Microbiology Flashcards
Describe the aspergillilus fungus.
Describe the cryptococcus neoformans fungus.
Describe the Candida albicans fungus.
Spores disperse in air and go to lung
Can form aspergilloma (clump of mould) in organ which can cause haemorrhage
Cryptococcus neoformans - branched yeast
Can form multiple cryptococcomas in the brain
Usually in HIV patients which can cause meningitis (white lumps)
Candida albicans
Yeast, mucosal infections
Candida endophthalmitis - intraocular infection, bloodstream infection
Describe cellular immunity to fungal infection.
- opsonisation by pentraxin 3 and mannose-binding lectin
- phagocytes are a critical first line of defence
- NK cells provide early interferon-gamma
- A failure of innate immunity leads to adaptive responses
- dendritic cells influence T cell differentiation
- Th1 and Th17 play a role
Describe fungal morphogenesis, virulence and immunity.
Candidates dimorphism (yeast/hyphae forms) allows tissue invasion
Cryptococcus forms a capsule to evade phagocytosis
Aspergillus species inhaled as conidia, invade tissues as hyphae
(Side note: toll is an innate pattern recognition receptor in Drosophilia (flies) required for fungal immunity)
What are human immune deficiencies that lead to fungal infections.
Human Dectin 1 deficiency
- leads to mucocutaneous fungal infections
- Dectin 1 is a major fungal pattern recognition receptor
- Thrush like infection = CMC (chronic mucocutaneous candidiasis)
- There is impaired macrophage interleukin-6 production in response to C. Albicans and impaired macrophage binding of Candida albicans
Human CARD9 deficiency
- CARD9 deficiency leads to CMC
- functional CARD9 is required for TNFalpha production in response to Beta-glucan stimulation
- functional CARD9 is required for T cell Th17 differentiation
TLR4 polymorphisms
-increase risk of invasive Aspergillosis in transplantation
-TLR4 S4 loss or function mutation leads to this increased risk
-dectin 1 mutations also increase risk and so so do plasminogen alleles
-viral mutations in Dectin-1, TLR4 and plasminogen confer increased
susceptibility to fungal disease
Describe the role of the innate and adaptive responses in fungal infections.
Neutrophil nets - good at killing hyphae (DNA traps)
• These chromatin molecules outside the nucleus act as “danger signals” and recruits effector cells to the area as well.
Fungal morphogenesis – fungi can transition between yeast, candida and hyphae forms (multicellular) and this can drive a modulation of Dendritic cell response and can be bad for the immune response (as it gets confused).
Innate defences:
o Mucosal immunity governs fungal tolerance and resistance.
Treatment:
o Adoptive immunotherapy – generate lots of antifungal T-cells in a sample and then give these to the patients that need to fight a fungal infection.
o Gene therapy – e.g. restore gp91 function (make reactive oxidative species to fight fungal spores) to treat chronic granulomatous disorder. E.g. restore neutrophil NET formation.
• Both macrophages and neutrophils contribute to fungal immunity
• However for Aspergillus neutrophils are of primary importance
• Dendritic cells modulate adaptive immune responses
• Adaptive T cell interferon-gamma responses augment host immunity
to fungi
• Interferon-gamma or adoptive T cell therapy have emerging utility for
the treatment of fungal infections
• Gene therapy for primary immunodeficiencies
Describe fungal allergy.
Many fungal spores are inhaled daily.
Host response may be normal, ineffective or exaggerated (allergy).
o This leads to either an allergic or invasive fungal disease.
Aspergillus is a primary driver – other fungi may contribute.
o Aspergilli – Aspergillus niger, Aspergillus fumigatus.
o Other supporting fungi – Alternaria, Cladosporium, Penicillum.
Important fungal reactions include type 1, 3, 4 hypersensitivity reactions.
o T1 – IgE-driven, involves histamine and leukotrienes, in minutes.
o T2 – IgG-, IgM-driven, involves complement, in 1-24 hours.
o T3 – IgG-, IgM-driven, involves complement, in 1-24 hours.
o T4 – T-cell-driven, involves lymphokines, in 2-3 days.
Describe allergic bronchopulmonary aspergillosis.
Pathophysiology
Abnormality in dendritic cells
Abbarent Th2/17 —> class switching IgE rather than IgG —> mass cell granulation
Criteria for allergic bronchopulmonary aspergillosis
Predisposing conditions
• Asthma or cystic fibrosis
Obligatory criteria
• Total baseline serum IgE >1000 IU/ml
• Positive immediate hypersensitivity skin test or Aspergillus-specific IgE
Supportive criteria (more than 2 present)
• Eosinophilia >500cells/ul
• Serum precipitating or IgG antibodies to Aspergillus fumigatus
• Consistent radiographic abnormalities
Radiological features of ABPA • Dilated bronchi with thick walls • Ring or linear opacities • Upper or central region predeliction • Proximal bronchiectasis • Lobar collapse due to mucous impaction • Fibrotic scarring Airway obstruction may cause mild asthma
Management
- Corticosteroids
- Itraconazole for steroid sparing effect
- Benefit of itraconazole past 16 weeks unclear
- Reduction in circulating IgE, (anti IgE) steroid dependency and improved PFT
- Itraconazole indicated if not responding to steroids or steroid-dependent
- Role of inhaled steroids and other antifungals less clear
- Recombinant IgE monoclonal antibodies (omalizumab) may be useful
Describe aspergillus rhinosinusitis.
• May be allergic or invasive
• Increasingly common
• Association with atopy and nasal polyposis
• Raised total IgE, skin test and Aspergillus-specific RAST IgE (or sometimes IgG)
• May also be caused by Bipolaris or Curvularia
• Obliterated sinuses with hypo attenuated
mucosa and enhancing material on imaging
Treatment
• Oral corticosteroids
• Surgical removal of obstructing nasal tissue
• Systemic anti-fungal treatment has not been shown to be
effective
• Topical therapies being investigated
Describe severe asthma with fungal sensitisation.
• Severe asthma
• Positive immediate skin test or in vitro specific IgE to >1
filamentous fungus
• Exclusion of allergic bronchopulmonary aspergillosis
• Controversial diagnosis due to concerns about
generalised sensitization
• Use of antifungals unclear
Histamine, house dust mite etc.
Describe hypersensitivity pneumonitis.
- Also known as extrinsic allergic alveolitis
- Allergic response requiring long-term allergen exposure
- As a consequence often occupational
- Cell-mediated delayed sensitivity reaction
- Allergen-specific precipitins usually present
(Diagnosis for different pulmonary allergies - ABPA, aspergillus rhinosinusitis, severe asthma with fungal sensitisation, hypersensitivity pneumonitis) to fungi can be driven by skin test, IgE and IgM)
List important bacterial virulence factors.
-Diverse secretion systems
-Flagella (movement, attachment)
-Pili (important adherence factors)
-Capsule (protect against phagocytosis)
i.e. Streptococcus pneumoniae
-Endospores (metabolically dormant forms of bacteria)
heat, cold, desiccation and chemical resistant
i.e. Bacillus sp. and Clostridium sp.
-Biofilms (organized aggregates of bacteria embedded in polysaccharide matrix – antibiotic resistant)
i. e. Pseudomonas aeruginosa
i.e. Staphylococcus epidermidis
EXOTOXINS
- Neurotoxins (act on nerves or motor endplate) i.e. Tetanus or Botulinum toxins
- Enterotoxins (act on the GI tract)
1) Infectious diarrhea i.e. Vibrio cholera, Escherichia coli, Shigella dysenteriae and Campylobacter jejuni
2) Food poisoning i.e. Bacillus cereus or Staphylcoccus aureus i.e. Staphylcoccus aureus or Streptococcus pyogenes - Pyrogenic exotoxins (stimulate release of cytokines)
- Tissue invasive exotoxin (allow bacteria to destroy and tunnel through tissue) enzymes that destroy DNA, collagin, fibrin, NAD, red or white blood cells
i. e. Staphylococcus aureus, Streptococcus pyogenes Clostridium perfringens - Miscellaneous exotoxin (specific to a certain bacterium and/or function not well understood)
i. e. Bacillus anthracis and Corynebacterium diphtheriae
ENDOTOXINS
• Only produced by Gram-negative bacteria
• Not a protein but the lipid A moiety of LPS
• Shed in steady amounts from living bacteria
• Treating a patient who has a Gram-negative infection with antibiotics can sometimes
worsen condition → when bacteria lyse they release large quantities of LPS/ Endotoxin —> Septic shock
Define an outbreak of infectious disease and how they are identified.
An outbreak is a greater-than-normal or greater-than-expected number of individuals infected or diagnosed with a particular infection in a given period of time or a particular place or both.
It is identified by surveillance systems which provide an opportunity to identify outbreaks
Good and timely reporting systems are instrumental to identify outbreaks
Describe bacterial pathogens that cause community’s acquired infections in Europe.
E-coli outbreak - caused by a Shiga-toxin producing E-colo
Lead to gastroenteritis and haemolytic-uremic-syndrome
Haemolytic-uremic syndrome
- triad of acute renal failure, haemolytic anaemia and thrombocytopenia
- human infection occurs through ingestion of faecal matter and secondary through contact with infected humans
- usually in children, rare in adults
- Caused by EHEC – enterohaemorrhagic E. coli.
The outbreak was the result of a fusion the EHEC and the EAHC strains to form the EAHEC strain.
o EHEC – Enterohaemorrhagic E. coli.
o EAEC – Enteroaggregative E. coli.
o EAHEC – Entero-aggregative-haemorrhagic E. coli.
How Outbreaks are Identified
Possible epidemic case:
o Any person that has developed the symptoms AND has met a laboratory criteria (e.g. isolation of agent).
Probable epidemic case:
o Any person that has met the above criteria AND has been in epidemic country, consumed possibly contaminated food, been in close contact with a confirmed epidemic case.
Confirmed epidemic case:
o Any person meeting criteria for a possible case AND has had strain isolated.
PCR
The isolates can be screened by multiplex PCR for characteristic features of the outbreak strain.
o This can be done on stool samples for example (e. coli).
o This can determine if the strain is the outbreak strain or not.
Example E. coli outbreak:
o The unique combination of genomic features contained characteristics from both the EHEC and EAEC strains suggesting it represented a new strain EAHEC.
The PCR showed that the isolate contained aspects of both EHEC and EAEC:
EAEC – 2 plasmids:
o pAA-type plasmids – contain aggregative adhesion fimbrial operon.
o ESBL plasmids – gene encoding for extended-spectrum beta-lactamases.
EHEC – prophage – encoding the Shiga toxin – characteristic for EHEC strains.
Shiga toxins have an AB5 subunit composition.
o StxA is the enzymatic portion – cleaves RNA —> inhibition of protein synthesis and might affect gut commensal bacteria as well.
o StxB is the pentamer that binds to host cell receptors.
Shiga toxins are encoded on bacteriophages and contribute to horizontal gene transfer meaning they can be given to other bacteria types in phages.
EAEC can colonise the larger and small bowel —> affects gut flora.
EAECs virulence factor – Aggregative Adherence Fimbriae (AAF):
o AFF required for adhesion to enterocytes and stimulates IL-8 response.
o AFF also allows a biofilm formation.
List the communicable diseases in Europe.
1) Respiratory tract infections
2) Sexually transmitted infections, including HIV and blood-borne viruses
3) Food- and waterborne diseases and zoonoses
4) Emerging and vector-borne diseases
5) Vaccine-preventable diseases
6) Antimicrobial resistance and healthcare-associated infections
Describe respiratory tract infections.
Influenza
Animal influenzas, including avian influenza SARS - Severe acute respiratory syndrome
Legionnaires’ disease (legionellosis) Legionella pneumophila (Gram -)
Tuberculosis Mycobacterium tuberculosis (Gram +)
Legionella pneumophila
❖ Gram-negative bacterium
❖ Lives in amoeba in ponds, lakes, air conditioning units
❖ Infection route: inhalation of contaminated aerosols
❖ In humans L. pneumophila will infect and grow in aveolar macrophages
❖ Human infection is “dead end” for bacteria ❖ Important virulence factor type IV secretion system
Secretion of effector proteins by the type IV secretion system allows Legionella to replicate in a Legionella containing vacuole (LCV
Mycobacterium tuberculosis
❖ Groups with Gram-positive Mycobacterium tuberculosis bacteria
❖ very different cell wall – extra lipid layer makes treatment more difficult
❖ M. tuberculosis can enter a dormant state
Latent TB - evidence of infection by immunological tests but no clinical signs and symptoms of active disease
Treatment with antibiotics but takes at least 6 months
