scholarly journals The effects of humoral, cellular and non-specific immunity on intracerebralBordetella pertussisinfections in mice

1975 ◽  
Vol 74 (1) ◽  
pp. 85-102 ◽  
Author(s):  
Jean M. Dolby ◽  
D. E. Dolby ◽  
Caroline J. Bronne-Shanbury

When mice were injected intracerebrally with doses ofBordetella pertussisvaccine greater than 5 ImD50 and challenged intracerebrally 14 days later with virulentB. pertussisthere was an immediate reduction in the numbers of organisms. An analysis of thisin vivobactericidal effect has shown that large doses of an unrelated vaccine,Salmonella typhosa, equivalent in cell mass to about 50 ImD 50 ofB. pertussisvaccine can achieve this effect, so for such doses the effect must be partly non-specific. This action is not maintained and so is not ultimately protective. Local immunoglobulin was also demonstrable 14 days after 300 ImD 50 ofB. pertussisvaccine but following smaller doses of 10–20 ImD 50 it could not be found until after the mice had been infected and the blood–brain barrier impaired.A similar immediate reduction in the numbers of infecting organisms inoculated 1 day after vaccination has been shown to follow very small, non-protective doses of vaccines unrelated toB. pertussisand to be achieved with lipopolysaccharide and endotoxin isolated fromB. pertussis.Brains were not sterilized and only in mice receiving protectiveB. pertussisvaccine was the lowering of infection maintained beyond 2 days and the brains eventually sterilized.The antibody passively protecting mice against intracerebral infection was found in the 19 S and 11 S globulin fractions of the serum of once-vaccinated mice and in the 11 S and 7 S fractions of the serum of rabbits and ascitic fluid of mice receiving repeated doses of vaccine. The IgM probably eliminated infections by immediate sterilization but had to be present locally to do so since it was unable to pass from the circulation into the brain, and was therefore inactive when injected intraperitoneally. The IgA and IgG were not so restricted and both the 11 S and 7 S globulins were capable of exerting an immediate suppressive effect on infecting organisms. The 7 S globulin was also capable of a maintained or delayed suppressive effect.Lymphocytes from fully protected once-vaccinated mice, transferred 2–3 weeks after intraperitoneal vaccination, were able to confer some protection when injected intraperitoneally or intracerebrally into recipient mice infected 2 weeks after transfer. Homologous, non-concentrated antiserum from once-vaccinated mice, injected intraperitoneally 1 hr. before infection sometimes augmented the transferred immunity, whereas alone it was inactive.

1972 ◽  
Vol 70 (4) ◽  
pp. 707-718 ◽  
Author(s):  
Jean M. Dolby

SUMMARYThe passive protection of mice against an intracerebral infection with Bordetella pertussis, by antiserum introduced directly into the brain with the infecting organisms, was compared with the protection afforded by intraperitoneal antiserum. The antibody effective by the intracerebral route is that which is adsorbed onto the infecting organisms, although it does not affect the viability of the organisms in vitro in the absence of complement.Passive protection against organisms introduced intracerebrally takes place in one of two ways, depending on the size of the challenge: (1) after 3–4 days' growth, the growth rate declines so that the number of organisms does not reach the figure lethal for the mouse; (2) the organisms do not appear to multiply, as their numbers decline from the moment of injection, so that the brain is sterile after 2 days.Many of the mice protected against a challenge of 50,000 organisms (ca. 100 LD50) by intraperitoneal or intracerebral antiserum recover by the first mechanism. The second mechanism operates after a smaller challenge of 5000 organisms (ca. 10 LD50), irrespective of whether the antiserum is given intracerebrally with the challenge, or intraperitoneally within several hours of challenge. Too much antiserum given intracerebrally with a 50,000 challenge, but not with a 5000 challenge, inhibits protection.In some mice, virulent antibody-treated organisms which have not been killed, grow very slowly over a long period, but are eventually eliminated from the brain.


1961 ◽  
Vol 59 (2) ◽  
pp. 205-216 ◽  
Author(s):  
Jean M. Dolby ◽  
A. F. B. Standfast

The growth of virulent strains of Bordetella pertussis in the brains of mice was studied by carrying out viable counts on mice killed at various times during the infection. The results suggested that this system conformed to the general model which postulates that the organisms causing death multiply in vivo at a rate which is constant for all doses and that death is certain to occur when the number of organisms reaches a certain constant figure.Perhaps the most important factor in this route of infection is the lodgement of the parasite in the host, for if this is accomplished a single organism grows until the lethal level is reached. There is no sublethal infection.In actively and passively protected mice, the growth of the organism is approximately the same as in unprotected controls for the first 4–5 days. At this time there is a striking change in protected animals and the viable count falls rapidly and progressively and the animals survive. At the same time the blood-brain barrier becomes permeable and circulating antibodies diffuse into the brain. In vitro, specific antisera plus complement are highly bactericidal.


1972 ◽  
Vol 70 (3) ◽  
pp. 487-501 ◽  
Author(s):  
A. F. B. Standfast ◽  
Jean M. Dolby

SUMMARYThe development of immunity in mice to Bordetella pertussis induced by intracerebral, intravenous or intraperitoneal vaccination was analysed in terms of the viable bacteria in the brain after intracerebral challenge, the serum antibodies, and protection against the sublethal infection of the lung that follows intranasal inoculation.A vaccine introduced intracerebrally was five to ten times more effective than that given intraperitoneally or intravenously, as measured for each route by the amount of vaccine required to protect half the mice against an intracerebral challenge 14 days later (ImD50). Intracorebral vaccination induced higher antibody titres than vaccination by the other two routes. The survival of infected mice given 1–3 ImD50 doses of vaccine intracerebrally 14 days before, followed a pattern similar to that after intraperitoneal or intravenous vaccination with up to 10 ImD50 of vaccine: the numbers of organisms increased for 3 days and then declined. Injection of about four ImD50 of vaccine intracerebrally produced a local immunity, resulting in an immediate kill of challenge organisms given 14 days later. Such an effect following intraperitoneal vaccination was achieved only against challenges with an avirulent strain. It is suggested that better stimulation of circulating antibody and local immunity in the brain together account for the better protection induced by intracerebral vaccine.Immunity to an intracerebral infection appears therefore to have at least three components, each specific for pertussis. The first, like that induced by intraperitoneal and intravenous vaccination, reaches a maximum in 2 or 3 weeks and is probably an expression of a general response by the animal operating not earlier than 3 days after infection. The second is a local immunity, appearing after the same interval. The third is a short-lived local immunity which has been described by previous workers; it immediately follows the injection intracorebrally of ten times less vaccine than that needed to protect against a challenge 14 days later and lasts only 2–3 days. The second and third types result in immediate sterilization of the infection.Mice recovering from sublethal brain infection with avirulent organisms were immune to a second infection with a virulent organism, but this was achieved not by the ability to kill the re-infecting organisms immediately on injection into the brain, but only after the 3–4 days lag such as follows intraperitoneal vaccination.


2017 ◽  
Author(s):  
Jiaming Cao ◽  
Pulkit Grover

AbstractUsing a systematic computational and modeling framework, we provide a novel Spatio-Temporal Interference-based stiMULation focUsing Strategy (STIMULUS) for high spatial precision noninvasive neurostimulation deep inside the brain. To do so, we first replicate the results of the recently proposed temporal interference (TI) stimulation (which was only tested in-vivo) in a computational model based on a Hodgkin-Huxley model for neurons and a model of current dispersion in the head. Using this computational model, we obtain a nontrivial extension of the 2-electrode-pair TI proposed originally to multielectrode TI (> 2 electrode pairs) that yields significantly higher spatial precision. To further improve precision, we develop STIMULUS techniques for generating spatial interference patterns in conjunction with temporal interference, and demonstrate strict and significant improvements over multielectrode TI. Finally, we utilize the adaptivity that is inherent in STIMULUS to create multisite neurostimulation patterns that can be dynamically steered over time.


1961 ◽  
Vol 59 (2) ◽  
pp. 217-229 ◽  
Author(s):  
A. F. B. Standfast ◽  
Jean M. Dolby

1. The main differences between intracerebral and intranasal infections in mice with virulent strains of Bordetella pertussis are in: (1) the responses to small in fecting doses (< 1 LD 50); (2) the action of antisera in controlling infection; (3) the action of toxin on brain and lung; and (4) the rates of increase of the viable count. The two infections can run concurrently in the same mouse without any demonstrable interference.2. The terminal viable count in the lung and brain is c. 108 organisms.3. In the brain there is no sublethal infection with virulent strains; probably even single organisms can grow up to the critical level and kill the mouse. In the lung sublethal infections are found in which the count rises to a figure below the critical level and then declines.4. The action of ‘intranasal’ antiserum is to reduce a lethal infection to a sublethal one in the lung but there is no effect in the brain. ‘Intracerebral’ antisera cannot act until the blood-brain barrier becomes leaky, when they are able to reduce the viable count and eventually sterilize the brain. In the lung ‘intracerebral’ sera have no action against lethal infections but can control small infections (<I LD 50). The sublethal intranasal test measures this effect but it also measures the action of ‘intranasal’ sera and so cannot be used to distinguish the two types of sera and hence the two antigens.


1943 ◽  
Vol 78 (3) ◽  
pp. 161-168 ◽  
Author(s):  
René J. Dubos ◽  
June Hookey Straus ◽  
Cynthia Pierce

1. Anti-Shiga bacteriophage injected into the general circulation can multiply in the brain of mice infected intracerebrally with Shigella dysenteriae. 2. Under proper conditions, the injection of active bacteriophage into the general circulation can protect mice against an otherwise fatal intracerebral infection with Shigella dysenteriae. 3. The protection so induced appears to depend upon the early establishment of a high bacteriophage level in the infected animal.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daniel E. Troyetsky ◽  
Jeffrey Tithof ◽  
John H. Thomas ◽  
Douglas H. Kelley

AbstractAccumulation of metabolic wastes in the brain is correlated with several neurodegenerative disorders, including Alzheimer’s disease. Waste transport and clearance occur via dispersion, the combined effect of diffusion and advection by flow of fluid. We examine the relative contributions of diffusion and advection in the perivascular spaces (PVSs) that surround penetrating cortical blood vessels and are filled with cerebrospinal fluid (CSF). To do so, we adapt prior analytic predictions of dispersion to the context of PVSs. We also perform advection-diffusion simulations in PVS-like geometries with parameters relevant to transport of amyloid-$$\beta$$ β (associated with Alzheimer’s) in a variety of flows, motivated by in vivo measurements. Specifically, we examine solute transport in steady and unsteady Poiseuille flows in an open (not porous) concentric circular annulus. We find that a purely oscillatory flow enhances dispersion only weakly and does not produce significant transport, whereas a steady flow component, even if slow, clears waste more effectively.


2001 ◽  
Vol 21 (22) ◽  
pp. 7787-7795 ◽  
Author(s):  
Joong K. Kim ◽  
Sung-Oh Huh ◽  
Heonsik Choi ◽  
Kee-Sook Lee ◽  
Dongho Shin ◽  
...  

ABSTRACT Srg3 (SWI3-related gene product) is a mouse homolog of yeast SWI3,Drosophila melanogaster MOIRA (also named MOR/BAP155), and human BAF155 and is known as a core subunit of SWI/SNF complex. This complex is involved in the chromatin remodeling required for the regulation of transcriptional processes associated with development, cellular differentiation, and proliferation. We generated mice with a null mutation in theSrg3 locus to examine its function in vivo. Homozygous mutants develop in the early implantation stage but undergo rapid degeneration thereafter. An in vitro outgrowth study revealed that mutant blastocysts hatch, adhere, and form a layer of trophoblast giant cells, but the inner cell mass degenerates after prolonged culture. Interestingly, about 20% of heterozygous mutant embryos display defects in brain development with abnormal organization of the brain, a condition known as exencephaly. Histological examination suggests that exencephaly is caused by the failure in neural fold elevation, resulting in severe brain malformation. Our findings demonstrate that Srg3 is essential for early embryogenesis and plays an important role in the brain development of mice.


Author(s):  
Beverly E. Maleeff ◽  
Timothy K. Hart ◽  
Stephen J. Wood ◽  
Ronald Wetzel

Alzheimer's disease is characterized post-mortem in part by abnormal extracellular neuritic plaques found in brain tissue. There appears to be a correlation between the severity of Alzheimer's dementia in vivo and the number of plaques found in particular areas of the brain. These plaques are known to be the deposition sites of fibrils of the protein β-amyloid. It is thought that if the assembly of these plaques could be inhibited, the severity of the disease would be decreased. The peptide fragment Aβ, a precursor of the p-amyloid protein, has a 40 amino acid sequence, and has been shown to be toxic to neuronal cells in culture after an aging process of several days. This toxicity corresponds to the kinetics of in vitro amyloid fibril formation. In this study, we report the biochemical and ultrastructural effects of pH and the inhibitory agent hexadecyl-N-methylpiperidinium (HMP) bromide, one of a class of ionic micellar detergents known to be capable of solubilizing hydrophobic peptides, on the in vitro assembly of the peptide fragment Aβ.


Author(s):  
Enrico D.F. Motti ◽  
Hans-Georg Imhof ◽  
Gazi M. Yasargil

Physiologists have devoted most attention in the cerebrovascular tree to the arterial side of the circulation which has been subdivided in three levels: 1) major brain arteries which keep microcirculation constant despite changes in perfusion pressure; 2) pial arteries supposed to be effectors regulating microcirculation; 3) intracerebral arteries supposed to be deprived of active cerebral blood flow regulating devices.The morphological search for microvascular effectors in the cerebrovascular bed has been elusive. The opaque substance of the brain confines in vivo investigation to the superficial pial arteries. Most morphologists had to limit their observation to the random occurrence of a favorable site in the practically two-dimensional thickness of diaphanized histological sections. It is then not surprising most investigators of the cerebral microcirculation refer to an homogeneous network of microvessels interposed between arterioles and venules.We have taken advantage of the excellent depth of focus afforded by the scanning electron microscope (SEM) to investigate corrosion casts obtained injecting a range of experimental animals with a modified Batson's acrylic mixture.


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