Immunity to fungal infections Flashcards
how do cells develop immunity to fungal infection?
- Fungi are made more susceptible to phagocytosis by pentraxin-3 and mannose-binding lectin (MBL)
- the cells involved in providing immunity to fungal infections are the following:
- Phagocytes – are the first line of defense
- NK cells – provide early INF-gamma
- Dendritic cells – influence T-cell differentiation. Th1 and Th17 cells.
how do specific fungal spores become more infectious? x3
(virulence)
Candida – dimorphism allows tissue invasion
Cryptococcus – capsule evades phagocytosis
Aspergillus – inhaled as conidia, invade as hyphae.
how do flies stay immune to fungal infection?
- Toll is an innate PRR (that is required for fungal immunity
what human deficiencies lead to fungal infections?
- Dectin 1 (a fungal pattern recognition receptor) deficiency
- CARD 9 deficiency
how might a Dectin 1 deficiency cause lead to fungal infection?
- Dectin 1 deficiency leads to mucocutaneous fungal infections, for example, vulvovaginitis & onychomycosis
- Dectin 1 deficiency leads to impaired macrophage IL-6 production and binding in response to fungal infections
- Dectin 1 deficiency also leads to susceptibility to invasive aspergillosis in stem cell transplants.
how might a CARD 9 deficiency cause lead to fungal infection?
- CARD-9 deficiency leads to chronic mucocutaneous candidiasis.
- this is because CARD 9 is needed for
- TNF production in response to b-glucan stimulation.
- T-cell Th17 differentiation.
what do TLR4 polymorphisms lead to?
- might lead to increased risk of invasive Aspergillosis in transplantation
(i. e. hematopoietic stem cell transplants)
what also might cause susceptibility to invasive fungal infections and disease?
- there are a range of major SNPs (single nucleotide polymorphisms) which are associated with increased susceptibility to invasive fungal disease
what are the cellular defenses to fungal infections?
- Neutrophilic defense (important for Aspergillus)
- macrophages
how do neutrophils defend against fungal infections?
- they make neutrophil nets - this is when neutrophils throw out chromatin “nets” to capture pathogens.
- these chromatin molecules also act as danger signals and recruit effector cells to the area
what is Fungal morphogenesis?
- fungi can transition between yeast, candida and hyphae forms
- this can drive modulation of dendritic cell response and can confuse the immune system
what are innate defense mechanisms against fungal infection?
- Mucosal immunity
innate mucosal immunity governs fungal tolerance and resistance.
how to treat fungal infections? x2
- adoptive immunotherapy
- gene therapy
how does adoptive immunotherapy work?
- we generate lots of anti-fungal T cells in a sample and give it to the patient to fight the fungal infection
how does gene therapy work?
- works by editing a gene to restore a function
- for example:
- restore gp91 function
- by restoring gp91 function we are able to make reactive oxidative species to fight fungal spores
- another example :
- might be to restore the ability to restore the neutrophil net formation
- these work by restoring the initial primary immunodeficiencies
