BIOL 0510 - Microbial Pathogenesis

What is pathogenesis?

the steps involved in the origin and development of a disease

What is pathogenicity?

the ability of an organism to cause disease or induce damage to the host

What can virulence refer to?

the degree of pathogenicity

What are the four main modes of microbial transmission?

respiratory, ingestion of contaminated food or water, insect bites, blood or body fluid

Provide examples of illnesses spread through inhalation

flu, measles and COVID-19

Provide examples of illnesses spread through insect bites

west nile disease and lyme disease

Provide examples of illnesses spread through blood and bodily fluids

HIV and hepatitis

Provide examples of illnesses spread through contaminated food or water

Rotaviruses

What is zoonosis?

the transmission of an infectious disease from non-human organisms to humans

What’s an example of a pathogen that uses cell lysis to cause disease?

polio virus

What effect does polio virus have on the body?

paralysis, bone deformities and weakening of muscles, particularly in children

How does polio virus use cell lysis?

It has tropism for motor neurons in the spinal cord. When it reaches the CNS, it kills the neurons connected to muscles so muscles don’t receive the signals that they should and they atrophy

Why is it hard to know the true number of people infected with polio virus?

majority of the cases are asymptomatic

Provide an example of a pathogen that uses inflammation and cell dysfunction to cause disease

ebola

What virus family is ebola part of?

Filoviridae

How does ebola spread?

via body fluids

What is the proposed chain of infection for ebola?

fruit bats (asymptomatic resevoir) to great apes to humans

When was the first outbreak of ebola?

1976

How does ebola cause inflammation?

When the virus gets into the bloodstream, it invades monocytes and replicates. This causes monocytes to produce potent cytokines leading to inflammation

Why does ebola lead to vascular instability and internal bleeding?

the virus attaches to blood vessels and causes endothelial cells to detach from blood vessels

What are some of the bodily impacts of ebola?

liver damage and hypovolemic shock which can lead to severe blood and fluid loss and even organ failure

What is inflammation?

the body’s natural immune response to injury, infection or irritation

What are the 5 main signs of inflammation?

pain, heat, redness, swelling and loss of function

What is the purpose of inflammation?

promotion of healing and clearing of an infection but it can cause damage

Why are infections deeper in the lungs more severe?

the lower respiratory tract is where gas exchange is done so the effects of infection like fluid buildup can limit the effectiveness of gas exhange

Prrovide examples of lung infections

bronchitis, pneumonia and influenza

What is a cytokine storm?

a severe life threatening immune reaction where the body release too many inflammatory cytokines

What are diseases that are associated with cytokine storms?

sepsis, ebola, bird flu and severe COVID-19

What is a common treatment for a cytokine storm?

steroids

What is meningitis?

swelling and irritation of the membranes covering the brain and spinal cord (meninges)

What is the most common form of meningitis?

viral; fungal is rare can be deadly like bacterial

Why is it really bad is babies get meningitis?

their blood-brain barrier is still being developed

What usually causes pelvic inflammatory disease?

chronic infection of Chlamydiae trachomatis and Neisseria gonnorhoea

Why is pelvic inflammatory disease a major cause of infertility?

it can cause the fallopian tubes to constrict and lead to fibrosis

Which kind of immune cell does HIV have a tropism for?

T helper cells which it eventually starts to kill. This allows for opportunistic infections which can be deadly

What are some of the effects of measles?

hearing loss, pneumonia, encephalitis and immune amnesia

How does measles cause immune amnesia?

To fight measles, the body generates lots of antibodies against measles and leads to a deficient immune response against other pathogens for two years or more

What should measles survivors do post-recovery?

get vaccinated against lots of diseases again

What percentage of cancer cases were attributed to a carcinogenic infection?

15%

What is cancer?

Uncontrolled growth of abnormal cells in the body due to increased cell proliferation, metastasis and decreased apoptosis

What did Dr Peyton Rous win the Nobel Prize for?

showing that viruses can cause cancer

How did Rous show that viruses can cause cancer?

Rous ground up chicken sarcomas, centrifuged them to remove the solid material, and injected the remaining liquid into chicks. The chicks developed sarcomas

What is an oncogene?

a mutated gene that promotes cell proliferation and blocks apoptosis

What’s an example of an oncogene?

v-Src in Rous sarcoma virus (RSV)

What are tumour suppressor genes?

genes that block cancer progression by surveying the genome

What are examples of tumour suppressor genes?

p53 and Rb

What are some of the ways bacterial and viral genes can alter host cell behaviour?

increasing cell proliferation, increasing cell replication, blocking apoptosis, activating signalling pathways for cell migration

What can human papillovirus cause?

cervical cancer, throat cancer and esophagus cancer

How does HPV cause cancer?

viral genes E6 and E7 bind and block tumour suppressor genes Rb and p53 so that the host cells they infect can continue acting as their viral factory for longer

Which bacterium causes 60-90% of gastric cancers?

H. pylori

In 20% of people infected with H. pylori was is the effect?

stomach ulcers

If the H. pylori in a person’s stomach has the CagA gene, how much does their risk of developing gastric cancer increase by?

6 times

What is the effect of the CagA gene?

changes in cytoskeleton, breaking of cell junction and transcriptional activation of many genes including ones for inflammatory cytokines

What is Hepatitis C?

a chronic and contagious lytic infection in the liver

What does Hepatitis C virus do?

the lytic nature of the virus leads to increased cell turnover and cell death

What’s the effect of the large scale immune response to Hepatitis C virus?

the large scale immune cell invasion leads to increased inflammation and oxidative stress which can cause DNA damage

What does Hepatitis C virus increase risk of?

cancer and cirrhosis (scarring of the liver as cells stop regenerating)

Which type of cell does Epstein Barr virus infect?

B cells

What family of viruses does Epstein Barr Virus belong to?

Herpesviruses

What does EBV do?

make double stranded breaks in DNA whilst integrating its genome

Where does EBV like to make ds breaks?

chromosomes 8 and 14 and translocates sections of those genes onto each other.

What is an example of an endotoxin?

LPS which is released when bacteria break down or divide

What does LPS do?

stimulate an immune response but not cellular damage

What are exotoxins?

soluble chemicals released by bacteria that directly harm or kill host cells

What exotoxins does Staphylococcus have?

hemolysin, coagulase to break down clots and leucocidin to lyse leukocytes

What is streptokinase?

a toxin released by Streptococci to break down clots - a former treatment for stroke and heart attack patients

What does a Type I secretion system do?

Release toxins into the extracellular environment

What do secretion systems 2-4 do?

inject toxins into host cells

What are effector proteins?

proteins released from a bacterium that manipulate or subvert the host cell but don’t kill it

What’s an example of an effector protein?

Yop proteins released by Yersinia

What do Yop proteins do?

inhibit phagocytosis, block lymphocyte proliferation and the release of cytokines

What are AB exotoxins?

an exotoxin with an active unit for potency and a binding unit for entry

Provide examples of AB exotoxins?

anthrax, shiga, cholera, tetanus and botulinum toxins

What is the effect of botulinum toxin?

the release of acetycholine is blocked so muscles stay in a relaxed state and can’t contract

What is the effect of tetanus toxin from Clostridium tetani?

release of inhibitory neutrotransmitters GABA and glycine is prevented which causes muscle spasms