What are the four main phyla of fungi and which most commonly causes human fungal infection?
Ascomycota – MAIN ONE Basidiomycota Chytridiomycota(dont affect mamals ,affects amphbian and reptiles) Zygomycota
How different fungi enters the body and where they can affect
. Present in skin and gut and if something compromises the immmunity it can become infectious.
.Cryptococcus Neoformans are also inhaled and if you have a lack of CD4 T cells can goup to the brain from fungal balls and cause really unpleasant meningitis. Fungal balls can form and cause stroke like sumptoms in that individual.
Aspergillus fumigatus are inhaledas conidia(damage alveoli, no neutrophils germinates and form sfungal ball and leads to bleeding)
Which pattern recognition receptors are important in detection of fungal pathogens?
Name 2 deficiencies that are associated with an increased risk ofchronic mucocutaneous candidiasis.
Dectin 1 (involved in activation of an inflammatory cytokine response[
A loss of function mutation in HD1 leads to Mendelian susceptibility to chronic mucocutaneous candidiasis
* People with the homozygous mutation à reduced inflammatory response via IL-]) CARD 9 (downstream of Dectin 1[Functional CARD9 is required for TNF-alpha production in response to beta-glucan stimulation
* Functional CARD9 is required for T cell Th17 differentiation in humans])
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?
What can plasminogen directly bind to?
Aspergillus fumigatus conidia
Which cells are the most important in defence against fungal infection?
What do neutrophils release that enable them to trap Aspergillus?
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?
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
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
What are recognised for Signaling Pathways in Innate Recognition of Fungi
PAMPs and DAMPs
What is dectin 1