scholarly journals Natural Bactericidal Antibodies: Observations on the Bactericidal Mechanism of Normal Serum

1931 ◽  
Vol 31 (1) ◽  
pp. 35-55 ◽  
Author(s):  
T. J. Mackie ◽  
M. H. Finkelstein

1. An analytical study has been made of the mechanism of natural bactericidal action by the serum of various animals (ox, sheep, horse, rabbit, guinea-pig, rat, man) towards certain organisms (B. typhosus, B. dysenteriae Shiga, B. proteus, V. cholerae) exhibiting the maximum reactivity to this effect.2. Serum-complement has no bactericidal action per se, and an antibodylike agent invariably acts as an intermediary agent, “sensitising” the particular organism to the action of the complement and capable of being “absorbed” by it from serum at 0° C.3. This sensitising agent is stable at 55° C. but labile at 60°–65° C. In this respect it resembles natural haemolysins and agglutinins, but contrasts with the more stable immune antibodies and the more labile natural complement-fixing antibodies (for bacterial antigens). It is resident mainly in the carbonic-acid-insoluble fraction of the serum. It is present in the serum of young animals before certain other natural antibodies have developed.4. Absorption tests demonstrate the high degree of specificity of these natural bactericidal antibodies for particular bacteria.5. A non-specific extracellular substance occurs in bacterial cultures which may neutralise or inhibit these antibodies, and interfere with their sensitising action even at 0° C.6. This substance is liberated in large amount in cultures heated at high temperatures (120° C). It can be removed by repeated washing of growths in saline solution. It may inactivate a bactericidal antibody in heated serum, though not in fresh unheated serum, and may inactivate a particular antibody in the serum of one animal species but not in another. Strains of bacteria vary in their production of this substance.7. The observations submitted in this paper, correlated with previous studies of natural antibodies by the authors and others, indicate that immune antibodies have their precursors specifically differentiated in the serum of normal animals and that, in general, immune antibodies are not substances formed de novo.

1930 ◽  
Vol 30 (3) ◽  
pp. 337-356 ◽  
Author(s):  
H. J. Gibson

1. A study has been made of natural agglutination as exemplified by the reactions of the serum of nine animal species with a variety of bacteria.2. End-titres are recorded, and the fact is noted that sera of different animal species show an order of agglutinating activity which is almost constant for all organisms used. Ox, pig and horse sera give consistently strong reactions, while specimens from rabbit, guinea-pig and rat react weakly or not at all. Sheep, human and cat sera occupy an intermediate position. Variations are noted, however, with different individual specimens of serum from the same species.3. Organisms of the series tested can also be grouped in order according to their apparent susceptibility to agglutination by normal sera.4. The serum of young animals is found to be deficient in the agglutinating principle.5. The agglutinating effect shows a thermolability intermediate between that of complement and the immune agglutinins. Complete inactivation occurs as a rule after exposure to 60° C.–65° C. for half-an-hour. For certain strains the serum principle is inactivated at much lower temperatures.6. Lability curves show marked irregularity. In certain cases a zone of relative inactivation is produced at a temperature of 55° C.7. The natural agglutinating substance is found to be present in greater degree in the carbonic acid insoluble fraction of serum than in the carbonic acid soluble fraction. In this respect it differs from the immune agglutinins, which are chiefly located in the carbonic acid soluble moiety.8. The agglutinating principle for each organism can be absorbed completely by the homologous strain, when a variable lowering of the end-titre for other unrelated organisms results. A similar lowering of activity for these organisms may be produced by treating the serum with non-specific physical absorbents. Charcoal and Kieselguhr were used to demonstrate this.9. By the technique of double absorption it can be shown that agglutination depends on non-specific and specific factors and it is concluded that normal serum agglutinates bacteria in virtue of a twofold mechanism:(a) A non-specific effect reacting in varying degree with all organisms and removable by treatment with a finely divided absorbent.(b) A series of specific effects reacting as true “natural antibodies.” These specific antibody-like principles exist for a wide variety of organisms. Absorption of any one organism removes the homologous effect leaving the remainder quantitatively unimpaired.10. The question of bacterial variation and receptor analysis in relation to the natural agglutinins is being studied and will be reported on at a later date.


1932 ◽  
Vol 55 (2) ◽  
pp. 235-246 ◽  
Author(s):  
Joyce Wright ◽  
Hugh K. Ward

1. By a suitable bactericidal technique, it can be demonstrated that the virulent S influenza bacillus is completely resistant to the bactericidal action of diluted normal unheated serum. In contrast, the R organism is easily killed when subjected to the action of diluted normal serum. Although this is not a true virulence test, it promises to be a useful substitute when a susceptible animal is not available. 2. The S culture filtrate contains a substance with a strong antibactericidal effect, but the R culture filtrate does not contain this substance. 3. It would appear probable that this antibactericidal substance is identical with, or closely related to the precipitinogen (or soluble substance) which is present only in the culture fluid of the S influenza bacillus. In view, however, of differences in heat stability of the two substances, this question must remain in doubt until a supply of purified precipitinogen is available. 4. Quantitative agglutination, precipitation and bactericidal comparisons between (a) R-absorbed anti-S serum and unabsorbed anti-S serum and (b) anti-S serum and anti-R serum indicate that the agglutinogen is a separate antigen, and the agglutinin a separate antibody, taking no part in the bactericidal action of the antiserum. They also indicate that the precipitin, which is present only in the anti-S serum, is identical with the bactericidal antibody. 5. The relation of the precipitinogen (or soluble substance) to virulence and of the precipitin to resistance is discussed.


2018 ◽  
Vol 16 (05) ◽  
pp. 362-368 ◽  
Author(s):  
Federica Sullo ◽  
Agata Polizzi ◽  
Stefano Catanzaro ◽  
Selene Mantegna ◽  
Francesco Lacarrubba ◽  
...  

Cerebellotrigeminal dermal (CTD) dysplasia is a rare neurocutaneous disorder characterized by a triad of symptoms: bilateral parieto-occipital alopecia, facial anesthesia in the trigeminal area, and rhombencephalosynapsis (RES), confirmed by cranial magnetic resonance imaging. CTD dysplasia is also known as Gómez-López-Hernández syndrome. So far, only 35 cases have been described with varying symptomatology. The etiology remains unknown. Either spontaneous dominant mutations or de novo chromosomal rearrangements have been proposed as possible explanations. In addition to its clinical triad of RES, parietal alopecia, and trigeminal anesthesia, CTD dysplasia is associated with a wide range of phenotypic and neurodevelopmental abnormalities.Treatment is symptomatic and includes physical rehabilitation, special education, dental care, and ocular protection against self-induced corneal trauma that causes ulcers and, later, corneal opacification. The prognosis is correlated to the mental development, motor handicap, corneal–facial anesthesia, and visual problems. Follow-up on a large number of patients with CTD dysplasia has never been reported and experience is limited to few cases to date. High degree of suspicion in a child presenting with characteristic alopecia and RES has a great importance in diagnosis of this syndrome.


2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Shujun Ou ◽  
Weija Su ◽  
Yi Liao ◽  
Kapeel Chougule ◽  
Jireh R. A. Agda ◽  
...  

Abstract Background Sequencing technology and assembly algorithms have matured to the point that high-quality de novo assembly is possible for large, repetitive genomes. Current assemblies traverse transposable elements (TEs) and provide an opportunity for comprehensive annotation of TEs. Numerous methods exist for annotation of each class of TEs, but their relative performances have not been systematically compared. Moreover, a comprehensive pipeline is needed to produce a non-redundant library of TEs for species lacking this resource to generate whole-genome TE annotations. Results We benchmark existing programs based on a carefully curated library of rice TEs. We evaluate the performance of methods annotating long terminal repeat (LTR) retrotransposons, terminal inverted repeat (TIR) transposons, short TIR transposons known as miniature inverted transposable elements (MITEs), and Helitrons. Performance metrics include sensitivity, specificity, accuracy, precision, FDR, and F1. Using the most robust programs, we create a comprehensive pipeline called Extensive de-novo TE Annotator (EDTA) that produces a filtered non-redundant TE library for annotation of structurally intact and fragmented elements. EDTA also deconvolutes nested TE insertions frequently found in highly repetitive genomic regions. Using other model species with curated TE libraries (maize and Drosophila), EDTA is shown to be robust across both plant and animal species. Conclusions The benchmarking results and pipeline developed here will greatly facilitate TE annotation in eukaryotic genomes. These annotations will promote a much more in-depth understanding of the diversity and evolution of TEs at both intra- and inter-species levels. EDTA is open-source and freely available: https://github.com/oushujun/EDTA.


1962 ◽  
Vol 115 (1) ◽  
pp. 131-146 ◽  
Author(s):  
J. Gabriel Michael ◽  
James L. Whitby ◽  
Maurice Landy

A study was made of the origin, occurrence, and properties of natural antibodies to Gram-negative bacteria in the normal serum of several species. Antibody was measured by a procedure based on the bactericidal reaction carried out under conditions in which activity was a function of the amount of antibody contributed by the test serum. Antibody to seven genera of the family Enterobacteriaceae were demonstrated in normal human serum. The specificity of these antibodies was affirmed by absorption with homologous bacteria and by inhibition of bactericidal activity with purified homologous somatic antigen. Absorption with graded amounts of bacterial suspensions showed that a large excess of bacteria led to non-specific removal of antibodies. Analogous findings were also made with immune antibody. As determined by quantitative absorption tests no difference could be found in the avidity of natural and immune antibody. Natural antibody in the serum of various species differed considerably as regards their lability to heat, but in parallel tests immune antibody of each species was significantly more heat-stable. The time and appearance of the antibodies varied in young animals, of different species. Mice developed these antibodies at the earliest age, with guinea pigs, rats, and rabbits following in that order. Serum from germ-free rats and chickens had no demonstrable antibodies to E. coli or S. typhosa whereas these antibodies were present in the serum of litter mates reared under conventional conditions. On the other hand germ-free and conventional mice did not differ appreciably as regards the levels of these same antibodies.


1964 ◽  
Vol 12 (9) ◽  
pp. 647-653 ◽  
Author(s):  
HOWARD H. CHAUNCEY ◽  
JOSEPH H. KRONMAN ◽  
MAYER A. LEVITT

Acid phosphatase, alkaline phosphatase, nonspecific esterase, pseudocholinesterase, leucine aminopeptidase, and β-d-galactosidase activities of parotid and submandibular salivary glands were evaluated in six animal species. Assays for total enzyme, lyoenzyme, and demoenzyme were performed on unfixed and chloral hydrate formalin (CHF) fixed frozen cryostat sections. Following fixation lyoenzyme (soluble fraction) activity exhibited extreme reduction for all enzymes except pseudocholinesterase, while the demoenzyme (insoluble fraction) activity of acid phosphatase, nonspecific esterase, pseudocholinesterase, and β-d-galactosidase was maintained at a high level or increased. Since removal of lyoenzyme activity and retention of desmoenzyme activity are requisites in histochemical localization, this fixative may be the preferred method for handling tissues prior to the localization of the above cited enzymes. Several hypotheses are proposed to explain the increased desmoenzyme (nonspecific esterase and β-d-galactosidase) noted subsequent to fixation.


1964 ◽  
Vol 119 (1) ◽  
pp. 53-70 ◽  
Author(s):  
David W. Weiss ◽  
Rose S. Bonhag ◽  
James A. Parks

Small quantities of the non-toxic residue of phenol-killed, acetone-washed, and methanol-extracted tubercle bacilli of the BCG strain conferred a high degree of resistance on mice against otherwise lethal experimental infection with Klebsiella pneumoniae and with a number of other pathogenic bacteria. The heightened resistance reached a peak within 24 hours after administration of the fraction, but was already discernible immediately thereafter. A period of reduced resistance was not observed. The state of heightened resistance was invariably manifested for at least 10 days, and could frequently still be demonstrated after several weeks or months. The methanol-insoluble fraction was immunogenically active even in experimental circumstances under which living BCG exerted no effect. Its protective effect was more marked in females than in males. The optimum dosage must be determined empirically vis-á-vis the strain of infecting organisms and the experimental parameters of administration and testing. Administration of the fraction to breeding females reduced the incidence of a naturally occurring endemic pneumonitis among their young, and increased considerably the breeding productivity of the mothers. These effects were manifested as late as 11 months after treatment.


1968 ◽  
Vol 14 (1) ◽  
pp. 53-60 ◽  
Author(s):  
C. Margaret Johnson ◽  
John C. N. Westwood

Precipitins against influenza A/PR8 were detected in the serum of normal rabbits with a highly sensitive cellulose acetate micro-immunodiffusion technique which allows the diffusion of whole virus particles. Rabbits were susceptible to subclinical artificially induced influenza A/PR8 infection. These natural antibodies might be indicative of natural infection in animal populations with influenza A/PR8 or a closely related influenza A strain. Similar immunodiffusion reactions were observed with normal serum from a sheep, a goat, guinea pigs, and roosters.


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