Immunization with ribosomes

We have seen in various sections of this article that anti-RNA antibodies induced by immunization with ribosomes and the antibodies to pol3uibo-nucleotide complexes — MBSA have made possible a more direct approach to the study of the conformation and structure of synthetic polynucleotides and both viral and non-viral natural ribonucleic acids. 

Immune sera against poly A poly U, anti-poly I poly C and anti-poly G were used as controls. Anti-poly G does not precipitate any of the RNAs tested, whereas antibodies to the two complementary complexes precipitate all the RNAs, regardless of origin or fraction (Table 7 to 9). Thus antipoly G poly C antibodies show a specificity for ribosomal RNA from animal cells, and for certain viral RNAs furthermore they distinguish between rRNA and tRNA. In contrast, antibodies obtained by immunization with other polynucleotide complexes such as poly A poly U and poly I poly C show no specificity for any RNA whatever its type or origin, with the exception however of double-stranded viral RNA (Stollar, 1970). 

Fig. 8. Mapping of proteins on the E. colt 30 S ribosomal subunit by immune electron microscopy, (a) StbfBer-Meilicke and StOffler (1983) (b) Winkelmann et al. (1982). Reproduced with permission from Wittmann (1983).

Linezohd (Zyvox) is an oxazolidinone, a tive-membered heterocychc ring that forms the core of the hnezohd structure. The approval of hnezohd by the FDA in 2000 marked the first new structural class of antibacterial introduced into medical practice in the United States in 40 years. It is notable for its activity against methicillin-resistant Staph aureus, MRSA, and vancomycin-resistant Enterococcus faecium, VRE. It is bacteriostatic rather than bactericidal but finds significant use in patients with an intact immune system. Like several other classes of antibacterials, linezolid is an inhibitor of protein synthesis. It interacts specifically with the RNA component of a bacterial ribosome subunit to prevent initiation of protein synthesis. 

As previously indicated, the primary cells involved in the immune response are lymphocytes which have a centrally located round nucleus, lack specific granules, and have a basophilic cytoplasm containing free ribosomes. The (thymus-dependent) T-lyniphocytes are involved in cell mediated reactions and also interact with B-Iymphocytes (see later) to regulate the production of antibody, The B cells differentiate into the antibody-producing plasma cells. There is growing evidence that neither T... 

In ribosome display, the physical link between genotype and phenotype is accomplished by mRNA-ribosome—protein complexes, which are directly used for selection. If a library of different mRNA molecules is translated, a protein library results in which each protein is produced from its own mRNA and remains connected to it. Since these complexes of the proteins and their encoding mRNAs are stable for several days under the appropriate conditions, very stringent selections can be performed. As all steps of ribosome display are carried out in vitro, reaction conditions of the individual steps can be tailored to the requirements of the protein species investigated, as well as the objectives of the selection or evolution experiment. Application of ribosome display has produced scFv fragments of antibodies with affinities in the picomolar range from libraries prepared from immunized mice (Hanes et al., 1998) and more recently from a naive, completely synthetic library (Hanes et al., 2000), and has been used to evolve improved off-rates and stability (Jermutus et al., 2000). 

Profeins often exert their function through interaction with other ones, forming complexes, e.g., in fhe ribosome or in cell membranes, during immune response or enzyme cafalysis. Complex... 

More than 30 million people, infected by the human immunodeficiency virus (HIV), suffer from the acquired immune deficiency syndrome (AIDS) 2 billion humans carry the hepatitis B vims (HBV) within themselves, and in more than 350 million cases the liver disease caused by the HBV is chronic and, therefore, currently incurable. These are only two examples of worldwide epidemics due to vims infections. Vimses typically consist of a compactly folded nucleic acid (single- or double-stranded RNA or DNA) encapsulated by a protein hull, Proteins in the hull are responsible for the fusion of the vims with a host cell. Vims replication, by DNA and RNA polymerase in the cell nucleus and protein synthesis in the ribosome, is only possible in a host cell. Since regular cell processes are disturbed by the vims infection, serious damages or even the destmction of the fine-tuned functional network within a biological organism can be the consequence. 

In contrast with the immune sera against poly A poly U and poly I poly C, no reaction between anti-poly G poly C and RNA from S err alia marcescens, Streptococcus faecalis and Escherichia coli occurred (Table 8) whether ribosomal RNA, tRNA or formaldehyde-treated RNA was used (Nahon-Merlin et al., 1971). 

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