No abstract

Cerebral extracellular fluids drain from brain to blood across the arachnoid villi and to lymph along certain cranial nerves (primarily olfactory) and spinal nerve root ganglia. Quantification of the connection to lymph in rabbit, cat and sheep, using radiolabelled albumin as a marker of flow, indicates that a minimum of 14 to 47% of protein injected into different regions of brain or cerebrospinal fluid passes through lymph. The magnitude of the outflow to lymph is at variance with the general assumption that the absence of conventional lymphatics from the brain interrupts the afferent arm of the immune response to brain antigens. The immune response to antigens (albumin or myelin basic protein) introduced into the central nervous system (CNS) has been analysed using a rat model with normal brain barrier permeability. The micro-injection of antigen into brain or cerebrospinal fluid elicits a humoral immune response, with antibody production in cervical lymph nodes and spleen, and also affects cell-mediated immunity. Furthermore, antigen may be more immunogenic when administered into the CNS than into conventional extracerebral sites. Clearly, the afferent arm of the immune response to antigens, within the CNS, is intact. Modern studies suggest that the efferent arm is also intact with passage of activated lymphocytes into the brain. Results support a new view of CNS immunology which incorporates continuous and highly regulated communication between the brain and the immune system in both health and disease.

It has been well established that the ribosomal particles are the site of protein synthesis, yet we have very little insight into the mechanism.1 A great deal of attention has been directed toward the question of how the ribosomes contain the information necessary to effect the alignment of amino acids in a specific sequence. This problem has been resolved recently with the discovery of a rapidly metabolizing fraction of RNA, called messenger RNA, which has the ability to attach itself to the ribosomal particle and there to determine the sequence of amino acids.2' I This view has been considerably reinforced by in vitro experiments in which naturally occurring RNA, as well as synthetic polyribonucleotides, have been shown to provide the information necessary to determine the sequence of amino acids in a polypeptide chain.4' 5 Thus, the ribosome has a passive role in transmitting information; it can apparently polymerize a variety of proteins, depending upon the particular messenger RNA which is attached to it.However, this state of affairs has puzzled many investigators for some time. The purely geometric aspects of the messenger RNA-ribosomal interaction leave several unresolved questions. For example, the polypeptide chains in the hemoglobin molecule each contain roughly 130 amino acids and, using a triplet code, this implies a messenger of 450 nucleotides or a molecule 1,500 A long if there is one nucleotide every 3.4 A. How can this long polymer molecule transfer all of its sequence information to the ribosomal site at which the polypeptide chain is believed to grow? This becomes an even greater puzzle if one considers that much longer messenger R'NA molecules have been found.5 Indeed, the length is so great that it would almost be physically impossible for one ribosome 230 A in diameter to interact with the entire messenger chain. However, Risebrough et al.7 have shown that "heavy ribosomes" are seen in a sucrose gradient when labeled T2 messenger RNA is attached to E. coli ribosomes. More recently, several investi-gators8-10 have reported that polyuridylic acid induces the formation of a rapidly sedimenting ribosomal peak when it is added in vitro to a cell-free bacterial extract. We have therefore been prompted to look for the possible existence of a larger multiple ribosomal structure in rico which might provide insight into the detailed mechanism of protein synthesis.In these experiments, we have used reticulocyte ribosomes because it is possible to break open the reticulocyte cell wall gently with a minimum of mechanical manipulation. This approach has been successful, and we have been able to demonstrate the existence of a multiple ribosomal structure held together by RNA. In Downloaded by guest on August 1, 2020