fungal infections Flashcards
what are the 3 main types of fungal spores
candida
cryptococcus
aspergillus
what are the virulence factors of these 3 types of fungal spore that allow for tissue invasion
Candida- dimorphism allows tissue invasion.
Cryptococcus- capsule evades phagocytosis.
Aspergillus- inhaled as conidia, invade as hyphae
what are fungi opsonised by
pentraxin-3
mannose binding lectin (MBL)
what are 3 diseases caused by these 3 fungal spores
- Candida albicans (thrush)
- Aspergillus (ABPA-Allergic bronchopulmonary aspergillosis)
- Cryptococcus (Cryptococcal meningitis)
what cells are critical in the first line defence against fungal infections
Phagocytes are a critical first line of defence
what do NK cells do against fungal infections
NK cells provide early interferon-gamma
what are the routes of infection of fungal infections
name spore type that uses each route
- Damaged epithelium (Candida)
- Inhalation and deposition in respiratory tract (Cryptococcus, Aspergillus)
- Direct inoculation into deep tissue, e.g. surgery, catherisation, intubation (Candida, Aspergillus)
what are the 3 lines of defence against fungal infection (very general)
1st line: physical barriers
2nd: innate immune system, phagocytosis APC etc
3rd line: Adaptive immune response ie T cell recruitment
what human deficiencies can increase risk to fungal infections
Human Dectin 1 Deficiency
Human CARD9 deficiency
TLR4 polymorphisms
Plasminogen alleles may also influence susceptibility to aspergillosis
how does Human CARD9 deficiency cause increased risk to fungal infections and which in particular
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
CARD-9 deficiency leads to chronic mucocutaneous candidiasis.
how does Human DECTIN-1 deficiency cause increased risk to fungal infections
this is normally important in the phagocytosis of Candida:
-chronic mucocutaneous candidiasis–>leads to massive hypertrophy of the mucosa and many problems with fungal drug resistance
Dectin 1 mutations–> increased susceptibility to invasive aspergillosis in SC transplantation
how does T4LR deficiency cause increased risk to fungal infections
TLR4 polymorphisms lead to an increased risk of Invasive Aspergillosis (IA) in transplanta
what are neutrophil nets
Neutrophil NETS: -neutrophils throw out chromatin “nets” to capture pathogens
what is the purpose of these neutrophil nets
These chromatin molecules outside the nucleus act as “danger signals” and recruit’s
effector cells to the area as
well
what is Fungal morphogenesis
fungi can transition between yeast, candida and hyphae forms (multicellular)
why is Fungal morphogenesis bad for the immune response
it can drive a modulation of Dendritic cell response and can be bad for the immune response (as it gets
confused)
what augments host immunity to fungal infections
Adaptive T-cell INF-gamma responses augment host immunity to fungi.
what type of hypersensitivity do important fungal infections use
Important fungal reactions include type 1, 3, 4 hypersensitivity reactions.
oT1: IgE-driven, involves histamine and leukotrienes, in minutes.
oT2: IgG, IgM-driven, involves complement, in 1-24 hours.
oT3: IgG, IgM-driven, involves complement, in 1-24 hours.
oT4: T-cell-driven, involves lymphokines, in 2-3 days
what are the diagnosis criteria for ABPA (Allergic Broncho-pulmonary Aspergillosis)
Criteria for diagnosis:
oPredisposing condition:–asthma or cystic fibrosis.
oObligatory criteria:–high baseline serum IgE, +ve T1 hypersensitivity (immediate response) skin test OR
Aspergillus-specific IgE.
oSupportive criteria (more than 2):–eosinophilia, IgG AB to Aspergillus fumigatus, consistent radiologic abnormalities
what conditions predispose to ABPA
asthma or cystic fibrosis.
what radiological abnormalities can be seen in ABPA
Radiologic abnormalities–also have hyper-dense mucus:
Dilated bronchi, thick walls. Upper/central predilection. Lobar collapse. Ring or linear opacities. Proximal bronchiectasis. Fibrotic scarring
