Induction of an Immune Response

After an antigen (a non-self molecular entity) has entered the body, it is recognized by the cells of the immune system. An important step in eliciting an efficient immune response to an 

7 Vascular Endothelium in Inflamed Tissue as a Target for Site Selective Delivery of Drugs 

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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 mechanism most commonly invoked to explain the association of infection with autoimmune disease is molecular mimicry that is, the concept that antigens (or more properly, epitopes) of the microorganism closely resemble self-antigens.50 The induction of an immune response to the microbial antigen thus results in cross-reactivity with selfantigens and the induction of autoimmunity. Although epitope specific cross-reactivity has been shown in some animal models,48,51 53 molecular mimicry is clearly demonstrated to be the causative mechanism in few, if any, human diseases.3 54,55... 

The guinea pig maximization test (GPMT) is a preferred method for the detection of skin sensitizers. It belongs to the class of adjuvant-tests, where the substance will be applied in Freund s complete adjuvant (FCA). The test is based on the possible induction of an immune response of the skin during an induction period (at least 1 week). This pretreatment of the subject will eventually result in a hypersensitive reaction during a further exposure, the so-called challenging phase. 

Fernandes I, et al. Synthetic lipopeptides incorporated in liposomes in vitro stimulation of the proliferation of murine splenocytes and in vivo induction of an immune response against a peptide antigen. Mol Immunol 1997 34 569. 

Chemicals and pharmaceuticals may be tested for their capacity to induce skin sensitization [49]. The potency of a xenobiotic or pharmaceutical compound to induce delayed type hypersensitivity (DTH) or contact dermatitis (CD) may be tested in the so called local lymph node assay (LENA) in which the induction of an immune response in lymph nodes is determined after local (skin) exposure [49-51]. The induction of cellular proliferation in draining lymph nodes is measured by determining the... 

The induction of an immune response by various mucosal routes is an important approach for the control of mucosally acquired infections. The apparent linked nature of the mucosal immune system enables the delivery of an antigen to any mucosal surface to have the secondary effect of potentially inducing immunity at others. Induction of a combination of systemic and secretory immune responses can be determined by the nature of the antigen, the route of administration, and the delivery system utilized. For example, traditional parenteral vaccines primarily induce IgM and IgG responses, whereas mucosal vaccination can elicit both IgG and secretory IgA responses (Corthesy, 2007). 

This results in expression of the antigen and the subsequent induction of an immune response to the expressed proteinAs the protein antigen is produced naturally in vivo, both cellular and humoral responses are developed. Skin has been proposed as an attractive site of immunization, and several skin cell types can become involved in DNA uptake, antigen expression and presentation. Quite recently, for example, in a mouse model, immunization has been reported following topical application of an aqueous solution of naked Given what one knows... 

The major problem of recombinant HSV-1 vectors is their cytopathic effect and the induction of an immune response by viral gene expression. The development of amplicon vectors and a helper vims-free packaging system has overcome this problem to a great extent (123-125). However, additional deletion of nonessential genes from the bac packaging system may be necessary to further prevent the cytotoxicity of this vector system. 

Another severe problem can be caused by the induction of an immune response (or pre-existing immune response) against constituents of the vector. This was the reason for the death of Jesse Gelsinger in 1999 [12]. 

Injection of Naked Nucleic Acids. Although in vitro cultured cells do not usually take up naked nucleic acids (pDNA or mRNA) spontaneously, skin cells and muscle cells do in vivo. As published in the milestone article by Wolff et al. [18] and presented in Figure 7.2-4, the direct injection of pDNA or mRNA resuspended in an isotonic buffer results in the local uptake of the nucleic acid that can be visualized by the expression of the encoded protein (luciferase, EGFP, CAT, or P-galactosidase are easily detectable markers) or by the induction of an immune response directed against the encoded protein. This is true whether the injection is made intramuscular, intradermal, or subcutaneous (review by Wolff and Budker... 

Although it must be considered just a theory at present, the danger model has significantly changed our perspective on what is involved in the induction of an immune response, and it has obvious implications for idiosyncratic drug reactions, most of which are likely immune-mediated. 

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