Fungal Immunity Flashcards
(23 cards)
What are the four main phyla of fungi and which most commonly causes human fungal infection?
Ascomycota – MAIN ONE
Basidiomycota
Chytridiomycota
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?
TLR
Name 2 deficiencies that are associated with an increased risk ofchronic mucocutaneous candidiasis.
Dectin 1 (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 fumigatusphagolysosomes?
TLR9
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 ofinvasive fungal infection?
IFN-gamma
Describe the principles of adoptive 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 other examples of fungal allergies, including associated features of each.
Aspergillus rhinosinusitis
May be allergic or invasive
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 (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
