11./12. Microorganisms in disease Flashcards
What are the general stages in the chain of infection?
- pathogenic organism
- reservoir
- exit
- transmission
- entry
- susceptible host
What is virulence?
May be used interchangeably to describe pathogenicity
Virulence is sometimes defined as the degree to which a micro-organism is able to cause disease
Staphylococcus aureus and streptococcus viridans are both pathogenic. Which is more virulent?
Staph. aureus is more virulent than strep. viridans, as it causes disease much more readily
Briefly, what are the 4 main Koch’s postulates? (1890)
- organism should be present in disease but not in health
- organism should be isolated from diseased animal and grown in pure culture
- organism should cause the same disease in a newly inoculated animal
- organism should be re-isolated from the experimentally-infected animal
What are the main routes of transmission?
- faecal-oral
- blood-borne
- respiratory
- direct contact (hand-hand, mucous membranes)
What does LD50 mean?
Lethal dose
What does ID50 mean?
Infectious dose
What does infectivity mean?
The ability of a microorganism to become established on/in a host
Infectivity is the ability of a microorganism to become established in/on a host. How can this occur?
- microbial ligand
- host cell surface receptor
Give some examples of ligand-receptor interactions
- E. coli P fimbriae: glycolipids on human uroepithelial cells (tiny hair-like structures that express specific adhesins)
- S. pyogenes protein-F: fibronectin1 (large multifunctional glycoprotein found in connective tissue, on cell surfaces, and in various body fluids)
- influenza haemagglutinin: respiratory epithelial sialic acid receptors
What are virulence factors?
Components of microorganisms that result in harmful effects
Give some examples of virulence mechanisms
- facilitation of adhesion
- toxic effect(s)
- tissue damage
- interference with host defence mechanisms
- facilitation of invasion
- modulation of the host cytokine responses
What are virulence factors sometimes referred to as?
- adhesins
- aggressins
- interferins
- modulins
etc
An endotoxin is a type of what?
Virulence factor
Are endotoxins release from the live or dead bacterial cell?
Endotoxins are released from damaged/dead cells
Where are endotoxins found?
They are a component of the gram-negative bacterial cell wall
- E.coli and other gram-negative bacilli
- Neisseria meningitidis
Which class of bacteria possess endotoxins?
Gram-negative bacteria
What is the active component of endotoxins?
Lipopolysaccharide (LPS)
the term LPS often used interchangeably with endotoxin
What do endotoxins do?
Binds to a number of host cell receptors
Induces a range of uncontrolled host responses
Strictly speaking, what is a lipopolysaccharide?
Any polysaccharide containing lipid
A host response to an endotoxin is SIRS - systemic inflammatory response syndrome. What is involved in this?
- uncontrolled T-lymphocyte response
- uncontrolled activation of the clotting cascade
- uncontrolled activation of complement
One of the components of SIRS is uncontrolled T-lymphocyte response. What is involved in this?
- cytokine release: TNF-a, y-interferon, interleukin-1
- fever, rigors, hypotension, tachycardia, collapse
- cardiac and/or renal failure
One of the components of SIRS is uncontrolled activation of the clotting cascade. What is involved in this?
- disseminated intravascular coagulation (DIC)
- depletion of clotting factors
- bleeding tendency
SIRS (systemic inflammatory response syndrome) encompasses imprecise terms such as what?
Septic shock and endotoxic shock
What is Waterhouse-Friedrichsen syndrome?
An example of the catastrophic effects of endotoxin
Meningococcal infection results in bilateral adrenal haemorrhage and subsequent adrenal failure, largely due to endotoxin release from Neisseria meningitidis
Give a consequence of Neisseria meningitidis infection?
Endotoxin-mediated increase in vascular permeability causes loss of protein, fluid and plasma into the tissues, with pathological compensatory vasoconstriction
Exotoxins are types of what?
Virulence factors
What are exotoxins? What are they produced by?
Proteins produced by living bacteria
Do exotoxins have broad or specific effects?
Exotoxins usually have quite specific effect(s) on the host
What is botulism caused by?
Exotoxins produced by clostridium botulinum (obligate anaerobe)
The toxins block the nerve impulse from getting to the muscles at the neuromuscular junction
How is botulism caused?
- ingestion of pre-formed toxin (contaminated food)
- infection of dirty wounds (may be trivial wounds)
- gastrointestinal colonisation (infants)
What are the general symptoms of botulism?
- double vision
- drooping eyelids
- sore throat
- flaccid paralysis
- respiratory failure
What is the clinical presentation of botulism (in medical terms)? Hint:5 Ds
- diplopia
- dysphagia
- dysarthria
- dry mouth
- death (from respiratory failure)
At which sites do botulism toxins act?
At the neuromuscular junction
What causes tetanus?
The toxin released by clostridium tetani (obligate anaerobe)
How is tetanus caused?
- infection of dirty wounds (may be trivial wounds)
- toxin production
- death caused by respiratory paralysis
What is the tetanus toxin caused?
Tetanospasmin
What are the effects of tetanospasmin (the tetanus toxin)?
- produced on germination of spores
- binds to nerve synapses
- inhibits release of inhibitory neurotransmitters (eg. gamma-amino butyric acid) in the central nervous system
Ultimately, how is death caused in tetanus?
Death is caused by respiratory paralysis
What does obligate anaerobe mean?
Means they are poisoned by oxygen
What are the main symptoms of tetanus?
- jaw stiffness (lockjaw)
- muscle spasms
- fever
- sweating
- tachycardia
Developing into muscle rigidity and respiratory failure
As well as botulism and tetanus, give some other exotoxin-mediated infections
- cholera (vibrio cholerae)
- diphtheria (corynebacterium diphtheriae)
- clostridium difficile infection (causing diarrhoea and colitis)
- E. coli O157 haemorrhagic colitis (verotoxin)
- staphylococcal scalded skin syndrome (Staph. aureus)
- whooping cough/pertussis (bordetella pertussis)
- scarlet fever (strep. pyogenes)
- scalded-skin syndrome (staph. aureus epidermolysin)
What do streptococcus pyogenes virulence factors do?
They promote connective tissue breakdown and invasion
Give some streptococcus pyogenes syndromes
- streptococcal sore throat
- erysipelas
- necrotising fasciitis
- scarlet fever
What are the streptococcus pyogenes virulence factors?
- hyaluronidase and streptokinase
- C5a peptidase
- streptolysins -O and -H
- erythrogenic toxin (phage-encoded)
- toxic shock syndrome toxin
Hyaluronidase and streptokinase are virulence factors of S. pyogenes. What do they do?
Break down connective tissue components - facilitate tissue invasion
C5a peptidase is a virulence factor of S. pyogenes. What does it do?
Inactivates complement component C5a
Streptolysins -O and -H are virulence factors of S. pyogenes. What do they do?
Lyse red and white blood cells and platelets
Erythrogenic toxin (phage-encoded) is a virulence factor of S. pyogenes. What does it do?
Causes the rash of scarlet fever
Toxic shock syndrome toxin is a virulence factor of S. pyogenes. What does it do?
Streptococcal toxic shock syndrome is superficially similar to a syndrome of endotoxin release
What is responsible for the rash in scarlet fever?
The erythrogenic toxin (phage-encoded) produced by S. pyogenes
In what ways do pathogens evade the immune system?
- inhibition of phagocytosis
- intracellular pathogens
How does S. pyogenes inhibit phagocytosis?
M-protein binds fibrinogen and masks bacterial surface, blocking complement binding and opsonisation
How does S. pneumoniae inhibit phagocytosis?
Polysaccharide capsule inhibits opsonisation and therefore phagocytosis
Give some intracellular pathogens (helps immune evasion)
- myobacterium tuberculosis
- salmonella typhi
- listeria monocytogenes
What are the 2/3 components that viruses consist of?
- genome (RNA or DNA)
- capsid (protein)
- (envelope - lipid bilayer)
Viruses are incapable of what?
Independent existence
What do viruses use to satisfy the requirements of growth and replication?
Host mechanisms
What are the stages in the generic virus life cycle?
- adsorption
- penetration
- uncoating
- synthesis
- assembly
- release
Adsorption is the first stage in the virus life cycle. What is this?
Interaction between host receptor molecule and virus ligand (determines host-specificity of the virus)
Penetration is the second stage in the virus life cycle. What is this?
Receptor-mediated endocytosis or, in some enveloped viruses, membrane fusion
Uncoating is the third stage in the virus life cycle. What is this?
Nucleic acid is liberated from the phagosome (if endocytosed) and/or capsid by complex enzymatic and/or receptor-mediated processes
Synthesis is the fourth stage in the virus life cycle. What is this?
Nucleic acid and protein synthesis are mediated by host and/or viral enzymes. These take place in nucleus or cytoplasm, depending on the specific virus
Assembly is the fifth stage in the virus life cycle. What is this?
Assembly of virus components is mediated by host and/or viral enzymes
Release is the sixth stage in the virus life cycle. What is this?
Complete virus particles are released by budding off host cell membrane or disintegration of host cell
What is endocytosis?
A form of active transport in which a cell transports molecules into the cell by engulfing them in an energy-using process
