Fungal Immunity Flashcards
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 which normally affect mucosal tissues but they can become hyphae, which allows tissue invasion
Cryptococcus neoformans 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- toll like receptor
Name 2 deficiencies that are associated with an increased risk of chronic 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- especially aspergillus
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
What test is used to diagnose fungal allergies?
Skin prick testing
IgE and IgM
Overview of immunity to fungal infections
Opsonisation occurs
Phagocytes important first line defense
NK cells produce interferon gamma
Dendritic cells produce cytokines to affect t-cell differentiation
TH1 and Th17 play a role
MUCOSAL IMMUNITY TENDS TO DETERMINE RESPONSE AND IS MOST IMPORTANT
What do fungae normally exist as
Unicellular oragnisms
What is name given to when when become multicellular
Hypha
How do dectin 1 and card 9 deficiencies lead to increased risk of fungal infections
These are found on phagocytes- their pathway activation leads to inflammatory response and cytokine production
Do we inhale may fungal spores daily
yes
What happens when host response to fungal inhalation is inadequate
Invasive fungal disease
What happens when fungal inhalation response is exaggerated
Allergy- asthma or rhinitis
Main driver between fungal allergy and disease
Aspergillis
