What are the four main phyla of fungi and which most commonly causes human fungal infection?
Ascomycota – MAIN ONE Basidiomycota Chytridiomycota - doesn't usally cause human infection as it is water bound Zygomycota
Give examples of how the morphogesis of fungi contributes to its ability to cause disease in the host.
Candida albicans exist as single spores but they can become hyphae, which allows tissue invasion Cryptococcus forms a capsule to evade phagocytosis Aspergillus sp. are inhaled as conidia and invade tissues as hyphae
Which pattern recognition receptors are important in detection of fungal pathogens?
Name 2 deficiencies that are associated with an increased risk of chronic mucocutaneous candidiasis.
Dectin 1 - an important c type lectin for candida infections, involved in activation of an inflammatory cytokine response CARD 9 (downstream of Dectin 1)
Name 3 factors that are associated with increased risk of Aspergillosis in transplantation.
TLR4 S4 – loss of function Dectin 1 Plasminogen alleles
Which PRR is actively recruited to Aspergillus fumigatus phagolysosomes?
What can plasminogen directly bind to?
Aspergillus fumigatus conidia
Which cells are the most important in defence against fungal infection?
Neutrophils - particularly for aspergillus Without them the fungus grows like it would in a nutrient rich broth
What do neutrophils release that enable them to trap Aspergillus?
NETs - made of DNA
Describe how fungal morphogenesis governs the dendritic cell modulation of adaptive immunity.
Multicellular Hyphal forms = Th2 IL-4/IL-10 response Conidium = Th1 IFN-g/IL-12 response
What cytokine therapy has been shown to enhance clearance of invasive fungal infection?
Describe the principles of adaptive immunotherapy for fungal infection.
If a patient is receiving a stem cell transplant, you can generate anti-fungal T cells, which can be cultured in large numbers and administered to the patient
Give an example of gene therapy for chronic granulomatous disorder.
Restoration of gp91 function This is involved in the generation of NADPH oxidase – this generates reactive oxygen species, which is required to kill microbes NOTE: another type of gene therapy = restoration of neutrophil NET formation
What types of hypersensitivity reaction are associated with fungal allergies?
Type 1, 3 and 4
What are two predisposing conditions for allergic bronchopulmonary aspergillosis (ABPA)?
Asthma Cystic fibrosis
What is the obligatory criteria for ABPA?
Total baseline serum IgE > 1000 IU/ml Positive immediate hypersensitivity skin test or Aspergillus-specific IgE
List some supportive criteria for ABPA.
Eosinophilia > 500 cells/ul Serum precipitating or IgG antibodies to Aspergillus fumigatus Consistent radiographic abnormalities
List some radiological features of ABPA.
Dilated bronchi with thick walls Proximal bronchiectasis Ring or linear opacities Upper or central region predilection Lobar collapse due to mucous impaction Fibrotic scarring
What might be seen in a CT scan of a patient with ABPA?
Hyper dense mucous sign
Describe the main treatment options for ABPA.
Corticosteroids Itraconazole may be used as a steroid-sparing agent Recombinant anti-IgE antibodies (omalizumab) may be useful
List three examples of fungal allergies other than ABPA, including associated features of each.
- Aspergillus rhinosinusitis
- May be allergic or invasive
- Obliterated sinuses
- Treated with oral corticosteroids and surgical removal of obstructing nasal tissue
- Severe asthma with fungal sensitisation
- Fungal sensitisation as a potential cause of severe asthma
- Requires exclusion of ABPA
- Treatment with anti-fungal unclear
- Hypersensitivity pneumonitis (extrinsic allergic alveolitis)
- Allergy requires long-term exposure to allergen (often occupational)
What test is used to diagnose fungal allergies?
Skin prick testing
Which type of hypersensitivity is each of the previously mentioned fungal allergies?
ABPA – type 1 or 4 Asthma – type 1 Rhinitis – type 1 Hypersensitivity pneumonitis – type 4
What is the main infection in AIDS patients?
Where is candida found?
As a commensal in the skin and gut
Which immune receptor system is key for fungal immunity?
Toll like receptors C type lectins Scavenger receptors DAMPS
What are c type lectins?
Receptors that sense carbohydrate in fungal cell walls and are very important for phagocytosis
What does Th17 activation depend on?
CARD 9 Innate immunity priming
Which T cells are imporant for mucosal immunity?
What do DAMPS detect?
Intraceullular components e.g. DNA, histones actin, in the exracellular space