Lecture 7-8

• Global perspective:

  • Declining immunization rates, pathogen resistance to drugs, and emerging infections are current and future challenges
  • Climate change adds a further dimension with potentially serious consequences
  • Fungal infections in Canada have increased in the last decade(s)
• In developed countries, illness and death from infectious diseases greatly declined in the last century
• Malaria:

  • Mosquitoes that can spread it will be able to live in new places due to global warming
• Cholera:

  • Expected to increase with warming
  • Haiti is having big outbreaks, possibly due to inadequate water supply
• Zika:

  • Controlled but not eliminated
• Pathogen versus environment and host defense:

  • Genetic background is important but not the most important
  • Lifestyle and environment mostly make a difference
• SARS-CoV-2:

  • Long COVID affects many organ systems
  • Masks decrease the spread of cough
• Effects of history:

  • Sanitation was the first big breakthrough in dealing with infectious diseases
  • Quarantine started when people realized diseases can spread to others
  • Improved public health and nutrition helped spread of infectious diseases
  • Immunization was an enormous breakthrough
  • Many drugs are now effective against most diseases
• Microbiome:

  • Most are commensal, some are symbiotic, and some are pathogens
  • Important for everyday health and can be deranged in disease
  • Core microbiome and variable microbiome affected by environment, lifestyle, physiology, and health
  • Found everywhere in the body (skin, GI, mouth) with varying compositions
  • Opportunistic pathogens can affect us
  • Virome and mycobiome have similar effects
• Sources of infection:

  • Other humans
  • Insect vectors:
  • Lyme disease is spread by ticks (moving north due to climate change)
  • West Nile virus (spread to Canada), horses are vulnerable to this disease
  • Other species such as rats
  • Food and water:
  • E.g. E. coli in raw beef
• Routes of infection:

  • Airborne transmission through breathing or coughing
  • Spread through hands, the primary way colds and other viruses are transmitted
  • Sexual transmission
  • Blood transmission
  • Transmission across the placenta
• Once in the body, pathogens can spread through nerves, inflammatory cells, lymphatics, or blood to reach other tissues. This is facilitated by receptors on all cells that allow them to recognize specific tissues
• Properties of effective pathogens:

  • Must survive and multiply in the host
  • Resist host defenses, including phagocytosis by host cells
  • Recognize, attach, and alter host cells
  • Reproduce and disseminate
  • Cause injury through the release of exotoxins, endotoxins, or direct cytopathic effects
  • Formation of immune complexes, anti-host antibodies, and cell-mediated immunity
• External host defences:

  • Skin: acts as a barrier, contains fatty acids
  • Airways: have cilia and mucous, many macrophages present
  • GI tract: acidic environment, mucus, microbiome
• Internal host defenses:

  
  

  Pathogen recognition:

  • Normal flora can block pathogen attachment
  • Toll-like receptors and lectin receptors present
  • 
    
  • Innate defenses include epithelial barriers, phagocytes, complement, NK cells, inflammasome
  • Immune system involves adaptive immunity
• Challenges in pathogen resistance:

  • Intracellular pathogens can evade immune system by getting inside cells
  • Pathogens can change their surface properties through antigenic variation
  • Some pathogens inhibit complement activation
  • Pathogens can be resistant to phagocytosis by having features on their surface that make it hard for cells to grab onto them
  • Some pathogens can block the host's recognition system
• Factors contributing to new and emerging diseases:

  • Overpopulation and poverty can lead to disease resurgence
  • Global travel can lead to the emergence of new diseases
  • Overuse of antibiotics can lead to resistance
  • Ignorance and misinformation can result in people not getting vaccinated or not vaccinating their children
• Immunization:

  • Polio:
  • Has been around for a long time
  • Was eradicated with a vaccine but has reemerged
  • Many vaccine-preventable diseases still exist, such as measles, polio, etc.
  • Smallpox has been completely eradicated
  • There have been fraudulent antivaccination campaigns
  • Antiviral drugs are available for influenza, herpes, etc.
• Influenza:

  • Viruses have selective affinity for tracheobronchial epithelial cells
  • Symptoms include: sore throat, runny nose/congestion, fever, headache, myalgia (muscle pain), GI effects, dry cough
  • Complications can include pneumonia, cardiac issues, neurological problems, respiratory problems, pregnancy complications, and musculoskeletal issues
  • Incubation period is 1-4 days
  • Symptoms typically last 7-10 days
  • Viral shedding occurs from day -1 (1 day before symptoms) to a week after recovery
• • Viral action of influenza in the lung involves: nasal cells secreting extracellular vesicles with antiviral properties, so the virus cannot bind to cells and infect it.
  • Release of vesicles is affected by ambient temperatures: cold exposure impairs secretion and function of extracellular vesicles.
• • Antigenic drift and shift play roles in the virus's evolution
• Herpes Viruses:

  • Linear DNA viruses that affect neurons and/or leukocytes
  • 8 types cause human disease
• Vaccination and Therapy:

  • Influenza nomenclature includes virus type, geographic origin, isolate number, year, HA:NA
  • Quadrivalent vaccines target 2 A and 2 B strains
  • Current drugs target the reproductive activity and ability of the virus to leave the cell
• • Masks help with influenza by blocking viruses and warming the air
• influenza virus destroys respiratory epithelial cells:

  • leading to death of infected cells then regeneration
  • antibodies protect against further infection once you are immunized.
• • History of influenza: numerous epidemics and pandemics throughout human history, with a global pandemic in 1918 killing 50 million -- the H1N1 strain did this.
  • Influenza is continually monitored by WHO, infecting about 1 billion people annually
• • Influenza is an RNA virus that continually mutates, with three types: A, B, C.
  • there is also the potential of exchange of variants across different species.
• • Influenza may be linked to Parkinson's disease
• Influenza types:

  • C: doesn’t have neuraminidase and has no genetic variation. Mild infection.
  • B: subject to antigenic drift.
  • A : subject to antigenic drift and shift.
• influenza virus has 8 different segments.
• Antigenic drift versus antigenic shift:

  • Drift: continual small mutations on the antigens on the surface (antibodies less effective but still have an effect).
  • Shift: coming in contact with other strains and is exchanging information with them to create a new strain (that immune system has no way to recognize).
• Life cycle of influenza virus:

  • Recognizes receptors on the human cell, replicated on the inside, then comes back out, and in the process kills the human epithelial cell.
• Roles of viral hemagglutinin and neuraminidase:

  • are two important features on the surface of the viruses that allow it to specifically target the airways, and to allow it to get out of the airway.
  • Hemagglutinin: responsible to recognize the cell, binding to it (binds to sialic acid), and allowing it to get into the cell.
  • Binding can occur through alpha (2,3)-linkage or alpha (2,6)-linkage.
  • Neuraminidase: allows the virus to get out of the cell.
• Hemagglutinin binding:

  (2,3)-linkage: in birds mostly but also in human lower airways.

  (2,6)-linkage: in human upper airways.
• host responses against influenza: antibodies, cell-mediated defenses (T-cells).
• • Influenza can kill if there are inadequate defenses (young, elderly, or immunocompromised), and can generate cytokine storm.   
  • Destroys the cell in 4-6 hours.
• General properties of herpes virus:

  • Cause cell lysis: kill the cell they infect.
  • latency, and reactivation: can never get rid of them.
  • Worldwide distribution and difficult to control
  • Cell-mediated immunity
• • Neurotropic herpes viruses include HHV1 (herpes simplex virus), HSV2, and Varicella-Zoster (Chickenpox / Shingles) – HHV3
• HHV1: herpes simplex virus

  • lesion – cold sores, whitlow.
  • Primary infection: Cell injury in epithelium, enter sensory nerve endings, retrograde transport to trigeminal ganglia.
  • Latent phase: stays in cell bodies of ganglion.
  • Reactivation: anterograde transport using neuronal transport system, to skin and attacks cells.
  • Doesn’t go further since out body is ready to attack it when they come out and reactivate.
  • Can invade brain if immunocompromised: causes encephalitis.
  • There are 31 different strains of it.
• HSV2: very similar to HHV1.

  • Mostly genital infection, and many people don’t realize they have it (no symptoms).
  • Cell-mediated immunity is major host defence