Infection Flashcards
What is the definition of pathogenicity?
the capacity of a micro-organism to cause infection
What are the 4 requirements of an organism to have pathogenicity?
- transmissibility (ability of an organism to be transmitted from one individual from another) 2. establishment in or on a host 3. harmful effects 4. persistence
What is meant by persistence of a micro-organism?
the ability to subvert the immune system in some manner so it can persist for long enough to survive, reproduce and be transferred to another individual
What is the definition of virulence?
the degree to which a micro-organism is able to cause disease a more virulent organism will cause disease more readily
What is the definition of infectivity?
the ability of a micro-organism to become established on/in a host
What factors are involved in mediating infectivity?
- microbial ligand 2. host cell surface receptor
What is the definition of a virulence factor?
components of a micro-organism which aid its ability to cause infection encoded by virulence genes
What are examples of the actions of virulence factors?
- facilitation of adhesion 2. toxic effects 3. tissue-damage 4. interference with host defence mechanisms 5. facilitation of invasion 6. modulation of the host cytokine response
What are the 6 stages in the cycle of infection?
- encounter
- entry
- spread
- evade defences
- multiply and damage
- disperse
What factors can influence the cycle of infection?
the status of the host immune system can impact the speed and severity of the cycle
What is the difference between an endogenous and exogenous source of infection
Endogenous:
microorganisms already in the host body travel into a priviledge site (somewhere where they shouldn’t be)
Exogenous:
organisms originate from the external environment
What is bacterial pneumonia?
it is an infection of the lower respiratory tract that causes fluid to collect in the alveoli
this impairs gas exchange and leads to poor oxygen uptake
Which groups of people are more susceptible to bacterial pneumonia?
- extremes of age (old and young)
- immunocompromised individuals
What are the 3 main microorganisms which can cause bacterial pneumonia?
- streptococcus pneumoniae
- staphylococcus aureus
- haemophilus influenzae
What is gonorrhoea and what organism causes it?
What age group is most commonly affected?
it is an STI caused by Neisseria gonorrhoeae
peak incidence is 15-19 in women and 20-24 in men
What are the main symptoms of gonorrhoea?
- discharge of pus from the urethra
- burning sensation
- sterility
What is meant by gonorrhoea having a sex bias to symptoms?
90% of infected men show symptoms, but only 20% of infected women show symptoms
What is involved in the encounter stage when looking at bacterial pneumonia?
- inhalation of air-bourne droplets containing the pathogen
- contact with mouth of infected individual
- contaminated blood
What is involved in the encounter stage when looking at gonorrhoea?
- sexual contact with an infected individual
- contact with urethral exudate
- vertical transmission
What aids in the entry/colonisation of N. gonorrhoeae?
pilli facilitate attachment of the diplococci to the walls of the urogenital tract
What is a common molecule that many microorganisms adhere to?
What does this mean?
fibronectin
this is a common receptor on the surface of many cells meaning that the organism can cause infection in multiple parts of the body
What is the adhesin and receptor of N. gonorrhoeae?
adhesin - fimbriae
receptor - GD1 ganglioside
GD1 ganglioside is also found in the respiratory tract so it is possible to get gonorrhoea of the RT
What are the 2 different methods of entry of a microorganism?
Ingress:
organism gains access through a standard site that is open to the external environment
Penetration:
the breakthrough and introduction of the organism into a priviledge site e.g. through a scratch
What are the main components of a microorganism involved in spreading and evading defences?
- flagella
- capsule
- IgA protease
- pneumococcal surface protein A
What is a capsule?
How can it aid a pathogen in surviving (3 main ways)?
it is a layer of polysaccharide found on the outside of pathogens
it prevents phagocytosis of pathogens by the cells of the immune system
it allows S. pneumoniae to pass through mucus
it prevents complement-mediated killing
What is the role of pneumococcal surface protein A?
it prevents complement mediated killing
What are the 2 main roles of the complement system?
- it enhances phagocytosis through opsonisation
- it directly kills cells through the membrane-attack-complex
How does pneumococcal surface protein A interact with antibodies?
It can bind to the Fc region of antibodies so that they are facing the wrong way
This prevents them from using their antigen binding site
Where is secretory IgA found and what is its role?
found in mucosal secretions of the respiratory tract and urogenital tract
it binds to pathogens to prevent them from adhering to host tissues
What type of compound is IgA protease?
What is its role?
it is an endopeptidase
it degrades IgA
What is an endopeptidase?
it targets amino acid chains in the middle of the protein, opposed to at the terminal ends
What part of IgA is targeted by IgA protease?
the amino acid sequence Pro-Pro-Y-Pro
Y = threonine, serine or alanine
this is found on the hinge region of the heavy chain
How can IgA protease help S. pneumoniae and N. gonorrhoeae evade the immune system?
the breakdown products of IgA stick to the outside of the pathogen
this allows it to evade the immune system
Label the components of secretory IgA
What is meant by the ‘incubation period’?
the period between infection with the organism and the manifestation of clinical features
What is meant by the ‘period of infectivity’?
period during which a transmissable organism may be transmitted to another person
this can happen BEFORE the patient shows the clinical features of the disease
What is required for a microorganism to multiply?
How may they elicit damage in the process?
they need to acquire nutrients from the host to multiply
they may cause direct or indirect damage to the host in order to do this
What is the most common way in which a pathogen will cause indirect damage to a host?
by stimulating the host to damage itself through the production of a strong and unnecessary immune response
What organism produces pneumolysin?
S. pneumoniae
What are the stages involved in pore formation by pneumolysin?
- soluble monomer secreted by S. pneumoniae
- multiple monomers come together and multimerise and bind to cholesterol in the host plasma membrane
- this produces the prepore
- a change in structure forms a pore which punches a hole in the host cell membrane
How does pneumolysin cause damage to the host cell?
The pore causes the host to release internal contents into the external environment
the host cell dies and nutrients are released for the pathogen
What are the roles of hyaluronidase and neuraminidase?
they are enzymes which degrade hyaluronic acid and neuraminic acid
these are components of interstitial cement in connective tissue (hyaluronic) or epithelial cells (neuraminic)
What can the breakdown of hyaluronic acid/neuraminic acid achieve for the pathogen?
- provision of nutrients
- activation of the immune system
- provision of more space for the pathogen to grow
What component of a gram-negative bacterial cell envelope is responsible for endotoxic shock?
lipopolysaccharide
What is an endotoxin?
a lipopolysaccharide that is released on cell death/lysis
it is NOT actively secreted
What does the release of an endotoxin usually cause in the host cell?
uncontrolled activation of the immune response, leading to:
- inflammation
- severe tissue damage
- multiple organ failure (endotoxic shock/sepsis)
What are the rough stages that are involved with the host response to an endotoxin?
T-lymphocyte response:
cytokine release leads to fever, rigors, hypotension, tachycardia and collapse
Activation of the clotting cascade:
leads to disseminated intravascular coagulation and depletion of clotting factors
Activation of complement
What is the end result of endotoxic shock and what is it brought about by?
Initially, warm shock involves the induction of systemic vasodilation and leaky capillaries
There is a period of hypotension
The body then employs compensatory vasoconstriction
This eventually leads to shock, organ dysfunction and DIC
What is an example of a host response to an endotoxin released by N. meningitidis?
- endotoxin-mediated increase in vascular permeability causes loss of protein, fluid and plasma into the tissues
- there is pathological compensatory vasoconstriction
- this leads to necrosis of the extremities, which requires amputation
Which systems are activated in inflammation?
- complement
- clotting
- fibrinolysis
- kinin
What is the result of leukocyte adhesion and production of inflammatory mediators in inflammation?
- local vasodilation
- reduction in endothelial barrier function
- these lead to increased vascular permeability
What is the result of erythema in host inflammation?
vasodilation causes increased blood flow
this allows increased amounts of immune system components to reach the site of infection
What causes swelling in host inflammation?
increased vascular permeability allows extravasation of serum proteins and leukocytes
What causes pain, heat and loss of function in host inflammation?
pain is caused by different physical and biochemical changes in the inflamed tissue
heat is caused by increased blood flow
loss of function is a secondary effect of swelling and pain
What are the 4 Streptococcus pyogenes syndromes?
- erysipelas
- streptococcal sore throat
- scarlet fever
- necrotizing fascitis
How is S. pyogenes often recognised on a petri dish?
when placed on blood, it is capable of producing toxins that cause beta-haemolyisis
What is the role of hyaluronidase and streptokinase as a S. pyogenes virulence factor?
they break down connective tissue components, facilitating tissue invasion
What is the role of the toxic shock syndrome toxin as an S. pyogenes virulence factor?
it is a superantigen
it binds to the outside of the MHC class II molecule
this makes it non-specific so that it activates every T-cell within the region
this leads to a strong immune response which can be pathological in itself
What is the role of the erythrogenic toxin as an S. pyogenes virulence factor?
it causes the rash of scarlet fever
What is the role of C5a peptidase as an S. pyogenes virulence factor?
it inactivates complement component C5a
What are the roles of streptolysins -O and -H as S. pyogenes virulence factors?
they are involved with lysis of red and white blood cells and platelets
What is an abscess?
an enclosed collection of pus
it is a consequence of localised or systemic inflammation with phagocytosis of organisms
What does pus consist of?
- living and dead white blood cells
- exudate
- dead tissue
- microorganisms
What are the main clinical manifestations of an abscess?
- the lesion itself - a fluid-filled fluctuant mass
- surrounding inflammation
- non-specific signs of infection - e.g. anorexia, sweats, malaise, fatigue
What are the main organisms which cause a superficial abscess?
- Staphylococcus aureus*
- Streptococcus pyogenes*
These are pyogenic organisms
What are the 2 types of abscesses?
superficial or deep
What is the role of the fibrous capsule in abscess formation?
What can interrupt this process?
it acts to try and stop the infection from spreading to other sites
organisms can express proteolytic enzymes which can break down the fibrous capsule, allowing them to cause a systemic infection
What is the difference between a B and an A component of an exotoxin?
B - binding component:
this allows the toxin to bind to a receptor and be endocytosed
A - active component:
this is the part which causes damage to the host cell
The B component facilitates entry of the A component into the host cell
How does the botulinum toxin affect the body?
it prevents the release of ACh at nerve synapses
this means there is no muscle contraction
it leads to flaccid paralysis and respiratory failure
How is wound botulism treated?
with penicillin and botulinum antitoxin
ventilation in ICU is needed for the respiratory failure
How does Clostridium tetani (tetanus toxin) affect the body?
it caauses muscle rigidity and respiratory failure
patients often complain of jaw spasms
What is the treatment for tetanus infection?
metronidazole and tetanus antitoxin
ventilation in ICU is needed for respiratory failure
What is significant about the effects of exotoxins on the host?
they tend to have very specific effects on the host body
How does someone usually contract an infection with Clostridium tetani?
through infection of dirty wounds
What is the tetanus toxin called?
How does it affect the body?
tetanospasmin
it binds to nerve synapses and inhibits the release of inhibitory neurotransmitters (e.g. GABA)
this leads to severe muscle contraction and death by respiratory paralysis
What is a granuloma?
Why does it occur?
it is a compact collection of inflammatory cells and mononuclear cells as a result of the persistence of a non-degradable product and of active cell-mediated hypersensitivity
it is the body’s response to an organism that cannot be broken down and killed
What infectious agents tend to cause a granuloma?
- tuberculosis
- other mycobacteria as the mycolic acid layer prevents breakdown
- histoplasmosis
- cryptococcosis
- toxoplasmosis
What are the radiological and clinical manifestations of a granuloma?
radiological - a nodule is present
clinical - tissue necrosis
What accounts for the main clinical and radiological features of tuberculosis?
granuloma production
how is primary tuberculosis identified?
By the Ranke/Ghon complex
this is a solitary granuloma (nodule) with hilar granulomatous lymphadenopathy
How is post-primary/reactivation TB identified?
through widespread granulomatous inflammation +/- cavitation
this is often apical
How are miliary and extrapulmonary TBs identified?
MIliary - multiple disseminated 1-3mm pulmonary granulomas
Extrapulmonary - diverse manifestations in bone, liver, kidneys, etc.
Why are immunocompromised patients more susceptible to Mycobacterium tuberculosis infection?
granuloma formation is an active process
if the immune system is impaired, the granuloma cannot be maintained
the organisms escape from the granuloma and disseminate
What factor promotes dispersal of a pathogen?
damage to the host cells
What influences dispersal in pneumonia?
inflammation of lung tissue leads to production of fluid containing the pathogen
this induces coughing
this leads to dispersal of the pathogen through respiratory droplets
How can damage to the host influence dispersal of gonorrhoea?
damage to tissues of the genital tract induces an immune response
this leads to production of urethral discharge
this leads to dispersal via sexual contact
What is meant by the ‘infectious dose’?
the minimum number of organisms required in order to cause an infection
