immunity to fungal infections

Question 1

what are fungi opsonised by?

Answer 1

• pentraxin-3

- mannose binding lecton

Question 2

what are the cells involved in immunity to fungal infection?

Answer 2

• phagocytes = first line defence
• NK cells = provide early INF-gamma
• dendritic cells = influence T cell differentiation
• Th1 and Th17

Question 3

what is the virulence of candida, crytopococcus and aspergillus?

Answer 3

• candida: dimorphism allows tissue invasion
• crytococcus: capsule evades phagocytosis
• aspergillus: inhaled as conidia, invade as hyphae

Question 4

mutations in which genes lead to increased susceptibilty to fungal disease?

Answer 4

• dectin-1
• TLR4
• plasminogen

Question 5

what is dectin-1?

Answer 5

fungal PRR

Question 6

what does a dectin-1 deficiency lead to?

Answer 6

• mucocutanteous fungal infections e.g. vulvovaginitis
• leads to imapired macrophage IL-6 production and binding in response to fungal infections
• inc. susceptibilty to invasive aspergillosis in stem cell transplants

Question 7

what is CARD-9 required for?

Answer 7

• TNF alpha production in response to beta-glucan stimulation
• T cell Th17 differentiation

Question 8

what does a CARD-9 def lead to?

Answer 8

chronic mucocutaneous candidiasis

Question 9

What does a TLR4 polymorphism do?

Answer 9

• leads to inc. risk of invasive aspergillus in transplantation

Question 10

what main blood cell is important in fungal cellular defence?

Answer 10

Neutrphils

• neutrophil nets throw out chromatin nets to capture pathogens
• chromatin molecules outside nucleus act as “danger signals”, recruits effector cells to area

Question 11

what is fungal morphogenesis and why is it bad for immune response?

Answer 11

• fungi can transition between yeast, candida, hyphae forms
• this can drive modulation of dendritic cell response
• immune system gets confused

Question 12

what are treatment options?

Answer 12

• adoptive immunotherapy: generate lots of antifungal T-cells in sample, give these pt
• gene therapy: restore gp91 function (make reactive oxidative species to fight fungal spores)

Question 13

what can the host response to fungal spores be?

Answer 13

• normal, ineffective or exaggerated (allergy)

- leads to either an allergic or invasive fungal disease

Question 14

what is the primary driver?

Answer 14

• aspergillus
• other fungi may contribute
• e.g. aspergillus niger, aspergilla fumigatus
• other supporting fungi = Alternaria, Clodosporium, Penicillium

Question 15

what are the important fungal reaction types?

Answer 15

Type 1,2,3,4 hypersensitivity reactions
T1: IgE driven, involved histamine and leukotrienes (mins)
T2: IgG, IgM-driven, involves complement (1-24 hours)
T3: IgG, IgM driven, involved complement
T4: T cell driven, involves lymphokines, in 2-3 days

Question 16

name the best recognised pulmonary allergy to fungi?

Answer 16

ABPA (allergic bronchopulmonary aspergillosis)

Question 17

what is the criteria for diagnosis of ABPA?

Answer 17

• predisposing diagnosis (asthma or CF)
• obligatory criteria (high baseline IgE, +ve T1 hypersensitivity skin test or aspergillus-specific IgE)
• supportive criteria, more than 2 (eosinophila, IgG AB to aspergillus fumigatus, consistent radiologic abnormalities)

Question 18

what are the different radiologic abnormalities?

Answer 18

• dilated bronchi, thick walls
• ring or linear opacities
• upper/central prefilection
• lobar collapse
• fibrotic scarring

Question 19

what is the management of ABPA?

Answer 19

• corticosteroids
• itraconazole (steroid sparing agent)
• omalizumab (recombinant IgE monoclonal ABS may be useful)

Question 20

how do diagnose pulmonary allergies to fungi?

Answer 20

• skin tests

- IgE and IgM