Immunity to fungal infections Flashcards
What are the four main phyla of fungi and which most commonly causes human fungal infection?
Ascomycota – MAIN ONE
Basidiomycota
Zygomycota
Chytridiomycota (doesn’t really cause problems)
Important types of fungi known to cause human infection include?
Candida, Aspergillus and Cryptococcus species
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 patients are at risk of fungal infection and why?
Fungal pathogens are largely opportunists, only causing infections and disease when host defences are breached.
Those at risk:
- Patients with cancer because often they are immunocompromised, either because of their underlying malignancy and/or the treatment for their disease.
- AIDS patients
- Transplant recipients
Those at highest risk:
- Patients with prolonged and profound neutropenia after treatment with highly cytotoxic chemotherapy for haematological malignancies
- Recipients of haematopoietic stem cell transplantation
The immune response to fungi depends on what?
- species encountered
- anatomical site of infection
- fungal morphotype
State the important antifungal effector cells which form the first-line of defence of phagocytosis.
Neutrophils, macrophages and monocytes
As fungal cell walls are fundamentally different in their structure from human plasma membranes, what class of receptors are important in their detection?
Pattern recognition receptors of innate immunity
What are the ligands present on nearly all fungi?
1,3 β-glucans
Mannans
Chitin
List the PRRs for 1,3 β-glucans
Dectin-1 CR3 (CD11c/CD18) CD5 CD36 SCARF1
List the PRRs for Mannans
Mannose receptor (CD206)
DC-SIGN (CD209)
Langerin (CD207)
Dectin-2
State the PRR for Chitin
Mannose receptor (CD206)
Name another type of PRR involved in sensing other fungal components
Toll like receptors (TLRs)
Name 2 deficiencies that are associated with an increased risk of mucocutaneous fungal infections (namely chronic mucocutaneous candidiasis)
Dectin 1 deficiency => e.g. vulvovaginitis & onychomycosis
CARD 9 deficiency (CARD9 is an adaptor protein in the downstream pathway of Dectin 1)
Dectin 1 deficiency causes…
- impaired macrophage IL-6 production and binding in response to fungal infections.
- increased susceptibility to invasive aspergillosis in stem cell transplants.
CARD-9 is required for…
- TNFa production in response to b-glucan stimulation.
- T-cell Th17 differentiation
Mutations in what three things confer increased susceptibility to fungal disease?
TLR4
Dectin 1
Plasminogen
Which PRR is actively recruited to Aspergillus fumigatus phagolysosomes?
TLR9
What can plasminogen directly bind to?
Aspergillus fumigatus conidia
What do neutrophils release that enable them to trap Aspergillus?
NETs - chromatin “nets”.
These also act as “danger signals” and recruit’s effector cells to the area as well.
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 of invasive 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
