematode parasite Trichuris muris. II. Differential induction of TH-cell subsets in resistant versus susceptible mice. Immunology 75, 232-237. 

Wang, H.W., Tedla, N., Lloyd, A.R., Wakefield, D. and McNeil, P.H. (1998) Mast cell activation and migration to lymph nodes during induction of an immune response in mice. Journal of Clinical Investigation 102, 1617-1626. 

The main site of the mucosal immune system in the gut is referred to as gut-associated lymphoid tissue (GALT), which can be divided into inductive and effector sites. In the small intestine, the inductive sites are in the Peyer s patches, which consist of large lymphoid follicles in the terminal small intestine. The contact with external antibodies triggers a series of cascade events in the body based on immune response (Brandtzaeg et al., 1999). 

Induction of Immune Responses Using Amphiphilic Poly(amino acid)... 

Fig. 12 Induction of immune responses by nanoparticle-based vaccine...

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