Immunology and Microbiology Flashcards
What kinds of local host factors predispose an individual to opportunistic infections?
Anatomical defects
- example: short urethra in females leading to UTIs
Surgical and other open wounds
Burns
Catheterisation (bladder or IV)
Foreign bodies in the body
- example: sutures that contain foreign material provides an environment supportive of opportunistic growth
What kinds of systemic host factors can predisposes an individual to opportunistic infection?
Extremes of Age (via loss of immune function)
Leucopenia
Malignancy
Malnutrition
Diabetes
Liver Disease
Certain infections (i.e immunocompromising HIV infection)
Treatment with antimicrobials (i.e antibiotics to clostridium difficile or altering protective microflora)
Primary immunodeficiencies
Are endogenous or exogenous microbes the most common source of opportunistic infections?
Opportunistic infections are most commonly the result of engoenous /self microbiota
What does the term nosocomial refer to?
Are nosocomial infections more difficult to treat?
Nosocomial refers to microbes and infections typically aquired in an institutional setting.
Institutions include hospitals, aged care facilities etc.
Nosocomial microbe strains are often multiresistant to drug treatments -> are more difficult to treat
Describe the Pseudomonas family of bateria
Pseudomonas are gram negative rods
- Aerobes or facultative anaerobes
- Motile - posses flagelli for movement
- Some species produce pigments -> pyocyan pigment = turquoise/green pus with a foul odour
- Non-fermenting and non-sporing
- Catalase and oxidase positive
- Wide-spread
- Low nutritional requirements
What is the most common and medically significant species of Pseudomonas?
How can this species be subtyped?
Pseudomonas Aeruginosa
Pseudomonas Aeruginosa is further classified according to serotype and seldomly biotype. In epidemiological studies; the species is subtyped into strains via multilocus sequence typing (MLST)
What is the medical significance of Burkholderia Pseudomallei
Burkholderia Pseudomallei is a from a related genera to Pseudomonas.
It causes meliodosis
The symptoms of melioidosis depend on the site of the infection and this can vary. Often it starts as a chest infection with shortness of breath, productive cough and fever
It is a particularly prevalent cause of pneumonia in the Northern Territiory
List three opportunistic pathogens that commonly infect patients with cystic fibrosis
Pseudomonas Aeruginosa
Burkholderia Capacia
Stenotrophomonas Pseudomallei
Describe the epidemiology of Ps. Aeruginosa
Is an environmental microbe widespread throughout nature - especially moist environments
Transient coloniser of skin, mucous membranes and GIT
Is an opportunistic pathogen - particularly in cystic fibrosis patients
An important nosocomial pathogen:
- Traditionally associated with burns and febrile neutropenia
- Currently associated with pneumonia, UTI and sepsis
Aquired from environment and spread on hands and fomites
- Some strains can spread between cystic fibrosis patients
Discuss the resistance associated with Ps. Aeruginosa
All strains of Ps. Aeruginosa are intrinsically resistant to many antibiotics and weak disinfectants
Resistance is also readily aquired from other bacterial via horizontal gene transfer
What diseases are caused by Ps. Aeruginosa?
Superficial Infections:
Skin: wound infections, otitis externa and folliculitis (infection of hair follicules)
Eye: keratinitis, corneal ulcer
Deep or Systemic Infections
Pulmonary: Nosocomial pneumonia, chronic infection in CF patients
Other: UTI, endocarditis, osteomyelitis and septicaemia (immunocompromised patients)
Describe the pathophysiology of Ps. Aeruginosa
- Adheres weakly to intact epithelium via flagella, pili and LPS
- LPS and flagellin bind toll-like receptors; this also upregulates immune system cytokine production
- LPS core binds to CFTR
- In normal people, binding pseudomonas to CFTR is protective -> holds bacteria for macrophages to detroy it. This process is lost in cystic fibrosis patients who have a mutated CFTR gene/protein.
- Once adherent, bacteria produce biofilm
* Ps. Aeruginosa capsule assists adherence and the formation of biofilm.
NOTE: Invasion only occurs in very large numbers
How do the properties of Ps. Aeruginosa change when in biofilm?
Ps. Aeruginosa undergo changes in gene expression when in biofilm. This is a result of quorum sensing.
- Non-motile
- More capsule material / mucoid phenotype
- More adherent
- Less invasive
- Shorter LPS (no O-antigen)
- Slowed growth
- Increased resistance to antibiotics
What factors contribute to the elevated spread of Ps. Aeruginosa
- Reduced PMN / Febrile Neutropenia
- Flagella - more motile
- Production of Exoenzymes: proteases. haemolysins, elastases and phospholipases
- Exotoxins: exotoxin A, exotoxin S and exotoxin U inhibit phagocytosis
- LPS-CFTR mediated invasion - particularly into the cornea
What happens in patients with Cystic Fibrosis?
CF patients have a defect in CFTR which leads to abnormal ion transport, thickened mucus and impaired mucocilliary function
Ps. Aeruginosa and Staph are not inhibited by high salt concentrations
The biofilm state of Ps. Aeruginosa confers resistance to mechanical removal and are less visible to the innate immune system
DNA secreted by bacteria and released from dying cells thicken the mucus further
The bacterial variant that persist are the Pseudomonas bacteria in the biofilm form (the less virulent form)
How is Ps. Aeruginosa controlled?
Ps. Aeruginosa cannot be eradicated from the environment; management must be directed towards preventing infections in the first instance:
- Practice high levels of hand hygiene
- Reduce the risk of susceptible patients to exposure by suitable management of burns, neutropenia, catheters etc.
- Be alert for infections and treat early
- Use contact lenses appropriately
- Life long monitoring and treatment of CF patients
What is the definiion of pyrexia of unknown origin (PUO)?
- Prolonged illness (2-3 weeks duration)
- Fever (>38.3 degrees) on several occasions
- No diagnosis after intelligent investigations
Discuss the homeostasis and normal values of body temperature
Body temperature is kept within a narrow homeostatic range to ensure optimal conditions for metabolic and neuronal activity is maintained.
The average oral temperature range is 35.8-37.8
Body temperature varies in a diurnal pattern -lower in morning and higher in the afternoon (0.5-1.0 variation)
Body temperature is regulated in the anterior hypothalamus by temperature sensitive neurons -> controls the balance between heat loss and production:
- Heat loss via peripheral vasodilation, sweating and reduced physical activity
- Heat conservation via peripheral vasoconstriction, piloerection abd warmth seeking behaviour
- Heat generated through shivering and the release of thyroid hormones, glucocorticoid and/or catecholamines
At what temperature is a fever deemed to occur?
A fever is characterised by:
- Early morning oral temperature > 37.2
- Oral temperature >37.8 any time of the day
There is a margin of error with methods of measuring internal blood pressure as it is difficult to obtain a direct measure:
- Oral temperature < core body temp by 0.5
- Axillary temp < core body temp by 1.0
- Ear probe temp closer to core temp.
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Describe the processes involved in a febrile response
Why do we have a febrile response?
A febrile response or fever is a mechanism in which the body regulates the immune system to an infective challenge
A rise in core temperature “switches on” a range of immune, endocrine and physiologically mechanism around their optimum activity levels of 39.5 degrees
BUT… it is expensive, in terms of energy, to maintain such a level of metabolic activity to keep temperature at a febrile level,
View attached image outlining the processes leading to fever formation.
