Flashcards in Fungal Immunity Deck (62):
Which phylum is the most common in causing human disease?
What is the appearance of aspergillus?
flowering- stalk with spores which germinate and form hyphae
Where does the cryptococcus neoformans that we breathe in all the time from?
trees and pigeons
Who gets cryptococcus neoformans?
people with defects in T cells e.g HIV/AIDs
How does cryptococcus avoid phagocytosis?
forms a capsule
Why does candida cause endophthalmitis?
gets stuck in microcapillaries
What are the opsonins in fungal infections?
pentraxin 3 and MBL
What type of T cells are protective in fungal infection?
Th1 and Th17
What are the 2 forms of candida?
yeast (circular cell form) and hyphal forms
Why does transitions between different forms of fungus cause problems in the host?
causes switching between protective (Th1/Th17) and non-protective (Th2) responses
What is aspergillus species inhaled as?
What form does aspergillus invade tissues as?
What is the classic DAMP signalling in fungal recognition?
What receptors are involved in the phagocytosis of fungi?
CTLRs, not TLRs
What 2 pathways are downstream of dectin-1 signalling?
inflammasome and NFkB
What does dectin-1 deficiency result in?
reduced IL-6 production and binding to candida--mucocutaneous fungal infections
What is required for NFkB activation by dectin-1?
What does homozygous CARD9 mutation result in?
chronic mucocutaneous candidiasis
What cytokine is CARD9 required for production in response to beta-glucans?
How is CARD9 invovled in T cell differentiation?
required for T cell Th17 differentiation
Deficiency in what TLR results in greater susceptibility to aspergillosis?
What effect does plasminogen have aspergillosis defense?
directly binds to aspergillus conidia and decreases susceptibility
How are macrophage depleted mice affected with aspergillus fumigatus?
not any more susceptible
Which cells are most important in defense against invasive aspergillosis?
neutrophils - as without have no ability to clear the infection
What effect does NET production have on aspergillus?
traps fungus and stops from germinating
How does the fungal morphogenesis affect T cell differentation?
different morphotypes are phagocytsed through different modalities by DCs which results in different mautration states
What is the effect of coiling phagocytosis vs zipper-type on DC maturation?
coiling results in increased IL-12 production whereas zipper-type results in increased IL-4 and IL10 production
What type of phagocytosis is used for single cell fungal morphology?
What type of phagocytosis is used for hyphase forms of fungi?
How does IFNy therapy aggect invasive fungal infection?
enhances clearance by down-regulating IL-10 and causing a burst of inflammatory cytokine expression
What is required for NET formation?
What are the emerging possibilities in the treatment of fungal infections?
IFN-y injections and adoptive T cells therapy (generation of antifungal T cells from stem cells and then injected in patients)
What are the main infections in patietns with CGD?
staph. and fungal infections
What are the common aspergillus species in the environment?
aspergillus niger and aspergillus fumigatus
What does the damage response framework describe?
that too weak or strong host responses to microbes can result in disease and death
What patients have a much higher incidence of mould allergy?
What are the 2 types of hypersensitivty reactions inovlved in ABPA?
type I and IV
What type of hypersensitivty reaction is hypersensitivity pneumonitis?
type III and IV
What is the main fungus invovled in allergy?
Why is there a suggestion that some of the damage in allergic disease to aspergillosis is autoimmune?
there is cross-reactiivity of one of hte main aspergillus allergens with human cyclophylin
What does ABPA stand for?
allergic bronchopulmonary aspergillosis
What diseases predispose to ABPA?
CF and asthma
What does hyphae formation allow the fungus to do?
germinate and proliferate
What are the obligatory criteria for ABPA?
IgE >1000; positive skin prick or aspergillus specific IgE
What are the radiological features of ABPA?
dilated bronchi with thick walls; ring/linear opacities; upper/central region prediliction; proximal bronchiectasis; lobar colllapse due to mucous impaction; fibrotic scarring
What sign is seen on CT with ABPA?
hyper dense mucus sign
What is the mainstya of treatment for ABPA?
What can be used as a steroid sparing agent in ABPA?
What is aspergillus rhinosinusitis associated with?
atopy and nasal polyposis
What is seen on imaging with aspergillus rhinosinusitis?
obliterated sinuses with hypo-attenuated mucosa and enhancing material
What are the 3 main cell wall components of funal species?
beta-glucans; chitin; mannans
What is the function of galectin 3 in fungal infection?
allows aphgocytes to discriminate between pathogenic and non-pathogenic yeats through recognition of beta-mannosides
What is the function of dectin-2 in fungal immunity?
high mannose structures that are common to many fungi and binds hyphal forms with higher affinity than yeast forms
What type of fungus infection are dectin-2 deficient mice susceptible to?
C.albicans but not C.neoformans
What other receptor does dectin-2 pair with to induce pro-inflammatory cytokines?
Fc receptor y chain
What is the function of DC-SIGN?
recognises N-linked mannans, and directs mannosylated fungal antigens into the DC endocytic pathway promoting antigen processing and presentation to T cells
What effect on fungal immunity does a polymorphism in TLR4 have ?
increased susceptibility to pulmonary aspergillosis and bloodstream candidiasis
What fungal disease is a polymorphism in the promoter region of TLR9 associated with?
What allows fungal escape of C.albicans by dectin-1?
beta glucans are exposed in the bud scar of C.albicans yeasts but masked on hyphae
How does P.jireveci evade immunosurveillance?
changes the expression of major surface glycoproteins
What is the function of hte capsule of C.neoformans?
completely covers the fungal cell wall and prevetns recognition by PRRs and the induction of inflammation