The document discusses the susceptibility of NC/Nga mice to Listeria monocytogenes (LM) infection compared to other mouse strains. Figure 2 shows that NC/Nga mice have decreasing levels of the protective cytokine IFN-γ and increasing levels of the anti-inflammatory cytokine IL-10 after LM infection. This suggests high IL-10 levels may explain the mice's susceptibility. However, Figures 3 and 4 appear to contradict this, so more research is needed to understand IL-10's role in listeriosis.
Parasitic infection and immunomodulation: A possible explanation for the hygi...Apollo Hospitals
Helminthic parasites have a long history of co-evolution with human beings. The incidence of helminthic infection has significantly decreased in developed countries due to better sanitary measures. However, epidemiological data suggest a corresponding increase in the incidence of autoimmune and allergic diseases in association with a reduction in helminthic infections in these societies. The immune response to helminthic infection involves both innate and adaptive processes, with a strongly polarised Th2 response being the most characteristic feature. However, there is a concomitant increase in the functional regulatory T cell responses. This might explain the paradoxical decrease in both Th2-and Th1-mediated diseases such as allergy and immune-mediated inflammatory disorders in populations with increased incidence of helminthic infection. Parasitic infection therefore appears to confer a degree of immunomodulation, and for this reason, utilising helminthic infection as a therapeutic modality for the treatment of allergic and autoimmune disease has been proposed. Improved understanding of the immunologic responses to helminth infection allows these mechanisms to be exploited, enabling manipulation of the immune response in Th1-dominant conditions such as inflammatory bowel disease and multiple sclerosis, and providing a new approach to treatment of these and other inflammatory and allergic conditions.
Dysregulation of macrophage signal transduction by ToxoplasmaIshfaq Maqbool
A brief account of mechanism adopted by Toxoplasma gondii to evade the immune response of the host immune cells particularly macrophages by disruption of macrophage signal transduction
genetic Resistance against gastrointestinal nematodes in sheep: Association w...Ishfaq Maqbool
describes briefly about need of breeding for genetic resistance, candidate genes associated with resistance, genomic regions located on different sheep chromosomes and mechanisms by which the genes act.
HIV-1 Control: Exploiting the HERV-K102 - AFP Immunosenescence ParadigmDr. Marian Laderoute
This slide deck reviews evidence supporting a role of the HERV-K102-AFP immunosenescence paradigm in HIV-1 pathogenesis. It also discusses how this paradigm could be exploited for HIV-1 cure and therapeutic vaccines. Moreover, that human endogenous retrovirus K102 (HERV-K102), which is a foamy retrovirus unique to humans, could be used for gene therapy against HIV-1 as a replication competent (possibly transmissible) protector virus for a sterilizing cure/vaccine. A must read for anyone working on the HIV cure or vaccine.
Parasitic infection and immunomodulation: A possible explanation for the hygi...Apollo Hospitals
Helminthic parasites have a long history of co-evolution with human beings. The incidence of helminthic infection has significantly decreased in developed countries due to better sanitary measures. However, epidemiological data suggest a corresponding increase in the incidence of autoimmune and allergic diseases in association with a reduction in helminthic infections in these societies. The immune response to helminthic infection involves both innate and adaptive processes, with a strongly polarised Th2 response being the most characteristic feature. However, there is a concomitant increase in the functional regulatory T cell responses. This might explain the paradoxical decrease in both Th2-and Th1-mediated diseases such as allergy and immune-mediated inflammatory disorders in populations with increased incidence of helminthic infection. Parasitic infection therefore appears to confer a degree of immunomodulation, and for this reason, utilising helminthic infection as a therapeutic modality for the treatment of allergic and autoimmune disease has been proposed. Improved understanding of the immunologic responses to helminth infection allows these mechanisms to be exploited, enabling manipulation of the immune response in Th1-dominant conditions such as inflammatory bowel disease and multiple sclerosis, and providing a new approach to treatment of these and other inflammatory and allergic conditions.
Dysregulation of macrophage signal transduction by ToxoplasmaIshfaq Maqbool
A brief account of mechanism adopted by Toxoplasma gondii to evade the immune response of the host immune cells particularly macrophages by disruption of macrophage signal transduction
genetic Resistance against gastrointestinal nematodes in sheep: Association w...Ishfaq Maqbool
describes briefly about need of breeding for genetic resistance, candidate genes associated with resistance, genomic regions located on different sheep chromosomes and mechanisms by which the genes act.
HIV-1 Control: Exploiting the HERV-K102 - AFP Immunosenescence ParadigmDr. Marian Laderoute
This slide deck reviews evidence supporting a role of the HERV-K102-AFP immunosenescence paradigm in HIV-1 pathogenesis. It also discusses how this paradigm could be exploited for HIV-1 cure and therapeutic vaccines. Moreover, that human endogenous retrovirus K102 (HERV-K102), which is a foamy retrovirus unique to humans, could be used for gene therapy against HIV-1 as a replication competent (possibly transmissible) protector virus for a sterilizing cure/vaccine. A must read for anyone working on the HIV cure or vaccine.
That’s important because right now, doctors have to rely on a set of 11 criteria, which can overlap with many other diseases, to try to make a diagnosis.
“It is one of the most complex clinical diagnoses,” says Pascual, who is also a practicing pediatric rheumatologist.
“It might lead to better diagnostic tests, but we don’t know that yet,” Pascual says. Other experts say the discoveries will most certainly lead to new drug targets.
Systemic lupus erythematosus (also called SLE or lupus)
is an autoimmune condition. The normal role of your
body’s immune system is to fight off infections and
diseases to keep you healthy. In an autoimmune disease
like lupus, your immune system starts attacking your
own healthy tissues. For some people lupus may just
affect the skin and/or joints. In other people the lungs,
kidneys, blood vessels,
That’s important because right now, doctors have to rely on a set of 11 criteria, which can overlap with many other diseases, to try to make a diagnosis.
“It is one of the most complex clinical diagnoses,” says Pascual, who is also a practicing pediatric rheumatologist.
“It might lead to better diagnostic tests, but we don’t know that yet,” Pascual says. Other experts say the discoveries will most certainly lead to new drug targets.
Systemic lupus erythematosus (also called SLE or lupus)
is an autoimmune condition. The normal role of your
body’s immune system is to fight off infections and
diseases to keep you healthy. In an autoimmune disease
like lupus, your immune system starts attacking your
own healthy tissues. For some people lupus may just
affect the skin and/or joints. In other people the lungs,
kidneys, blood vessels,
Sepsis which is commonly called as septicemia is one of the most dreadful and vulnerable life threatening disease which is quite uncommon in popularity. Around the world 1.8 million cases and in India there is 30% of nosocomial infectious patients get infected per annum accounted epidemiologically. It happens by gradual steps which is based on the incidence of the physiological and biochemical malfunctions from which septic shock is the last severe step. It is not depend on the single specific pathway dysregulation rather regulated by multi biological pathways. Various malfunctions in regulated systems like paralysis of neutrophils, higher production of proinflammatory products, diversion of adaptive immune cells like TH1 and TH2, apoptosis of lymphocytes and dendritic cells leads to sepsis. Complement anaphylatoxin C5a plays a major mediator of inflammatory response and dysregulation of plasmatic cascade. Disruption of any connecting linkers between the coagulation, complement and fibrinolysis leads to inhibition of anticoagulation mechanism. Adrenergic and cholinergic inflammatory pathway which regulates the inflammatory response get altered. In biochemical point of view endothelial dysfunction occurs mainly due to the formation of reactive oxygen species (ROS) and other components, Properdin level also get downregulated. Although much progress has been made in the treatment of inflammatory disease, the continued high mortality in septic shock is a sobering reflection of current therapeutic approaches. Nevertheless, increased understanding the molecular mechanism of various factors, connecting links and the multi effectors of sepsis can provide for better path to conquer sepsis in maximum ways.
This slide covers briefly how intracellular and extracellular bacteria elicits an immune response, how bacteria evade from the immune system, what complement system is, opsonization, neutralisation, septic shock, sepsis, superantigens, phagocytosis, interleukins, Toll-like receptors, a list of diseases caused by bacterias and their names etc.
Presentation of the Philippine Goat Industry to the Meat and Milk Hygiene Class of Prof. Tadasu Urashima of Obihiro University of Agriculture and Veterinary Medicine
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
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ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
1. アバオラリーネルビルバオ February 26, 2010
Infection Immunology 川本先生
Why is NC/Nga Mice Highly-Susceptible to LM Infection
In the lecture that was presented on the Function of Immune Responses Against
Infection last January 27, 2010, we were asked about our hypothesis on the role of
Interleukin (IL)-10 in Listeriosis. Before I discussed the figures given, I would like to
define some important terms of the report.
According to Wikipedia, Listeria monocytogenes (LM) is a facultative intracellular
bacterium that is the causative agent of Listeriosis. It is one of the most virulent food
borne pathogens with twenty (20) to thirty (30) percent of clinical infections resulting
in death. Responsible for approximately 2,500 illnesses and 500 deaths in the
United States (U.S.) annually, listeriosis is the leading cause of death among food
borne bacterial pathogens with fatality rates exceeding even Salmonella and
Clostridium botulinum.
LM is a Gram-positive bacterium, in the division Firmicutes, named for Joseph Lister.
Motile via flagella at 30 °C and below but usually not at 37 °C, LM can instead move
within eukaryotic cells by explosive polymerization of actin filaments (known as
comet tails or actin rockets). Studies suggest that up to 10% of human
gastrointestinal tracts may be colonized by LM.1 Nevertheless, clinical diseases due
to LM are more frequently recognized by veterinarians, especially as meningo-
encephalitis in ruminants. More recently, LM has been used as the model organism
to illustrate the patho-biotechnology concept.
Meanwhile, Wikipedia defined Interferon-gamma (IFN-γ) as a dimerized soluble
cytokine that is the only member of the type II class of interferons. This interferon
was originally called macrophage-activating factor, a term now used to describe a
larger family of proteins to which IFN-γ belongs. IFN-γ, or type II interferon, functions
as a cytokine that is critical for innate and adaptive immunity against viral and
intracellular bacterial infections and for tumor control. Aberrant IFN-γ expression is
associated with a number of auto inflammatory and autoimmune diseases. The
importance of IFN-γ in the immune system stems in part from its ability to inhibit viral
replication directly, but, most important, derives from its immunostimulatory and
immunomodulatory effects. IFN-γ is produced predominantly by natural killer (NK)
and natural killer T (NKT) cells as part of the innate immune response, and by CD4
and CD8 cytotoxic T lymphocyte (CTL) effector T cells once antigen-specific
immunity develops.
And lastly, Interleukin-10 (IL-10), also known as human cytokine synthesis inhibitory
factor (CSIF), is known as an anti-inflammatory cytokine. This cytokine is produced
primarily by monocytes and to a lesser extent by lymphocytes. This cytokine has
pleiotropic effects in immunoregulation and inflammation. It down-regulates the
expression of Th1 cytokines, MHC class II antigens, and costimulatory molecules on
macrophages. It also enhances B cell survival, proliferation, and antibody
production.
1
Ramaswamy, Vidhya and Cresence, Vincent Mary. "Listeria - Review of Epidemiology and
Pathogenesis." J Microbiol Immunol Infect. (2007). 40:4-13
1
2. This cytokine can block NF-κB activity, and is involved in the regulation of the JAK-
STAT signaling pathway. Knockout studies in mice suggested the function of this
cytokine as an essential immunoregulator in the intestinal tract.2
A study in mice has shown that interleukin-10 is also produced by mast cells,
counteracting the inflammatory effect that these cells have at the site of an allergic
reaction.3 It is capable of inhibiting synthesis of pro-inflammatory cytokines like IFN-
γ, IL-2, IL-3, TNFα and GM-CSF made by cells such as macrophages and the Type 1
T helper cells. IL-10 also displays potent abilities to suppress the antigen
presentation capacity of antigen presenting cells. However, it is also stimulatory
towards certain T cells, mast cells and stimulates B cell maturation and antibody
production.
In Figure 1, a dose of LM 8.0 x 105 was administered per head to the NC/Nga, BALB/
c, and C57BL/6 mice. It can be seen that until day 3 post infection, the three (3) mice
have a survival rate of 100%. However, by day 4 post infection, the survival rate of
the NC/Nga mice went down to around 10%. And finally, by day 5 post infection,
there were no more survivors in the NC/Nga mice (unlike in the BALB/c mice and
C57BL/6 mice). In the day 5 post infection, BALB/c mice had a survival rate of 80%
while C57BL/6 mice, 100%.
Figure 1. NC/Nga Mice is Highly Susceptible to LM Infection
2
"Entrez Gene: IL10 interleukin 10"
3
Grimbaldeston, MA, et. al. (October 2007). "Mast cell-derived interleukin 10 limits skin pathology in
contact dermatitis and chronic irradiation with ultraviolet B". Nat. Immunol. 8 (10): 1095–104.
2
3. In the case of Figure 2, the IFN-γ level in NC/Nga mice increased to around 13,000
during the day 1 post infection. However, it decreased to around 12,000 during the
day 2 post infection. And finally, it further decreased to 11,000 during the day 3 post
infection. After day 3 post infection, there was no more data on IFN-γ as the NC/Nga
Mice have died. This may lead to a hypothesis that the IFN-γ is important to the
survival rate of NC/Nga Mice being subjected to Listeriosis.
The analysis for the role of IL-10 is the opposite of that of the IFN-γ. The serum level
of IL-10 for NC/Nga mice is at 500 during the day 1 post infection. It increased to
around 600 serum levels during the day 2 post infection. Then, it shot up to the
3,000 level by day 3 post infection. However, by day 4 post infection, all the NC/Nga
mice have died. It seems that the presence of significantly high serum levels of IL-10
is detrimental to the survival rate of NC/Nga mice.
Figure 2. Increased serum levels of IL-10 in NC/Nga Mice
The results of IL-10 in Figure 1 are consistent with the results of a similar study on
the Role of IL-10 in a Neonatal Mouse Listeriosis Model that was done in 1999. This
study was undertaken to test the hypothesis that altered IL-10 production plays a role
in the increased susceptibility of neonates to listeriosis. 4 Plasma IL-10 levels were
measured in neonatal and adult mice at various times after infection with Listeria
monocytogenes. Collectively, the data of the study suggested that an overproduction
of IL-10 by macrophages may at least partially explain the increased susceptibility of
neonates to listeriosis (and provide further evidence that cytokine production is
different in adults and neonates). The conclusion of the study was that neonatal
mice produce high IL-10 levels during listeriosis or after the injection of killed
bacteria. Overproduction of the cytokine is apparently detrimental during listeriosis,
but may be beneficial in infections by other pathogens.
4
Francesco Genovese, et. al., Role of IL-10 in a Neonatal Mouse Listeriosis Model, The Journal of Immunology, 1999, 163,
2777-2782.
3
4. Meanwhile, according to another study, high doses of Listeria monocytogenes
overcome the ability of a normal mouse to control the infection, due to massive
bacterial replication. Treatment with an anti-interleukin 10 (IL-10) receptor
monoclonal antibody prevented the fatal course of infection with high doses of
bacteria. This work showed that blocking the receptor for IL-10 may have useful
therapeutic applications.5
In Figure 3 on the next page, it can be seen that an Anti-IL-10 was administered to
the NC/Nga mice to see its effects. In this scenario, an LM of 7.4 x 104 per head was
administered. The result of this figure is not conclusive. It is also inconsistent with
Figure 2. In fact, the decreased serum levels of the IL-10 led to a 0% survival rate by
day 4 post infection (shown by the red line). In the case of the control group (the
blue line), survival of the NC/Nga mice remained steady at 40% from day 6 to day 14
post infection because of the presence of IL-10.
Figure 3. Effects of the Anti-IL-10 Dosage to NC/Nga Mice
In the case of Figure 4 (on the next page), the administration of the IL-10 to the three
types of mice (i.e. NC/Nga, BALB/c, and C57BL/6J) led to their increased survival
rates. In this model, an LM of 4.2 x 105 per head was administered. In the case of
BALB/c and C57BL/6J mice, survival rates increased to 100%. This happened at
day 3 post infection for BALB/c mice while for C57BL/6J, at day 5 post infection. The
result of Figure 4 is also inconsistent with the result of Figure 2.
5
Regina A. Silva and Rui Appelberg, Blocking the Receptor for Interleukin 10 Protects Mice from Lethal Listeriosis, 2001,
American Society for Microbiology
4
5. Figure 4. Effects of IL-10 Dosage to NC/Nga, BALB/c, and C57BL/6J Mice
The role of IL-10 in listeriosis is not entirely clear. Anti-IL-10 treatment resulted in
increased bacterial replication and lethality late in the course of infection, after
producing an early improvement in another study.6 In another report, however, adult
IL-10-deficient mice showed increased resistance to L. monocytogenes,7 while
administration of r IL-10 severely decreased innate defenses against the organism.8
Based on Figure 2 alone, the conclusion would be that the presence of IFN-γ
increased the resistance of the NC/Nga mice against listeriosis. On the other hand,
significantly high levels of IL-10 made the NC/Nga mice highly-susceptible to
Listeriosis. The results of the other figures above (Figures 3-4) did not show
conclusive evidence on the Figure 2 hypothesis. In this regard, additional studies
should be carried out to further understand the real role of IL-10 in listeriosis.
6
25. Wagner, R. D., N. M. Maroushek, J. F. Brown, and C. J. Czuprynski, 1994, Treatment with anti-interleukin-10 monoclonal
antibody enhances early resistance to but impairs complete clearance of Listeria monocytogenes infection in mice, Infection
Immunology, 62:2345.
7
26. Day, W., G. Ko¨hler, and F. Brombacher,1997, Both innate and acquired immunity to Listeria monocytogenes infection
are increased in IL-10-deficient mice, Journal of Immunology, 158:2259.
8
27. Kelly, J. P., and G. J. Bancroft, 1996, Administration of interleukin-10 abolishes innate resistance to Listeria
monocytogenes, European Journal of Immunology, 26:356.
5