Immune response cellular barriers

Maggini, S., Wintergerst, E. S., Beveridge, S., and Hornig, D. H. (2007). Selected vitamins and trace elements support immune function by strengthening epithelial barriers and cellular and humoral immune responses. Br. ]. Nutr. 98(Suppl 1), S29-S35. 

Yang, Y., Li, Q., Ertl, H.C. and Wilson, J.M. (1995) Cellular and humoral immune responses to viral antigens create barriers to lung-directed gene therapy with recombinant adenoviruses. J. Virol., 69, 2004-2015. 

Extracellular barriers in systemic delivery involve hurdles to nucleic acid delivery encountered from the point of injection to the surface of the cellular target. For cationic polymer-based systems, these barriers typically include the toxicity of the nanoparticles, interactions with semm proteins, extracellular matrices, and nonspecific cell surfaces, clearance by the innate immune system, aggregation due to physiological salt conditions, and evasion of the adaptive immune response. Ideally, the nanoparticle should (1) remain nontoxic, small, and dis-aete, (2) bypass the immune system, and (3) interact only with the cells of interest. Efforts to prepare polymer systems that endow nanoparticles with these characteristics are discussed below. 

The hagfish, which is the most primitive vertebrate extant, is capable of mounting an immune response. Although earlier studies had suggested that the species does not exhibit cellular or humoral immunity, Hildemann and Thoenes (25) were able to demonstrate that the animal exhibits first- and second-set rejection of skin allografts, with rejection times of 72 and 28 days, respectively. The very slow rejection of the first-set graft could be due to a weak histocompatability barrier or to a poorly developed immune mechanism. The authors favor the former hypothesis on the basis of the hyperacute reaction which is observed if the second graft is applied very soon after rejection of the first. 

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