MCB Lecture 49 Pathogenesis I Flashcards
How may virulence be quantified?
By quantifying the amount of pathogen required to elicit death in the host.
LD50: the dose at which half of the population will die
What do Koch’s postulates describe?
List them
Koch’s postulates describe the requirements to confirm that a bacterium (or microorganism) is responsible for a disease.
- The bacterium must be found in every individual with the disease
- The bacteria must be localised to the lesion
- The bacteria must be able to be cultured outside the host for several generations
- Other organisms must be able to be infected by this culture
- The bacteria must elicit a specific immune response
What is LD50
The dose at which half of the population will die
What is the first stage of infection?
Adhesion to the host epithelial tissue
Compare the distribution of commensals with bacteria that are going to invade a host
Commensals are more loosely associated with host tissue, whereas invading bacteria are closely adhered to the tissue
How do bacteria adhere to the host cells?
Gram negative Bacteria with pilli have specific proteins on the end of their pilli.
These attach to specific oligosaccharides on the outside of the host’s cells.
- Fimbriae
- Non-fimbriae adhesins
Describe how it is possible for certain bacteria to infect specific tissues
The proteins on the outside of cells are tissue specific, that is different tissues have different oligosaccharides.
Thus, certain bacteria will have the correct pilli proteins to bind to the different tissues
Eg. Streptococcus have the correct pilli proteins to adhere to the tissue in the back of the throat
What is the evidence for fimbriae associated adhesion?
- When fimbriae were removed from the bacteria, the infection did not occur
- Hosts can generate antibodies to fimbriae, preventing infection
Immunity may be active or passive
Describe the case of ETEC in piglets
ETEC is a bacterium that causes an infection that causes diarrhoea in piglets.
The bacterium colonise in the gut
The mother pigs are vaccinated by giving them the bacterial fimbriae. The mothers develop antibodies to the fimbriae
The baby piglets receive the antibodies in the milk.
The antibodies kill the bacteria when they get into the gut
Once adhered to the host, what must bacteria do?
Penetrate
How do bacteria get into the epithelial cells
Give an example
Invasins
Eg. Yersinia
Invasins are molecules on the surface of the bacterium that bind to epithelial cells, and bring about endocytosis of the bacterium.
What is are the two mechanisms used by bacteria to survive once inside the body?
- Pyogenic bacteria: Preventing the macrophages or other phagocytes from eating them
- Intracellular parasites: avoid killing once in the phagocyte
Which molecules are released by bacteria to prevent phagocytosis?
Leukocidins
Anti-inflammatory molecules: inflammatory and immune cells are not brought to the site of infection
Explain how capsules prevent phagocytosis
Capsules provide:
- Electrostatic repulsion
- Hide the underlying features
- Resemble host
They can prevent binding of antibodies and thus opsonisation in some cases
What are the three pathways for opsonisation of a bacterium?
- Non-specific: macrophage takes up bacterium at random
- Classical pathway: antibody (IgM) and complement (C3b) binds to the capsule
- Antibody (IgG) and C3b binds to bacterium. Phagocyte expresses FcRecpetor and C3bR
To what do invasions bind, allowing the entry of the bacterium?
Integrins on the host cell
What do pyogenic bacteria do?
They avoid phagocytosis
What is the classification of the diphtheria bacterium?
Gram positive rod
Does bacterial DNA or RNA activate a PRR?
DNA
It is viral RNA that acts as a PAMP
What are the features of Bacillus anthracis?
Gram + rod
Slime layer
Spore forming
What are the features of clostridium tetani?
G+ rod Anaerobic Exotoxin: tetanospasmin Spore forming Vaccine: uses toxin lids Found in soil or gastrointestinal tract
What are the features of E. coli?
G- rod Serotyped with O and H antigen Highly variable genome ETEC: Enterotoxin disrupts permeability of gut -> diarrhoea Fimbriae attachment
What are the features of C. Diphtheriae?
G+ rod
Exotoxin: diphtheria toxin that disrupts host protein synthesis
Vaccine uses toxinoids
Describe the type of vaccine for bacteria that produce exotoxins
Vaccine uses toxinoids
What are the features of staphylococcus aureus?
G+ coccus Common commensal Respiratory infection Food poisoning Exotoxin causes TSS (it's a superantigen)
What are the features of staphylococcus pyrogens?
G+ coccus
Exotoxin is a superantigen producing TSS
What are the features of Klebisiella?
Capsulated
How does the host overcome capsules to prevent infection?
Once encapsulated bacteria are within the body, it is too late. They can’t be phagocytosed unless we have antibodies
Immunity can only be gotten by
- passive immunity: transfusion of capsule antibodies
- active: vaccinate the individual with capsule protein to stimulate the production of capsule antibodies
Which vaccine uses bacterial capsule proteins to give immunity?
Streptococcus pneumoniae
What are the features of Yersinia pestis?
G- rod
Invasin on outer cell membrane that causes pathogen-mediated endocytosis
What are the features of mycobacterium tuberculosis?
Acid fast
Intracellular pathogen: survives inside alveolar macrophages
Bacillus
Hardy
Highly aerobic
PAMP is lipoarabinomannam, unique to its cell wall
What are the features of vibrio cholerae?
G- rod
Exotoxin is cholera toxin
Fimbriae adhesion in the gut
What are the features of streptococcus pneumoniae?
G+ coccus
Encapsulated
Vaccine contains capsule protein
What are the features of salmonella
G- rod
Intracellular pathogen: escapes from the phagosome
Enterobacteria: enters by contaminated food
How do extracellular pathogen evade phagocytosis?
- secrete Leukocidins
- secrete anti-inflammatory toxins and enzymes
- capsules
- secrete pus (pyogenic bacteria)
Give some examples of toxin mediated disease
Staphylococcal food poisoning Staphylococcal toxic shock syndrome Botulism Tetanus Diphtheria
What causes botulism?
Botulinum toxin
It is an exotoxin produced by Clostridium botulinum
What is the manifestation of botulinum?
Paralysis
