Microbial Virulence Flashcards
What are ‘indigenous biota’?
Micro-organisms that lie on our body surfaces, both internal and external, and are mainly bacteria
What are indigenous biota constantly in?
Dynamic reflux
What do normal clearing systems provide?
A semi-sterile environment in the upper GI tract and lower respiratory tract
What is the importance of the bodys clearing system?
Although normal microbiota have low pathogenic potential, any change can lead to mild to life threatening endogenous infection
What is the principle reserve for our microbiota?
The GI tract
What may breaches of the GI tract lead to?
Heavy soiling of normally sterile sites
What does virulence refer to?
The relative capacity of a microbe to cause damage to a host
What can the concept of virulence occupy?
The full spectrum of non-pathogenic to highly pathogenic, which can result in life-threatening conditions
Is there variety in virulence between strains of pathogens?
Yes
What causes variety in virulence between strains of pathogens?
Changes in virulence factor repertoire and mobile genomic content
Give an example of a pathogen that has variety in virulence between its strains?
S Aureus
What is a pathogen defined as?
A microbe capable of causing host cell damage
What can pathogens be categorised into?
- Obligate pathogen
- Typical pathogen
- Opportunistic pathogen
Where are obligate pathogens found?
Only in humans associated with disease
Give an example of an obligate pathogen
Mycobacterium tuberculosis
What is meant by a typical pathogen?
Can be present as part of the normal biota, yet frequently cause disease
Give an example of a typical pathogen
H. Influenzae
Where is an opportunistic pathogen seen?
Only in immunocompromised patients, breaches of normal defences, or congential defects
Give an example of an opportunistic pathogen?
S. Epidermidis
What are the two main ways in which an individual will encounter a pathogen?
- Endogenous
- Exogenous
What happens in endogenous infections?
The normal microbiota can multiply and develop
What are endogenous infections due to?
Disruption of normal defences
What happens in exogenous infections?
Infecting bacteria have been acquired from an external source, and is not part of the natural microbiota
Where can pathogens come from?
- Food
- Water
- Aerosols
- Blood
- Bodily fluid
What does the natural surface defence mechanism provide?
A formidable barrier
What can a break in the natural surface defence mechanism cause?
Pathogenic infection
What are the main points of entry for bacteria?
- Ingestion
- Inhalation
- Sexual transmission
- Vertical transmission
- Vectors
- Trauma
How can many pathogens cause disease?
Through toxin-mediated release
What do some pathogens require to cause disease?
Colonisation of the host
What does colonisation of the host require?
- Resistance to the flushing mechanism
- Compete with the normal microbiota for colonisation of the mucosa
Give an example of a flushing mechanism of the body?
The muco-ciliary escalator
What features might a pathogen have to help them successfully colonise a host?
- Pili
- Fimbriae
- Flagella
What is the purpose of pili and fimbriae?
Bind to host cell
What are flagella used for?
Aid bacterial mobility
What are flagella vital for?
The early phase of infection, especially in the GI tract
By what mechanisms can bacterial cells gain access to the host cell?
- Simple endocytosis
- Using molecular syringe to secrete effector proteins into the cell to allow for its uptake
- Degrading enzymes for connective tissue or neighbouring cells can be released, and the bacterial cells can stay in the tissue and multiply
What happens once bacterial cells have gained access to the host cell?
Toxins can be released, or there is potential for spread of the organisms into the bloodstream to cause pathogenic effects systemically
How can bacteria cause pathogenic effects systemically?
Bacteria can stay in the tissue and release toxins into the bloodstream
How can bacteria cause damage?
- Wide range of degrading enzymes
- Secrete cytolysins
What degrading enzymes can be secreted by bacteria?
- Proteases
- DNAases
- Collagenases
- Lipases
What is the effect of degrading enzymes secreted by bateria?
They cause tissue damage
What do cytolysins do?
Damage the cytoplasmic membrane of the host cells, and cause cell death
What are toxins?
Bacterial products that harm tissues or affect key biological events at local or distant sites, working in small concentrations
What are the main types of toxins?
- Endotoxins
- Exotoxins
- Superantigens
What are endotoxins also known as?
Lipopolysaccharides
Where are endotoxins found?
In the outer membrane of Gram negative bacteria
When can endotoxins be present in high levels?
During infection
What do endotoxins do?
Promote inflammatory responses in individuals
What is the result of the endotoxin promoted inflammatory response?
- Fever
- Vasodilation
What can endotoxins promote in very high concentrations?
Systemic inflammatory response syndrome (SIRS)
What can endotoxins produce if left untreated?
- Septic shock
- Fever
- DIC
- Multi-organ failure
What are exotoxins?
Proteins produced by bacteria that disrupt the function or kill target cells
How can exotoxins spread?
Systemically, even if the bacteria producing them is only locally located
How do superantigens exert their effects?
By binding to T cell receptors and MHC class II, and mimicking the effects of antigen presentation
What do the effects of superantigens produce?
An inflammatory response with SIRS like pathology
What is a good example of a toxin mediated reponse?
The cholera toxin
What is the cholera toxin composed of?
An A and 5 B subunits
What do the B subunits of the cholera toxin do?
Activates GM1-ganglioside receptor on the intestinal cell
What does the activation of the GM1-ganglioside receptor on the intestinal cell wall allow?
Endocytosis of the toxin
What happens when the cholera toxin has been endocytosed?
It is cleaved
What does the A subunit of the cholera toxin do?
Activate adenylyl cylase
What is the result of the cholera toxin activating adenylyl cylase?
It causes an increase in cAMP, which stimulates the efflux of ions and thus the efflux of water
What is the result of the efflux of water caused by the cholera toxin?
- Severe dehydration
- Electrolyte imbalance
What can the inflammatory response to a virus do?
Produce collateral tissue damage
What is the collateral tissue damage caused by the inflammatory response to viruses mediated by?
- Neutrophils
- Macrophages
- Complement
What can result from swelling caused by viruses?
Compromised tissue perfusion
Why can viruses lead to an autoimmune response?
Due to mimicy of pathogen and tissue
Give an example of where a virus leads to an autoimmune response
Rheumatic fever with S. Pyogenes
How do viruses cause pathology?
- Direct viral cytopathogenesis
- Viral immunopathogenesis
What do viruses cause in direct viral cytopathogenesis?
- DNA damage
- Alteration of the membrane structure
- Direct cellular cytotoxicity of cellular components
What develops from viral immunopathogenesis?
- Flu-like symptoms
- Delayed hypersensitivity responses
- Immune complex diseases develop
What is the outcome of an infection dependent on?
- The virulence of the infecting pathogen
- Age
- Nutritional status
- General health
- Vaccination history
- Genetic background
- Site of infection
- Number of invading pathogens
By what mechanisms can the pathogen evade the host immune response?
- Polysaccharide capsules to prevent phagocytosis
- Sheltering in protected zones
- Producing enzymes to block chemotaxis
- Blocking of opsonisation
- Mimicry of antigens
Give an example of a protected zone that a pathogen can shelter in?
Abscesses
How can many pathogens persist?
As intacellular pathogens
What must intracellular pathogens evade?
- Phagolysosomal fusion
- Lysosomal enzymes
- Many other mechanisms
What must a pathogen do in order to spread and survive?
Move on to the next host directly, enter the environment, or via a vector
What can a pathogens new environment serve as?
A reservoir for future amplification
