Immunity to fungal infections

Question 1

Cryptococcus neoformans - has a burden on humans, how?

Answer 1

It causes cryptococcal meningitis, especially in HIV patients

Question 2

Aside from cryptococcus neoformans, name another dangerous human fungal infection

Answer 2

Candida albicans - skin commensal

Can cause thrush and endophthalmitis (which may cause blindness) - again HIV patients more vulnerable

Question 3

Describe the cellular immunity processes in response to fungal infection

Answer 3

1. Opsonisation by pentraxin 3 and mannose-binding-lectin
2. Phagocytes (have PRRs - neutrophils and macrophages) = 1st line of defence
3. NK cells provide early IFN-gamma

If innate immunity fails, adaptive immunity:

Dendritic cells take up fungal antigens –> presented to T cells in draining nodes –> T cell differentiation. Th1 and Th17 important. Antibody production also important

Question 4

Describe fungal morphogenesis and virulence

Answer 4

Fungi can transform from unicellular to multicellular forms

Candidial dimorphism - allows tissue invasion

Cryptococcus (neoformans) forms capsule to evade phagocytosis

Aspergillus is inhaled as conidia, invades tissues as hyphae

Question 5

Toll receptors are innate PRRs needed for fungal immunity. What is the main fungal PRR in phagocytosis against mucocutaneous fungal infections?

Answer 5

Dectin 1

e.g. Candida

Question 6

What is the downstream adapter protein of Dectin paths

Answer 6

CARD9.

CARD9 is needed to make TNF-a in response to beta-glucan stimulation. CARD9 also needed for Th17 differentiation

Question 7

Mutations in which 3 things can lead to higher susceptibility to fungal disease

Answer 7

Dectin-1, TLR4, Plasminogen (plasminogen as you can get angioinvasion + thrombosis in some fungal disease)

TLR9 mutations linked to allergic fungal disease

Question 8

Neutrophils are very important for defence –> neutropenia is a serious risk for fungal infection. What is NET?

Answer 8

Neutrophil Extracellular Traps.

When neutrophils encounter large organisms –> neutrophils explode –> release DNA and nuclear proteins —> stimulating damage response + DNA binds to a. fumigatus —> prevents germination

Question 9

How does the response vary according to the fungal morphogenetic state

Answer 9

If unicellular fungi presented to DCs –> Th1 response (IL-12, IFN-gamma)

If multicellular/hyphae presented to DCs —> Th2 response (IL-4/10)

Mucosal immunity governs fungal tolerance and resistance

Question 10

Both macrophages and neutrophils are important in fungal immunity. But for aspergillus, which is more important

Answer 10

Neutrophil

Question 11

DCs modulate the adaptive immune response. Which responses may augment host immunity to fungi?

Answer 11

Adaptive T cell IFN-gamma responses

Question 12

Fungal allergies can be classed into type 1-4 hypersensitivity reactions. ABPA (allergic bronchopulmonary aspergillosis) is type?

Answer 12

1

No type 2 identified yet so effectively type 1, 3, 4

Question 13

Name some common environmental aspergilli that may cause fungal allergy

Answer 13

Aspergillus niger, a. fumigatus (may also cause lung infections in immunocompromised)

The aspergillus spore head is very small –> easily drawn into lungs

Question 14

Name some common fungal allergens that aren’t aspergilli

Answer 14

Alternaria (club shaped body)
Cladosporium
Penicillium

Question 15

What may predispose to Allergic Bronchopulmonary Aspergillosis

Answer 15

Predisposed by asthma and Cystic fibrosis

Also check if high IgE, eosinophilia and skin test (IgM)

Question 16

Describe how ABPA works

Answer 16

Allergy against aspergillus —> airway destruction —> airway widening —> mucous pooling —> more prone to infection

Question 17

What are the radiological signs of ABPA

Answer 17

Dilated bronchi with thickened walls, lobar collapse (due to mucus), fibrotic scarring

Question 18

How is ABPA treated

Answer 18

Corticosteroids –> reduce circulating IgE (or itraconazole for steroid sparing)

Question 19

Hypersensitivity pneumonitis requires?

Answer 19

Long term allergen exposure.

Hypersensitivity pneumonitis = cell mediated delayed hypersensitivity (type 4). Allergen specific precipitates usually seen.