fungal infections

Question 1

what are fungi opsonised by

Answer 1

pentraxin-3 and MBL

Question 2

5 cells involved in fungal infection

Answer 2

phagocytes (first line), NK cells (provide early INF-gamma), dendritic cells (influence T cell differentiation), Th1 and Th17

Question 3

what allows tissue invasion in candida virulence

Answer 3

dimorphism

Question 4

what allows cryptococcus to evade phagocytosis

Answer 4

capsule

Question 5

how are aspergillus inhaled and invade as

Answer 5

inhaled as candida, invade as hyphae

Question 6

how do toll receptors play an important role in phagocytosis

Answer 6

toll is innate pattern recognition receptor required for fungal immunity

Question 7

3 human deficiencies leading to fungal infections

Answer 7

dectin 1, CARD-9, TLR4 polymorphism

Question 8

describe what dectin 1 (fungal pattern recognition receptor) deficiency leads to

Answer 8

leads to mucocutaneous fungal infections, leading to impaired macrophage IL-6 production and binding in response to fungal infections, and leads to increased susceptibility to invasive aspergillosis in stem cell transplants

Question 9

describe what CARD-9 deficiency leads to

Answer 9

leads to chronic mucocutaneous candidiasis

Question 10

what is CARD-9 required for

Answer 10

TNF-a production in response to B-glucan stimulation, T-cell Th17 differentiation

Question 11

what do TLR4 polymorphisms lead to

Answer 11

increased risk of invasive aspergillosis in transplantation

Question 12

what are there many of which are associated with increased susceptibility to invasive fungal infections and disease

Answer 12

major SNPs

Question 13

what 3 mutations can confer increased susceptibility to fungal disease

Answer 13

mutations on dectin-1, TLR4 and plasminogen

Question 14

what cells are very important in fungal defence

Answer 14

neutrophils

Question 15

describe neutrophil nets and function

Answer 15

neutrophils throw out chomatin nets to capture pathogens, with chromatin molecules outside nucleus acting as danger signals and recruit effector cells to area

Question 16

describe fungal morphogenesis, and how this can be bad for immune response

Answer 16

fungi can transition between yeast, candida and hyphae forms (multicellular) and this can drive a modulation of dendritic cell response and can be bad for the immune response (as it gets confused)

Question 17

what governs fungal tolerance and resistance

Answer 17

mucosal innate immunity

Question 18

2 forms of treatment for fungal infections

Answer 18

adoptive immunotherapy, gene therapy

Question 19

what does adoptive immunotherapy do

Answer 19

generates lots of antifungal T-cells in a sample, and give these to patients that need to fight a fungal infection

Question 20

what happens in gene therapy to treat chronic granulomatous disorder

Answer 20

restore gp91 function (make reactive oxidative species to fight fungal spores) to treat chronic granulomatous disorder (restore neutrophil net formation)

Question 21

what 2 white cells contribute to fungal immunity

Answer 21

macrophages and neutrophils (neutrophuls are primary important in aspergillus)

Question 22

what do dendritic cells do

Answer 22

modulate adaptive immune responses

Question 23

what responses augment host immunity to fungi

Answer 23

adaptive T-cell INF-gamma responses

Question 24

2 possible new treatments for fungal infections

Answer 24

INF-gamma or adoptive T-cell therapy, gene therapy for primary immunodeficiencies

Question 25

3 types of host response to fungal spore inhalation, and what these can lead to

Answer 25

normal, ineffective or exaggerated (allergy), leading to allergic or invasive fungal disease

Question 26

what fungas is a primary driver of fungal allergy

Answer 26

Aspergillus (but other supporting fungi e.g. penicillum)

Question 27

what hypersensitivity reactions are included in important fungal reactions

Answer 27

type 1, 3 and 4

Question 28

what is a type 1 hypersensitivity reaction

Answer 28

IgE driven, involves histamine and leukotrienes, in minutes

Question 29

what is a type 3 hypersensitivity reaction

Answer 29

IgG, IgM driven, involves complement, in 1-24 hours

Question 30

what is a type 4 hypersensitivity reaction

Answer 30

T-cell driven, involves lymphokines, in 2-3 days

Question 31

describe fungi allergens variation and consequence

Answer 31

multiple allergens per fungi, which all cross-react and cross-sensitise to post-proteins, causing an autoimmune response

Question 32

describe pathophysiology of allergic bronchopulmonary aspergillosis

Answer 32

inhale spores -> abnormalities in dendritic cells so Th17 responses in lungs -> B-cells produce IgE -> mast cell granulation and eosinophilia

Question 33

criteria for allergic bronchopulmonary aspergillosis diagnosis

Answer 33

predisposing condition (asthma, CF), obligatory criteria (high baseline IgE, positive type 1 hypersensitivity skin test or aspergillus specific IgE), supportive criteria (eosinophilia, IgG to aspergillus, consistent radiological abnormalities)

Question 34

describe radiological abnormalities which can be seen in allergic bronchopulmonary aspergillosis

Answer 34

hyper-dense mucus, dilated bronchi with thick walls, ring/linear opacities, upper/central predilection, proximal bronchiectasis, lobar collapse, fibrotic scarring

Question 35

3 managements of allergic bronchopulmonary aspergillosis

Answer 35

corticosteroids, itraconazole (steroid-sparing agent; if not responding to steroids or if steroid-dependency), omalizumab (recombinant IgE monoclonal antibodies)

Question 36

what is the best pulmonary allergy to fungi

Answer 36

allergic bronchopulmonary aspergillosis