Experimenting with Innate Immunity

libtissue is a software system for implementing and testing AIS algorithms on real-world computer security problems. AIS algorithms are implemented as a collection of cells, antigen and signals interacting within a tissue compartment. Input data to the tissue comes in the form of realtime events generated by sensors monitoring a system under surveillance, and cells are actively able to affect the monitored system through response mechanisms. libtissue is being used by researchers on a project at the University of Nottingham to explore the application of a range of immune-inspired algorithms to problems in intrusion detection. This talk describes the architecture and design of libtissue, along with the implementation of a simple algorithm and its application to a computer security problem

Experimenting with Innate Immunity

libtissue is a software system for implementing and testing AIS algorithms on real-world computer security problems. AIS algorithms are implemented as a collection of cells, antigen and signals interacting within a tissue compartment. Input data to the tissue comes in the form of realtime events generated by sensors monitoring a system under surveillance, and cells are actively able to affect the monitored system through response mechanisms. libtissue is being used by researchers on a project at the University of Nottingham to explore the application of a range of immune-inspired algorithms to problems in intrusion detection. This talk describes the architecture and design of libtissue, along with the implementation of a simple algorithm and its application to a computer security problem

Wise Blood: The Principle of Overcoming in Disease and Immunity (Part 1)

The immune system is an intelligently made system designed for interaction with microbes even in a perfect world; it is more than a defense. However, in a post-fall world, it is primarily a body’s defense system. Battle imagery is appropriate for describing the interaction with pathogens and parasites. A person’s blood becomes more potent over time as that person prevails and overcomes pathogens and parasites with its newly formed antibodies in high numbers. Antibodies have the secret locked away to defeat the germ that has invaded. The second infection usually has minimal harm; hence, the “wise” blood is more likely to defeat the enemy. Immunization derives from the brilliant pioneering work of Edward Jenner, a Christian physician, and Louis Pasteur, a creation microbiologist; they solved this time-delay problem for the body. By exposing the body to a weakened or “killed” pathogen, a vaccine shrinks the time for the secondary response of IgG (immunoglobin). Now the body can flood the battle scene with prepared antibodies and can overwhelm intruders. Timing presents by far the biggest challenge to the body’s protective system (Brand and Yancy, 1984). Bodily defenses are strictly an “umbrella” against the “rain” of pathogens and parasites that attack the body. We live in the gap between beneficial colonization and host immune response; otherwise, infection or disease occurs. Vaccination shortens the secondary, intense antibody response. It has “wised-up” to the enemy, and it overcomes the germ, pathogen, or parasite. Antibodies produced in the body represent beauty, complexity, and providential orderliness that exemplify how the body is fearfully and wonderfully made design, glorifying their Creator. Normally, the body loses crucial hours while breaking the code of the new pathogen or parasite while manufacturing antibodies to combat it. With immunization, a prior shot exposes the body to a weakened (attenuated) or antigen component and gives the body prior notice and an upper hand in the cell wars battle. When invaded, the body can flow with a prepared assortment of antibodies and T cells that quickly overwhelm the intruders. Historically, Edward Jenner (a Christian physician) and Louis Pasteur (a creationist) provided the basis for immunization. In more recent times, Dr. Lance Plyler (Samaritan’s Purse physician) saved Dr. Kent Brantley (a Samaritan’s Purse physician and Time Man of the Year) with an Ebola antibody vaccine (ZMapp) in 2014. These represent how the blood “wises” up to enemies (pathogens or parasites) and overcomes their breakout

Suppression of Plasmodium falciparum by serum collected from a case of Plasmodium vivax infection.

BACKGROUND: It has frequently been reported that Plasmodium vivax suppressed Plasmodium falciparum and ameliorated disease severity in patients infected with these two species simultaneously. The authors investigate the hypothesis that immunological responses stimulated by P. vivax may play a role in suppressing co-infecting P. falciparum. METHODS: Sera, taken sequentially from one of the authors (YN) during experimental infection with P. vivax, were added to in vitro cultures of P. falciparum. Cross-reactive antibodies against P. falciparum antigens, and cytokines were measured in the sera. RESULTS: Significant growth inhibitory effects upon P. falciparum cultures (maximally 68% inhibition as compared to pre-illness average) were observed in the sera collected during an acute episode. Such inhibitory effects showed a strong positive temporal correlation with cross-reactive antibodies, especially IgM against P. falciparum schizont extract and, to a lesser degree, IgM against Merozoite Surface Protein (MSP)-119. Interleukin (IL)-12 showed the highest temporal correlation with P. vivax parasitaemia and with body temperatures in the volunteer. CONCLUSION: These results suggest the involvement by cross-reactive antibodies, especially IgM, in the interplay between plasmodial species. IL-12 may be one of direct mediators of fever induction by rupturing P. vivax schizonts, at least in some subjects. Future studies, preferably of epidemiological design, to reveal the association between cross-reactive IgM and cross-plasmodial interaction, are warranted

Developing Approaches Towards the Treatment of Covid-19

In late 2019 a newly identified strain of coronavirus, SARS-CoV-2 emerged, causing a worldwide pandemic of respiratory illness, Covid-19. Covid-19 has drastically transformed the world in numerous ways. The virus is highly contagious and, in some cases, fatal. A successful cure has not yet been discovered and therefore society is urged to take proper precautions to prevent the spread of the potentially fatal virus. This paper analyzes the proper precautions that should be taken as well as the ongoing research that has been done to stop the spread of the virus

Overcoming the challenges of cancer drug resistance through bacterial-mediated therapy.

Despite tremendous efforts to fight cancer, it remains a major public health problem and a leading cause of death worldwide. With increased knowledge of cancer pathways and improved technological platforms, precision therapeutics that specifically target aberrant cancer pathways have improved patient outcomes. Nevertheless, a primary cause of unsuccessful cancer therapy remains cancer drug resistance. In this review, we summarize the broad classes of resistance to cancer therapy, particularly pharmacokinetics, the tumor microenvironment, and drug resistance mechanisms. Furthermore, we describe how bacterial-mediated cancer therapy, a bygone mode of treatment, has been revitalized by synthetic biology and is uniquely suited to address the primary resistance mechanisms that confound traditional therapies. Through genetic engineering, we discuss how bacteria can be potent anticancer agents given their tumor targeting potential, anti-tumor activity, safety, and coordinated delivery of anti-cancer drugs

Spending to Death: Wasteful Government Spending, Transparency Failures, and the Secretive World of Federal Dog Experiments

"The Government Accountability Office has stated, "For decades…the public has been concerned that dogs and cats used in research could be treated inhumanely…"Indeed, in 1966, the U.S. Congress passed the primary federal law governing the use of animals in laboratories -- the Animal Welfare Act -- in response to public outcry about the inhumane procurement and treatment of dogs destined for experimentation laboratories. Specifically, LIFE and Sports Illustrated ran features exposing dealers who collected lost and stolen dogs and sold them to laboratories. At the time, LIFE reported that it received more letters about this article than any other in the magazine's history. Unfortunately, half a century after the creation of the AWA, the federal government secretively still conducts and funds invasive, bizarre, wasteful and deadly laboratory experiments on dogs. The White Coat Waste Project (WCW) reviewed public records that reveal that each year, federal agency laboratories purchase beagles, hounds and mixed-breed dogs-- even puppies -- just to cut them apart, infect them, make them sick, and kill them in taxpayer-funded experiments

Characterizing Neutrophil Behavior in Zebrafish (Danio rerio) in Response to Arsenic and Glucose

The innate immune system recognizes self from non-self and is involved in pathogen clearance. Neutrophils are innate immune cells that quickly migrate to areas of infection or wounding. Neutrophils phagocytize pathogens and produce a respiratory burst that kills infectious agents. However, inappropriate presence and function of neutrophils contributes to many chronic inflammatory diseases. Environmental toxicants and other ingested compounds are known to impact innate immunity and neutrophil behavior. Two compounds of importance to the Maine population are arsenic and glucose, due to the presence of arsenic in Maine well water and the high rate of obesity and diabetes in Maine. Since many Mainers and people worldwide are exposed to arsenic from the environment or have elevated glucose levels, it is important to understand how these compounds impact our health. To test the effects of these compounds on neutrophil behavior, we used a transgenic zebrafish line that allows for observation of neutrophil behavior. Zebrafish embryos were immersed in arsenic- or glucose-containing media and an immune response was stimulated through tail fin amputation or Pseudomonas aeruginosa injection. The total number of neutrophils per embryo was counted and the percentage of neutrophils that migrated to the site of infection or wound in control, arsenic- or glucose-treated zebrafish was calculated. We find that 1% glucose has no effect on the total number of neutrophils or the migration of neutrophils to a wound. However, treatment with 130 ppb arsenic affects neutrophil migration to a wound, with significantly fewer neutrophils being present at wound sites in arsenic treated zebrafish compared to controls

Chemokines (CCL3, CCL4, CCL5) inhibit ATP-induced release of IL-1beta by monocytic cells

ATP and chemokines are among the first inflammatory mediators that can enter the circulation via damaged blood vessels at the site of injury, leading to an activation of the host’s immune response. The main function of chemokines is leukocyte mobilization, guiding immune cells towards the injured tissue along a chemotactic concentration gradient. In monocytes, ATP typically triggers inflammasome assembly, a multiprotein complex necessary for the maturation and secretion of IL-1beta. IL-1beta is a potent inflammatory cytokine of innate immunity, essential for pathogen defense. However, excessive IL-1beta may cause life-threatening systemic inflammation. Here, we hypothesize that chemokines control ATP-dependent secretion of monocytic IL-1beta, by engaging a cholinergic signaling pathway. LPS-primed human monocytic U937 cells were treated with chemokines in the presence or absence of nAChR antagonists or iPLA2beta inhibitors and concomitantly stimulated with the P2X7 agonist BzATP. IL-1beta concentration was determined in the cell culture supernatants. Silencing of the chemokine receptor and iPLA2b gene expression was achieved by transfecting cells with the appropriate siRNA. CCL3, CCL4, and CCL5 dose-dependently inhibited BzATP-stimulated release of IL-1beta, whereas CXCL16 was ineffective. The effect of CCL3 was confirmed for primary mononuclear leukocytes. The inhibitory effect of CCL3 was blunted after silencing CCR1 or iPLA2beta gene expression by siRNA and was sensitive to antagonists of nAChRs containing subunits alpha7 and alpha9/alpha10. U937 cells secreted small factors in response to CCL3 that mediated the inhibition of IL-1beta release. We suggest that CCL chemokines inhibit ATP-induced release of IL-1beta from U937 cells by a triple-membrane-passing mechanism involving CCR, iPLA2, release of small mediators, and nAChR subunits alpha7 and alpha9/alpha10. We speculate that whenever chemokines and ATP enter the circulation concomitantly, systemic release of IL-1beta is minimized