Emerging Disease/History of Immunology (MT1)

Define: Immunology

How our body recognizes itself as well as soluble and cellular defenses to diseases

Define: Disease

The pattern of response of a living organism to some form of injury

What are the universal mechanisms of the body to repair tissue (signs of inflammation)?

Redness, Swelling, Heat, Pain, and Loss of function

What did Thucydides observe about the plague?

Individuals who were previously infected and survived were less likely to be re-infected and they rarely died. (a primitive understanding of immunity)

What did the first smallpox vaccine consist of? Which cultures came up with them?

Chinese - Inhaled ground small pox scabs
Turks - Inserted small pox scabs into small cuts

How did Lady Mary Wortley Montague effect immunology/vaccines in the west?

She allowed her children to be vaccinated against small pox using the methods the British believed to be barbaric, allowing it to gain popularity in the West

How did the small pox from cowpox vaccine change immunology?

The development of vaccines from cow pox to treat small pox created a field of medicine around vaccines/immunity

What were Koch's 4 postulates?

- The organism should only be present in individuals suffering from disease
- The organism must be able to be grown in a pure culture
- Culture-grown organisms must cause disease when injected into a susceptible animal
- Re-isolated organism must be identical to the original organism

What did Koch discover?

Discovered/Identified Bacteria as the cause of many illnesses

What did von Behring discover?

The transfer of fluids from one immunized animal to another granted protection from even lethal doses, led to HUMORAL IMMUNITY

What did Metchnikoff discover?

Observed cells from sea urchins absorb particulates (phagocytosis), led to CELL MEDIATED IMMUNITY

Define: Endemic

The constant presence/usual prevalence of a disease in a population in a geographic area

Define: Epidemic

A sudden increase in the number of cases (above what is normally expected in that population and area)

Define: Pandemic

An epidemic that has spread over several countries or continents, usually affecting large numbers of people

Define: Outbreak

Same definition as an epidemic, but often restricted to a smaller geographic area

Define: Cluster

Cases grouped in a place and time, that are above endemic numbers, often originating from a single source

Define: Sporadic

A disease that occurs infrequently and irregularly

Explain the six classifications of pandemics (specifically influenza)

1. No new animal influenza that is transmissible to humans reported
2. Animal influenza that is transmissible to humans is circulating (potential threat)
3. Sporadic or small clusters of disease reported in humans, but no human-human transmission
4. Human-human transmission, community level outbreaks
5. Two or more countries affected in one WHO region
6. Multiple WHO regions are affected

What caused the shift from bacterial to viral infections?

1. The development of antibiotics
2. Better sanitization practices
3. A better understanding of bacteria

Explain the naming of pathogens. Use A/California/7/2009(H1N1) as an example.

See image.

What makes up a viral capsid?

HA (hemagglutinin) and NA (neuraminidase)

What is the purpose of Hemagglutinin (HA)?

Allows the virus to bind to host cells (reason for some viruses affecting upper vs. lower airways)

What is the purpose of Neuraminidase (NA)?

Allows for the release of viruses from the cell surface (important for entry into cells + spread of progeny viruses)

How is single stranded RNA beneficial to viruses?

Single stranded RNA is very unstable, which results in more mutations/genetic shuffling.

Define: Antigenic Drift

Genetic variation in viruses, arising from the accumulation of mutations in the virus genes that alter virus-surface proteins that host antibodies recognize. (maintains some similarity)

Define: Antigenic Shift

Reassortment leading to completely novel pathogens, allows pathogens to jump species

How does reassortment lend an advantage to viruses?

Pathogens that would not have caused symptoms in humans reassort with human viruses to be transmissible and symptomatic in humans

Why has there been an increase in reassortment?

- Reluctance to report newly-detected pathogens
- Travel brings new pathogens into contact with farm animals
- Increasing population density = higher food demands = high density, mixed species farming

Where did coronaviruses originate? (Vector)

Bats, novel strains occurring via reassortment allowed it to jump species and mutate until it could infect humans.

Is it best to be proactive or reactive in pandemic research?

Proactive, it can prevent pandemics from ever occurring.

Define: Horizontal Gene Transfer

MGE DNA that is transferred from one bacteria to another strain, rapid acquisition of large amounts of genetic information (occurs without mitosis).

MRSA possesses a plasmid (MGE) that contributes to its antibiotic resistance, explain where it came from and the mechanism of resistance

MGE likely came from a strain of staph in pigs (via HGT). It carries the gene mecA, which codes for a protein that is unable to bind to β-lactam containing antibiotics (penicillin). Thus allowing it to thrive even in the presence of antibiotics.

Define: Nosocomial Infection

An infection acquired/originating in a hospital setting.

Define: Emerging Disease

One that has appeared in a population for the first time, or that may have existed previously but is rapidly increasing in incidence or geographic range

What are some reasons for the appearance of emerging diseases?

- Genetic mutation/diversification (antigenic shift vs. drift)
- Drug resistance
- Climate change
- Human behaviour (travel, reduced vaccination, etc)

Define: Epidemiology

A branch of medicine that investigates the origins and conditions of the spread of disease (epidemics)

How do HA-MRSA and CA-MRSA differ?

HA: Hospital acquired, developed in the 1960 after the invention of methicillin, found in immunocompromised patients
CA: Community acquired, developed in the 1990s among intravenous drug users, crowded populations, unsanitary tattoos.

Define: Virus Reassortment

Occurs when multiple viruses with segmented genomes infect the same cell. They then swap genetic segments to form a novel virus. Which leads to new or modified virulence traits (including the ability to jump species)

If a virus had no hemagglutinin, how would it affect the function of the virus?

Without hemagglutinin, the virus cannot bind to the host cells and cannot infect the host.

If a virus had no neuraminidase, how would it affect the function of the virus?

Without neuraminidase, the virus can bind to host cells, but cannot exit the host/spread progeny.

Define: Mobile Genetic Elements (MGEs)

Discrete segments of DNA that move as units from one location to another within other DNA molecules.

What has led to the increase in MRSA infections?

We selected for it. Our excessive use of antibiotics have killed off normal MSSA strains, leaving only the evolved/resistant MRSA behind.

How have changing weather patterns impacted the prevalence of malaria?

- Increased rainfall creates abundant breeding grounds
- Reduced rainfall/excessive heat has caused both humans and mosquitos to relocate, causing much overlap in habitats
- Increasing temperatures have increased the range of mosquito habitats

Explain: Malaria. What causes it, how is it transmitted?

Malaria is caused by the Plasmodium parasite which is carried by the vector; Anopheles mosquitos. Malaria infects our red blood cells (sickle cell individuals are immune). Malaria has existed since before humans did.

What factors have led to an increase in Lyme Disease?

- The density of tic (lyme disease vector) populations have increased due to favourable living conditions
- The habitats of deer and other tic-carrying animals are overlapping with human areas (more contact)
- We are testing and actively looking for lyme disease (we weren't before)

How does our immune system fight Mycobacterium Tuberculosis?

TB is consumed by macrophages in the lungs, however the macrophages fail to kill TB. More macrophages surround the infected cell, creating a physical barrier preventing the infected macrophage from spreading. This barrier is called a granuloma.

How is Mycobacterium Tuberculosis capable of re-infecting patients?

- If the immune system weakens or another more pressing threat is present, the granuloma may break down leading to the escape of the infected macrophage and the spread of TB.

What advancements led to the reduction in Mycobacterium Tuberculosis cases?

- Identification of cause (Mycobacterium Tuberculosis bacteria)
- Improved sanitation
- Pasteurization of milk (TB was frequently found in unpasteurized dairy)
- Discovery of streptomycin antibiotic
- Vaccination of at-risk groups (Indigenous populations)
- Development of pneumothorax technique
- Isolating of the infected in sanitoriums

Define: Pneumothorax Technique

The infected lung is collapsed, causing the immune system to pour resources into repairing the lung (thus irradicating TB within the lung). Once TB is no longer present, the lung is re-inflated.

How did the HIV/AIDS epidemic aid in the resurgence of Mycobacterium Tuberculosis?

Immunodeficient hosts (from HIV) were prone to infections and often given multiple short rounds of antibiotics to restore health. These antibiotics were not sufficient to kill TB, leading to the multiple drug-resistant TB we see today.

What has caused Mycobacterium Tuberculosis to re-emerge?

- Overcrowding promotes the spread of TB (lots of people living in unsanitary, moist, packed environments)
- Malnutrition causes latent infections to become active
- Unequal/poor access to healthcare

Will we need annual coronavirus shots like we do for influenza? Why or why not?

No. Influenza is capable of developing rapid mutations and reassortments leading to new influenza strains. Coronaviruses mutate slowly, so we likely will never have yearly Covid shots.

Why was microcephaly observed as a result of Zika virus in Brazil, but not in Africa/the South Pacific?

Zika is endemic to Africa and the South Pacific, childhood exposure to Zika results in immunity in pregnant women later on, thus microcephaly was not observed. Zika was new to Brazil, there was no previous immunity leading to high rates of microcephaly among infants born to Brazilian mothers.

How is Zika virus spread?

Vectors (Mosquitos) and Sex

What strategies can we use to improve the future of emerging diseases?

- Limit the generation of new diseases
- Improve the detection/containment of new diseases
- Develop new therapies/vaccines

How can we limit the generation of new diseases?

- Antimicrobial stewardship (responsible use of antibiotics) - Climate/environment awareness,
- Responsible farming practices (reduced use of antibiotics, limiting runoff from farmlands, separating species)
-Limit contact between species, limit wild meats, improve sanitation and reduce tourism to these areas. (Open markets are breeding grounds for new diseases)

How can we improve the detection/containment of disease?

- Better surveillance
- Honest reporting (Don't be like Italy)
- International cooperation

How can developing therapies and vaccines help stop disease?

We can develop new universal antivirals, new antibiotics, and vaccine platforms.

Proactive, rather than reactive, research is needed to stop spread before it starts.

Explain: Staphylococcus Aureus, the (SA of MRSA)

- Part of our normal skin flora, 20% (50% in Canada) have non-pathogenic nasal colonization
- Infection in cuts causes puss-filled infection
- If infection doesn't clear, or its a virulent strain, develops into a large lesion, can be life threatening and cause necrosis
- Leading cause of sepsis