fungal infections

Question 1

what are the 3 main types of fungal spores

Answer 1

candida
cryptococcus
aspergillus

Question 2

what are the virulence factors of these 3 types of fungal spore that allow for tissue invasion

Answer 2

Candida- dimorphism allows tissue invasion.
Cryptococcus- capsule evades phagocytosis.
Aspergillus- inhaled as conidia, invade as hyphae

Question 3

what are fungi opsonised by

Answer 3

pentraxin-3

mannose binding lectin (MBL)

Question 4

what are 3 diseases caused by these 3 fungal spores

Answer 4

• Candida albicans (thrush)
• Aspergillus (ABPA-Allergic bronchopulmonary aspergillosis)
• Cryptococcus (Cryptococcal meningitis)

Question 5

what cells are critical in the first line defence against fungal infections

Answer 5

Phagocytes are a critical first line of defence

Question 6

what do NK cells do against fungal infections

Answer 6

NK cells provide early interferon-gamma

Question 7

what are the routes of infection of fungal infections

name spore type that uses each route

Answer 7

• Damaged epithelium (Candida)
• Inhalation and deposition in respiratory tract (Cryptococcus, Aspergillus)
• Direct inoculation into deep tissue, e.g. surgery, catherisation, intubation (Candida, Aspergillus)

Question 8

what are the 3 lines of defence against fungal infection (very general)

Answer 8

1st line: physical barriers
2nd: innate immune system, phagocytosis APC etc
3rd line: Adaptive immune response ie T cell recruitment

Question 9

what human deficiencies can increase risk to fungal infections

Answer 9

Human Dectin 1 Deficiency
Human CARD9 deficiency
TLR4 polymorphisms
Plasminogen alleles may also influence susceptibility to aspergillosis

Question 10

how does Human CARD9 deficiency cause increased risk to fungal infections and which in particular

Answer 10

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

CARD-9 deficiency leads to chronic mucocutaneous candidiasis.

Question 11

how does Human DECTIN-1 deficiency cause increased risk to fungal infections

Answer 11

this is normally important in the phagocytosis of Candida:
-chronic mucocutaneous candidiasis–>leads to massive hypertrophy of the mucosa and many problems with fungal drug resistance

Dectin 1 mutations–> increased susceptibility to invasive aspergillosis in SC transplantation

Question 12

how does T4LR deficiency cause increased risk to fungal infections

Answer 12

TLR4 polymorphisms lead to an increased risk of Invasive Aspergillosis (IA) in transplanta

Question 13

what are neutrophil nets

Answer 13

Neutrophil NETS: -neutrophils throw out chromatin “nets” to capture pathogens

Question 14

what is the purpose of these neutrophil nets

Answer 14

These chromatin molecules outside the nucleus act as “danger signals” and recruit’s
effector cells to the area as
well

Question 15

what is Fungal morphogenesis

Answer 15

fungi can transition between yeast, candida and hyphae forms (multicellular)

Question 16

why is Fungal morphogenesis bad for the immune response

Answer 16

it can drive a modulation of Dendritic cell response and can be bad for the immune response (as it gets
confused)

Question 17

what augments host immunity to fungal infections

Answer 17

Adaptive T-cell INF-gamma responses augment host immunity to fungi.

Question 18

what type of hypersensitivity do important fungal infections use

Answer 18

Important fungal reactions include type 1, 3, 4 hypersensitivity reactions.

oT1: IgE-driven, involves histamine and leukotrienes, in minutes.
oT2: IgG, IgM-driven, involves complement, in 1-24 hours.
oT3: IgG, IgM-driven, involves complement, in 1-24 hours.
oT4: T-cell-driven, involves lymphokines, in 2-3 days

Question 19

what are the diagnosis criteria for ABPA (Allergic Broncho-pulmonary Aspergillosis)

Answer 19

Criteria for diagnosis:

oPredisposing condition:–asthma or cystic fibrosis.

oObligatory criteria:–high baseline serum IgE, +ve T1 hypersensitivity (immediate response) skin test OR
Aspergillus-specific IgE.

oSupportive criteria (more than 2):–eosinophilia, IgG AB to Aspergillus fumigatus, consistent radiologic abnormalities

Question 20

what conditions predispose to ABPA

Answer 20

asthma or cystic fibrosis.

Question 21

what radiological abnormalities can be seen in ABPA

Answer 21

Radiologic abnormalities–also have hyper-dense mucus:

Dilated bronchi, thick walls.
Upper/central predilection.
Lobar collapse.
Ring or linear opacities.
Proximal bronchiectasis.
Fibrotic scarring