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(dont affect mamals ,affects amphbian and reptiles) Zygomycota

Question 2

How different fungi enters the body and where they can affect

Answer 2

. Present in skin and gut and if something compromises the immmunity it can become infectious.

.Cryptococcus Neoformans are also inhaled and if you have a lack of CD4 T cells can goup to the brain from fungal balls and cause really unpleasant meningitis. Fungal balls can form and cause stroke like sumptoms in that individual.

Aspergillus fumigatus are inhaledas conidia(damage alveoli, no neutrophils germinates and form sfungal ball and leads to bleeding)

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 ofchronic mucocutaneous candidiasis.

Answer 4

Dectin 1 (involved in activation of an inflammatory cytokine response[

A loss of function mutation in HD1 leads to Mendelian susceptibility to chronic mucocutaneous candidiasis

* People with the homozygous mutation à reduced inflammatory response via IL-]) CARD 9 (downstream of Dectin 1[Functional CARD9 is required for TNF-alpha production in response to beta-glucan stimulation

* Functional CARD9 is required for T cell Th17 differentiation in humans])

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

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

Answer 24

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

Answer 25

F

Question 26

What are recognised for Signaling Pathways in Innate Recognition of Fungi

Answer 26

PAMPs and DAMPs

Question 27

What is dectin 1

Answer 27

A TLR