Fungal Immunity Flashcards
What are the four main phyla of fungi and which most commonly causes human fungal infection?
Ascomycota (MAIN)
Basidiomycota
Chytridiomycota
Zygomycota
Give 3 examples of how the morphogenesis of fungi contributes to its ability to cause disease in the host.
Candida albicans exist as single spores but can become hyphae, allowing tissue invasion
Cryptococcus forms a capsule to evade phagocytosis
Aspergillus sp. are inhaled as conidia + invade tissues as hyphae
Which pattern recognition receptors are important in detection of fungal pathogens?
Toll like receptors
Name 2 deficiencies that are associated with an increased risk of chronic mucocutaneous candidiasis.
Dectin 1 (PRR involved in activation of an inflammatory cytokine response) CARD 9 (gene downstream of Dectin 1)
Name 3 factors that are associated with increased risk of fungal disease
TLR4 S4 loss of function mutation
Dectin 1 mutations
Plasminogen alleles
What can plasminogen directly bind to?
Aspergillus fumigatus conidia
Which cells are the most important in defence against fungal infection?
Neutrophils
What do neutrophils release that enable them to trap Aspergillus?
NETs
Describe how fungal morphogenesis governs the dendritic cell modulation of adaptive immunity.
Hyphal forms = Th2 response
Conidium = Th1 response
What cytokine therapy has been shown to enhance clearance of invasive fungal infection?
IFN-gamma
Describe the principles of adoptive immunotherapy for fungal infection.
If patient receiving a stem cell transplant, you can generate anti-fungal T cells, which can be cultured in large numbers + administered to the patient
Give 2 examples of gene therapy for chronic granulomatous disorder.
- Restoration of gp91 function
Involved in generation of NADPH oxidase: generates reactive oxygen species, which is required to kill microbes - Restoration of neutrophil NET formation
What types of hypersensitivity reaction are associated with fungal allergies?
Type 1, 3 + 4
What are two predisposing conditions for allergic bronchopulmonary aspergillosis (ABPA)?
Asthma
Cystic fibrosis
What is the obligatory criteria for ABPA?
Elevated baseline serum IgE
Positive immediate hypersensitivity skin test or Aspergillus-specific IgE
List 3 supportive criteria for ABPA.
Eosinophilia
Serum precipitating or IgG antibodies to Aspergillus fumigatus
Consistent radiographic abnormalities
List 6 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
Antifungals (Itraconazole for steroid-sparing agent )
Recombinant anti-IgE antibodies (omalizumab)
List 3 other examples of fungal allergies, including associated features of each.
- Aspergillus rhinosinusitis:
Allergic or invasive
Raised serum IgE
Obliterated sinuses
Treated with oral corticosteroids - 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:
Allergy requires long-term exposure to allergen (often occupational)
Cell mediated delayed sensitivity reaction
What test is used to diagnose fungal allergies?
Skin prick testing
Which type of hypersensitivity is each of the following fungal allergies? ABPA Asthma Rhinitis Hypersensitivity pneuomonitis
ABPA – type 1 or 4
Asthma – type 1
Rhinitis – type 1
Hypersensitivity pneumonitis – type 4
List 4 cellular mechanisms of anti fungal defence
Opsonisation of antigens by pentraxin 3 + mannose binding lectin
Phagocytes = first line of defence
NK cells produce interferon gamma
Failure of innate leads to adaptive, with DC influencing T cell differentiation
