Lecture 24: Micro-organisms in Disease: Infection 2 Flashcards
What is pathogenicity?
The capacity of a micro-organism to cause infection
What are the 4 requirements of pathogenicity?
- Transmissibility
- Establishment in or on a host
- Harmful side effects
- Persistence
What is harm often mediated by?
Harm is often mediated by host response, rather than by the pathogen itself
What is Virulence?
Virulence sometimes defined as the degree to which a micro-organism is able to cause disease.
What does virulence allow relativity of?
Pathogenic potential
What is Infectivity?
The ability of a micro-organism to become established on/in a host
What 2 things is infectivity mediated by?
- Microbial ligand
- Host cell surface receptor
What is virulence factor?
Components of a microorganism which aid its ability to cause infection (infectivity and virulence). Encoded by virulence genes.
What are some examples of a virulence factor?
Facilitation of adhesion
Toxic effect(s)
Tissue-damage
Interference with host defence mechanisms
Facilitation of invasion
Modulation of the host cytokine responses
What are the 6 stages of the cycle of infection?
- Encounter
- Entry
- Spread
- Evade defences
- Multiply and damage
- Disperse
What can impact the speed and severity of the cycle of infection?
The status of the host system
What two types of sources can infection arise from?
- Endogenous sources
- Exogenous sources
What are endogenous sources?
Microorganisms from the host getting into the wrong place
What are exogenous sources?
Organisms originating from the external environment/infected individuals
What does bacterial pneumonia cause?
Infection of the lower respiratory tract– Causes fluid to collect in the alveoli of the lungs
How many people die from pneumonia annually?
4 million
Name 3 organisms that pneumonia can be caused by?
Streptococcus pneumoniae
Staphylococcus aureus
Haemophilus influenzae
What is gonorrhoea?
STI
What organism is gonorrhoea caused by?
Neisseria gonorrhoeae
What rank of commonest STI in the UK does gonorrhoea hold?
2nd
When is peak incidence of gonorrhoea?
Peak incidence 15-19 (women), 20-24 (men)
What are 3 symptoms of gonorrhoea?
– Discharge of pus from urethra
– Burning sensation
– Sterility
Explain the encounter stage of Bacterial pneumonia?
- Inhalation of air-borne droplets containing pathogen
- Contact with mouth of infected individual
- Contaminated blood(?)
Explain the encounter stage of Gonorrhoea?
- Sexual contact with infected individual
- Contact with urethral exudate
- Vertical transmission (mother to child during birth)
What is involved in determining tissue tropism of bacterial infection?
Adhesins
What is the complement system?
– Part of innate immunity
– Enhance phagocytosis(opsonisation)
– Directly kill cells (membrane attack complex)
What is a capsule?
Layer of polysaccharide found on the outside of S. pneumoniae and other pathogens
What is a capsule’s role for a pathogen?
Prevents phagocytosis of pathogen by cells of the immune system
How does the capsule help cause pneumonia?
Allows S. pneumoniae to passthrough mucus
* Prevents complement-mediated killing
What is secretory immunoglobulin A (IgA)
Bind to pathogens and prevent them adhering to host tissues
Where is IgA found?
Found in mucosal secretions of respiratory tract and urogenital tract
What is IgA Protease?
An endopeptidase
Degrades IgA
How does IgA protease degrade IgA?
Targets the amino acid sequence Pro-Pro-Y-Pro (Y=threonine, serine or alanine)
* Hinge region of heavy chain
What can IgA be produced by?
S. pneumoniae and N. gonorrhoeae
What happens to the breakdown of IgA?
Breakdown products of IgA stick to the outside of the pathogen
What is an incubation period?
Period between infection with the organism and manifestation of clinical features
What is the incubation period of chicken pox?
10-21 days
What is the period of infectivity?
Period during which a transmissible organism may be transmitted to another person
What is the period of infectivity of chicken pox?
From 48 hours before the onset of the rash to when all lesions have crusted over
What do pathogens require from the host in order to multiply?
Nutrients
What do pathogen do to the host body? (3)
- Cause direct damage
- Cause indirect damage
- Eliciting a strong immune response
What is pneumolysin secreted by?
Secreted by S. pneumoniae
What happens during the multiply stage of the infection cycle?
Multiple monomers come together (multimerise) and bind to cholesterol in host plasma membrane
– Pore formation
– Host cell releases internal contents (e.g. nutrients) and dies
Which enzyme is capable of degrading Hyaluronic acid and Sialic/neuraminic acid?
Hyaluronidase & Neuraminidase
What are Hyaluronic acid and Sialic/neuraminic acid components of?
Interstitial cement in connective tissue
What does the breakdown of Hyaluronic acid and Sialic/neuraminic acid provide?
Provide nutrients
– Provide more space for organisms to grow
– Activate immune system
What is endotoxin?
A component of the outer-membrane in N. gonorrhoeae
– Isn’t actively secreted (it would be called an exotoxin instead!)
– Released on cell death/lysis
What impact can endotoxin have on the immune system?
Can cause uncontrolled activation of immune response
– Inflammation
– Severe tissue damage
– Multiple organ failure (endotoxic shock, or “sepsis”)
What is the host response to severe sepsis/septic shock?
– T-lymphocyte response
* Cytokine release: e.g. TNF-α, γ-interferon,interleukin-1
* Fever, rigors, hypotension, tachycardia, collapse
* Cardiac and/or renal failure
What does the host response to sepsis activate? (2)
– Activation of the clotting cascade (Disseminated intravascular coagulation (DIC) and Depletion of clotting factors)
– Activation of complement
What are the 5 stages of impact of infection on the host?
- Inflammation
- Abscess formation
- Excessive host response to endotoxin
- Toxic effects of exotoxin
- Granuloma formation
How does the host body defend during inflammation?
Activation of complement and clotting systems, fibrinolysis and kinin system
* Leukocyte adhesion and production of inflammatory mediators
* Local vasodilation
* Reduction in endothelial barrier function
* Increased vascular permeability
* Phagocytosis of foreign material
How does Erythema arise from inflammation?
Vasodilation causes increased blood flow
How does swelling arise from inflammation?
Increased vascular permeability allows extravasation of serum proteins and leukocytes.
Swelling arises from consequent physical and osmotic effects
How does pain arise from inflammation?
Caused by a number of different physical and biochemical changes in inflamed tissue1
How does heat arise from inflammation?
Caused by increased blood flow
How does loss of function arise from inflammation?
Secondary effect of swelling and pain
What is an abscess?
An abscess is an enclosed collection of pus
* Consequence of inflammatory response with phagocytosis of organisms
What does pus consist of?
Pus consists of living and dead white blood cells, exudate, dead tissue and micro-organisms
What are 3 clinical features of abscesses?
The lesion itself (fluid filled fluctuant mass)
* Surrounding inflammation
* Non-specific symptoms of infection (e.g. anorexia, sweats, malaise, fatigue)
What are superficial abscess mainly caused by?
Staph. aureus and Strep. pyogenes
True or false: Any organism may cause a deep (Intraperitoneal) Abscess?
True
What is the impact of exotoxin infection on host?
- Proteins produced (& usually secreted) by living bacteria
- Typically have quite specific effect(s) on host
What is tetanus?
- Infection of dirty wounds
- Toxin production
What toxin is produced from tetanus?
Tetanospasmin
What is tetanospasmin effect on the body?
Produced on germination of spores
– Binds to nerve synapses
– Inhibits release of inhibitory neurotransmitters (e.g.gamma-amino butyric acid) in the central nervous system
How may tetanus cause death?
Can cause respiratory paralysis
Give examples of exotoxin-mediated infections?
Cholera – Vibrio cholerae
* Diphtheria – Corynebacterium diphtheriae
* Clostridium difficile infection – diarrhoea/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
Give the definition of a granuloma?
A focal compact collection of inflammatory cells, mononuclear cells predominating, usually as a result of the persistence of a non-degradable product and of active cell mediated hypersensitivity
Give examples of inflammatory stimuli that causes the formation of Granulomas?
tuberculosis
other mycobacteria
histoplasmosis
cryptococcosis
toxoplasmosis
What type of pathogen is mycobacterium tuberculosis?
Intracellular pathogen
What accounts for the main clinical and radiological features of TB?
Granuloma production
What occurs during primary TB?
Ranke/Ghon complex: solitary granuloma (nodule) with hilar granulomatous lymphadenopathy
What occurs during post-primary/reactivation of TB?
Widespread granulomatous inflammation +/- cavitation, often apical
What occurs during miliary TB?
Multiple disseminated 1-3 mm pulmonary granulomas
What occurs during extrapulmonary TB?
Diverse manifestations in bone, liver, kidneys, CNS etc
What is the infection dose?
Number of organisms required to cause infection
