Immune system, evasion

Mucins, Immune System Evasion and Cancer Development. 2666... 

Viruses use a large variety of mechanisms to evade cellular defense mechanisms. Almost every aspect of the innate or adaptive immune systems provides some opportunity for evasion.)) The rapid... 

A. Alcami and U. H. Koszinowski, Viral mechanisms of immune evasion, Trends in Microbiology, 8, 2000, 410-18 D. Tortorella et al., Viral subversion of the immune system, Annual Review of Immunology, 18, 2000, 861-926. 

As we learn more about the precise molecular features that contribute to immu-nogenicity, further improvements will be made in antibody composition to reduce this effect. However, for the foreseeable future, only clinical data in humans will allow determination of the severity of the effect and whether it has a negative impact on clinical utility. As a result of the reliance on human clinical data to determine immunogenicity, we may expect further progress in this area to be slow. It remains to be seen whether the molecular understanding of this complex process will advance to a point that immunogenicity can be engineered out at the amino acid level. It is also possible that a complete evasion of the immune system will simply not be possible in all cases. 

The role of an immune-evasive gene in vivo can only be proven for MCMV and RCMV as a model for HCMV. Even though the mode of action to evade the host immune system may be different in HCMV and MCMV with respect to mechanistic details, the use of an animal model can show the relevance of the interaction between the virus functions and the host immune system. 

The immune system has evolved so as to require only minute amounts of antigen for detection of a foreign invader. Herpesviruses have withstood the selective pressure exerted by the host through evasion of the host immune response and have had millions of years to bring these strategies to perfection. The fact that most, if not all, herpesviruses are capable of establishing persistent infections illustrates the effectiveness of the stealth technology employed by these viruses. 

Johnson DC, Hill AB (1998) Herpesvirus evasion of the immune system. Curr Top Microbiol Immunol 232 149-177... 

From what is known about CMV-encoded chemokines and chemokine receptors, it appears that their participation in immune evasion would be mainly at the level of viral dissemination sheltered from the immune system through (cell-to-cell) passage and movement of receptor bearing infected cells bidirectionally across endothelial barriers. In addition, the ability of pUS28 to withdraw CC chemokines from the environment of infected cells could also confer a measure of immune evasion by blunting effector lymphocyte migration and activation. 

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. 

Figure2. Staphylococcal innate immune evasion. The molecules produced by S-aureusthatcounteract the different steps of our innate immune system. SSL-5 (Staphylococcal Superantigen-like 5), Eap (Extracellular adherence protein), CHIPS (Chemotaxis inhibitory protein of Staphylococci), FLIPr (FPRL-1 inhibitory protein), SSL-7 (Staphylococcal Superantigen-like 7), Efb (Extracellular fibrinogen binding protein), Ecb(Extracellularcomplementbindingprotein), protA(protein A), SCI Nl (Staphylococcal Complement inhibitor), SCIN B (Staphylococcal Complementinhibitor-B), SCIN C (Staphylococcal Complement inhibitor-C), SAK (Staphylokinase).

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