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 - doesn’t usally cause human infection as it is water bound 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

TLR

Question 4

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

Answer 4

Dectin 1 - an important c type lectin for candida infections, 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 fumigatus phagolysosomes?

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

Question 9

What do neutrophils release that enable them to trap Aspergillus?

Answer 9

NETs - made of DNA

Question 10

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

Answer 10

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

Question 11

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

Answer 11

IFN-gamma

Question 12

Describe the principles of adaptive 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 examples of fungal allergies other than ABPA, including associated features of each.

Answer 21

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)

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

What is the main infection in AIDS patients?

Answer 24

Cryptococcus neoformans

Question 25

Where is candida found?

Answer 25

As a commensal in the skin and gut

Question 26

Which immune receptor system is key for fungal immunity?

Answer 26

Toll like receptors C type lectins Scavenger receptors DAMPS

Question 27

What are c type lectins?

Answer 27

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

Question 28

What does Th17 activation depend on?

Answer 28

CARD 9 Innate immunity priming

Question 29

Which T cells are imporant for mucosal immunity?

Answer 29

TH17

Question 30

What do DAMPS detect?

Answer 30

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

Question 31

What immune cells are important for Strep infections?

Answer 31

CD4+ T-cells

Question 32

What fungus commonly cause allergic reactions?

Answer 32

Candida Alternaria Aspergillus (primary driver)

Question 33

Summarise the different hypersensitivity reactions

Answer 33