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Flashcards in Fungal Immunity Deck (33)
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1

What are the four main phyla of fungi and which most commonly causes human fungal infection?

Ascomycota – MAIN ONE Basidiomycota Chytridiomycota - doesn't usally cause human infection as it is water bound Zygomycota

2

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

3

Which pattern recognition receptors are important in detection of fungal pathogens?

TLR

4

Name 2 deficiencies that are associated with an increased risk of chronic mucocutaneous candidiasis.

Dectin 1 - an important c type lectin for candida infections, involved in activation of an inflammatory cytokine response CARD 9 (downstream of Dectin 1)

5

Name 3 factors that are associated with increased risk of Aspergillosis in transplantation.

TLR4 S4 – loss of function Dectin 1 Plasminogen alleles

6

Which PRR is actively recruited to Aspergillus fumigatus phagolysosomes?

TLR9

7

What can plasminogen directly bind to?

Aspergillus fumigatus conidia

8

Which cells are the most important in defence against fungal infection?

Neutrophils - particularly for aspergillus Without them the fungus grows like it would in a nutrient rich broth

9

What do neutrophils release that enable them to trap Aspergillus?

NETs - made of DNA

10

Describe how fungal morphogenesis governs the dendritic cell modulation of adaptive immunity.

Multicellular Hyphal forms = Th2 IL-4/IL-10 response Conidium = Th1 IFN-g/IL-12 response

11

What cytokine therapy has been shown to enhance clearance of invasive fungal infection?

IFN-gamma

12

Describe the principles of adaptive 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

13

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

14

What types of hypersensitivity reaction are associated with fungal allergies?

Type 1, 3 and 4

15

What are two predisposing conditions for allergic bronchopulmonary aspergillosis (ABPA)?

Asthma Cystic fibrosis

16

What is the obligatory criteria for ABPA?

Total baseline serum IgE > 1000 IU/ml Positive immediate hypersensitivity skin test or Aspergillus-specific IgE

17

List some supportive criteria for ABPA.

Eosinophilia > 500 cells/ul Serum precipitating or IgG antibodies to Aspergillus fumigatus Consistent radiographic abnormalities

18

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

19

What might be seen in a CT scan of a patient with ABPA?

Hyper dense mucous sign

20

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

21

List three examples of fungal allergies other than ABPA, including associated features of each.

  1. Aspergillus rhinosinusitis 
  • May be allergic or invasive
  •  Obliterated sinuses
  • Treated with oral corticosteroids and surgical removal of obstructing nasal tissue
  1. Severe asthma with fungal sensitisation 
  • Fungal sensitisation as a potential cause of severe asthma 
  •  Requires exclusion of ABPA
  • Treatment with anti-fungal unclear
  1. Hypersensitivity pneumonitis (extrinsic allergic alveolitis)
  •  Allergy requires long-term exposure to allergen (often occupational)

22

What test is used to diagnose fungal allergies?

Skin prick testing

23

Which type of hypersensitivity is each of the previously mentioned fungal allergies?

ABPA – type 1 or 4 Asthma – type 1 Rhinitis – type 1 Hypersensitivity pneumonitis – type 4

24

What is the main infection in AIDS patients?

Cryptococcus neoformans

25

Where is candida found?

As a commensal in the skin and gut

26

Which immune receptor system is key for fungal immunity?

Toll like receptors C type lectins Scavenger receptors DAMPS

27

What are c type lectins?

Receptors that sense carbohydrate in fungal cell walls and are very important for phagocytosis

28

What does Th17 activation depend on?

CARD 9 Innate immunity priming

29

Which T cells are imporant for mucosal immunity?

TH17

30

What do DAMPS detect?

Intraceullular components e.g. DNA, histones actin, in the exracellular space