Cell-free immunity

BOMAN HG, HULTMARK D. Cell-free immunity in insects. Annu Rev Microbiol 1987 41 103-26. 

UV-irradiated cells. Using cell-free cytosolic keratinocyte extracts, Simon and colleagues26 confirmed the role of membrane oxidation in NF-kB activation. Particularly important aspects of the experimental design employed by Simon and colleagues was the use of keratinocytes versus cells derived from a cervical cancer patient, and the use of biologically relevant UVB (290 to 320 nm) radiation versus UVC (200 to 290 nm) radiation, which is filtered out by the atmospheric ozone layer and does not reach the earth s surface. Overall, these data indicate that the activation of cytokine transcription, a step essential for the induction of immune suppression, can occur independently of UV-induced DNA damage and suggest that membrane lipid oxidation can serve as a UV photoreceptor. 

Antigen delivery through liposomes, hollow membrane-bound spheres, can be achieved by entrapping the molecule in the lipid membrane or inside the hollow cavity. Modified liposomes have been able to induce mucosal IgA responses compared to free antigen (Ann Clark et al. 2001 Aziz et al. 2007). Liposomes containing pertussis toxin (Guzman et al. 1993), Streptococcus mutans (Childers et al. 2002), or bovine serum albumin (Therien et al. 1990) as vaccine antigens have been tested in experimental models and induced effective antibody- and cell-mediated immune responses. 

While most polysaccharide antigens act in a T-cell independent fashion, zwitterionic polysaccharides have been shown to induce T-cell mediated immunity [358]. Several bacteria produce zwitterionic CPS, which contain both free amine and free carboxyl groups in the repeating unit. These include CPS types 5 and 8 of Staphylococcus aureus, PSA from B. frag-ilis and the type 1 S. pneumoniae polysaccharide (O Fig. 28). Vaccination with zwitterionic polysaccharides have been shown to produce T-cell mediated immunity in mice [359], and vaccines based on zwitterionic CPS may be useful for combating several common bacterial pathogens. 

A variety of mammalian cellular systems have been used as experimental models for documenting the in vitro effects of cannabinoids on immune responsiveness to viruses, bacteria, and amoebae. Blevins and Dumic (1980) indicated that THC had a protective effect against HSV infection in vitro. It was found that both HSV-1 and HSV-2 failed to replicate and produce extensive cytopathic effect (c.p.e.) in human cell monolayer cultures exposed before infection, at infection, or post infection to various concentrations of THC. In contrast, other studies indicate that THC compromises resistance to virus infection. It has been reported that THC inhibits macrophage extrinsic anti-viral activity (Cabral and Vasquez 1991 Cabral and Vdsquez 1992) whereby macrophages normally suppress virus replication in cells to which they attach (Morahan et al. 1980 Stohlman et al. 1982). Noe et al. (1998) reported that a variety of cannabinoid receptor agonists enhanced syncytia formation in human T cell leukemia virus-I (HTLV-I)-transformed human T (MT-2) cells infected with cell free human immunodeficiency virus (HIV-IMN). It was found that CP 55,940, THC, WIN 55,212-2, and WIN 55,212-3 significantly increased syncytia formation, a phenomenon that has been reported to serve as an indicator of HIV infection and cytopathicity. 

Although interferons are mediators of immune response, different mechanisms for the antiviral action of interferon have been proposed. Interferon-a possesses broad-spectrum antiviral activity and acts on virus-infected cells by binding to specific cell surface receptors. It inhibits the transcription and translation of mRNA into viral nuoleic acid and protein. Studies in cell-free systems have shown that the addition of adenosine triphosphate and double-stranded RNA to extracts of interferon-treated cells activates cellular RNA proteins and a oellular endonuclease. This activation causes the formation of translation inhibitory protein, which terminates production of viral enzyme, nucleic acid, and structural proteins (28). Interferon also may act by blocking synthesis of a cleaving enzyme required for viral release. 

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