Fungal Immunity

Question 1

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

Answer 1

Ascomycota – MAIN ONE
Basidiomycota
Chytridiomycota
Zygomycota

Question 2

Give examples of how the morphogesis of fungi contributes to its ability to cause disease in the host.

Answer 2

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

Question 3

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

Answer 3

Toll like receptors

Question 4

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

Answer 4

Dectin 1 (involved in activation of an inflammatory cytokine response) 
CARD 9 (downstream of Dectin 1)

Question 5

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

Answer 5

TLR4 S4 – loss of function
Dectin 1
Plasminogen alleles

Question 6

Which PRR is actively recruited to Aspergillus fumigatusphagolysosomes?

Answer 6

TLR9

Question 7

What can plasminogen directly bind to?

Answer 7

Aspergillus fumigatus conidia

Question 8

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

Answer 8

Neutrophils

Question 9

What do neutrophils release that enable them to trap Aspergillus?

Answer 9

NETs

Question 10

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

Answer 10

Hyphal forms = Th2 response

Conidium = Th1 response

Question 11

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

Answer 11

IFN-gamma

Question 12

Describe the principles of adoptive immunotherapy for fungal infection.

Answer 12

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

Question 13

Give an example of gene therapy for chronic granulomatous disorder.

Answer 13

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

Question 14

What types of hypersensitivity reaction are associated with fungal allergies?

Answer 14

Type 1, 3 and 4

Question 15

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

Answer 15

Asthma

Cystic fibrosis

Question 16

What is the obligatory criteria for ABPA?

Answer 16

Total baseline serum IgE > 1000 IU/ml

Positive immediate hypersensitivity skin test or Aspergillus-specific IgE

Question 17

List some supportive criteria for ABPA.

Answer 17

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

Question 18

List some radiological features of ABPA.

Answer 18

Dilated bronchi with thick walls  
Proximal bronchiectasis  
Ring or linear opacities  
Upper or central region predilection  
Lobar collapse due to mucous impaction  
Fibrotic scarring

Question 19

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

Answer 19

Hyper dense mucous sign

Question 20

Describe the main treatment options for ABPA.

Answer 20

Corticosteroids
Itraconazole may be used as a steroid-sparing agent
Recombinant anti-IgE antibodies (omalizumab) may be useful

Question 21

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

Answer 21

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

Question 22

What test is used to diagnose fungal allergies?

Answer 22

Skin prick testing

Question 23

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

Answer 23

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

Question 24

How are fungi opsonised?

Answer 24

pentraxin-3 and mannose-binding lectin (MBL).