Fungal Immunity

Question 1

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

Answer 1

Ascomycota (MAIN)
Basidiomycota
Chytridiomycota
Zygomycota

Question 2

Give 3 examples of how the morphogenesis of fungi contributes to its ability to cause disease in the host.

Answer 2

Candida albicans exist as single spores but can become hyphae, allowing tissue invasion
Cryptococcus forms a capsule to evade phagocytosis
Aspergillus sp. are inhaled as conidia + 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 of chronic mucocutaneous candidiasis.

Answer 4

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

Question 5

Name 3 factors that are associated with increased risk of fungal disease

Answer 5

TLR4 S4 loss of function mutation
Dectin 1 mutations
Plasminogen alleles

Question 6

What can plasminogen directly bind to?

Answer 6

Aspergillus fumigatus conidia

Question 7

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

Answer 7

Neutrophils

Question 8

What do neutrophils release that enable them to trap Aspergillus?

Answer 8

NETs

Question 9

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

Answer 9

Hyphal forms = Th2 response

Conidium = Th1 response

Question 10

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

Answer 10

IFN-gamma

Question 11

Describe the principles of adoptive immunotherapy for fungal infection.

Answer 11

If patient receiving a stem cell transplant, you can generate anti-fungal T cells, which can be cultured in large numbers + administered to the patient

Question 12

Give 2 examples of gene therapy for chronic granulomatous disorder.

Answer 12

1. Restoration of gp91 function
   Involved in generation of NADPH oxidase: generates reactive oxygen species, which is required to kill microbes
2. Restoration of neutrophil NET formation

Question 13

What types of hypersensitivity reaction are associated with fungal allergies?

Answer 13

Type 1, 3 + 4

Question 14

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

Answer 14

Asthma

Cystic fibrosis

Question 15

What is the obligatory criteria for ABPA?

Answer 15

Elevated baseline serum IgE

Positive immediate hypersensitivity skin test or Aspergillus-specific IgE

Question 16

List 3 supportive criteria for ABPA.

Answer 16

Eosinophilia
Serum precipitating or IgG antibodies to Aspergillus fumigatus
Consistent radiographic abnormalities

Question 17

List 6 radiological features of ABPA.

Answer 17

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 18

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

Answer 18

Hyper dense mucous sign

Question 19

Describe the main treatment options for ABPA.

Answer 19

Corticosteroids
Antifungals (Itraconazole for steroid-sparing agent )
Recombinant anti-IgE antibodies (omalizumab)

Question 20

List 3 other examples of fungal allergies, including associated features of each.

Answer 20

1. Aspergillus rhinosinusitis:
   Allergic or invasive
   Raised serum IgE
   Obliterated sinuses
   Treated with oral corticosteroids
2. Severe asthma with fungal sensitisation:
   Fungal sensitisation as a potential cause of severe asthma
   Requires exclusion of ABPA
   Treatment with anti-fungal unclear
3. Hypersensitivity pneumonitis:
   Allergy requires long-term exposure to allergen (often occupational)
   Cell mediated delayed sensitivity reaction

Question 21

What test is used to diagnose fungal allergies?

Answer 21

Skin prick testing

Question 22

Which type of hypersensitivity is each of the following fungal allergies? 
ABPA
Asthma
Rhinitis
Hypersensitivity pneuomonitis

Answer 22

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

Question 23

List 4 cellular mechanisms of anti fungal defence

Answer 23

Opsonisation of antigens by pentraxin 3 + mannose binding lectin
Phagocytes = first line of defence
NK cells produce interferon gamma
Failure of innate leads to adaptive, with DC influencing T cell differentiation