Fungal Immunity Flashcards

1
Q

Which phylum is the most common in causing human disease?

A

ascomyota

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2
Q

What is the appearance of aspergillus?

A

flowering- stalk with spores which germinate and form hyphae

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3
Q

Where does the cryptococcus neoformans that we breathe in all the time from?

A

trees and pigeons

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4
Q

Who gets cryptococcus neoformans?

A

people with defects in T cells e.g HIV/AIDs

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5
Q

How does cryptococcus avoid phagocytosis?

A

forms a capsule

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6
Q

Why does candida cause endophthalmitis?

A

gets stuck in microcapillaries

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7
Q

What are the opsonins in fungal infections?

A

pentraxin 3 and MBL

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8
Q

What type of T cells are protective in fungal infection?

A

Th1 and Th17

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9
Q

What are the 2 forms of candida?

A

yeast (circular cell form) and hyphal forms

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10
Q

Why does transitions between different forms of fungus cause problems in the host?

A

causes switching between protective (Th1/Th17) and non-protective (Th2) responses

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11
Q

What is aspergillus species inhaled as?

A

conidia

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12
Q

What form does aspergillus invade tissues as?

A

hyphae

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13
Q

What is the classic DAMP signalling in fungal recognition?

A

S100B-RAGE

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14
Q

What receptors are involved in the phagocytosis of fungi?

A

CTLRs, not TLRs

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15
Q

What 2 pathways are downstream of dectin-1 signalling?

A

inflammasome and NFkB

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16
Q

What does dectin-1 deficiency result in?

A

reduced IL-6 production and binding to candida–mucocutaneous fungal infections

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17
Q

What is required for NFkB activation by dectin-1?

A

CARD9

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18
Q

What does homozygous CARD9 mutation result in?

A

chronic mucocutaneous candidiasis

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19
Q

What cytokine is CARD9 required for production in response to beta-glucans?

A

TNFa

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20
Q

How is CARD9 invovled in T cell differentiation?

A

required for T cell Th17 differentiation

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21
Q

Deficiency in what TLR results in greater susceptibility to aspergillosis?

A

TLR4

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22
Q

What effect does plasminogen have aspergillosis defense?

A

directly binds to aspergillus conidia and decreases susceptibility

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23
Q

How are macrophage depleted mice affected with aspergillus fumigatus?

A

not any more susceptible

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24
Q

Which cells are most important in defense against invasive aspergillosis?

A

neutrophils - as without have no ability to clear the infection

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25
Q

What effect does NET production have on aspergillus?

A

traps fungus and stops from germinating

26
Q

How does the fungal morphogenesis affect T cell differentation?

A

different morphotypes are phagocytsed through different modalities by DCs which results in different mautration states

27
Q

What is the effect of coiling phagocytosis vs zipper-type on DC maturation?

A

coiling results in increased IL-12 production whereas zipper-type results in increased IL-4 and IL10 production

28
Q

What type of phagocytosis is used for single cell fungal morphology?

A

coiling

29
Q

What type of phagocytosis is used for hyphase forms of fungi?

A

zipper-type

30
Q

How does IFNy therapy aggect invasive fungal infection?

A

enhances clearance by down-regulating IL-10 and causing a burst of inflammatory cytokine expression

31
Q

What is required for NET formation?

A

ROS production

32
Q

What are the emerging possibilities in the treatment of fungal infections?

A

IFN-y injections and adoptive T cells therapy (generation of antifungal T cells from stem cells and then injected in patients)

33
Q

What are the main infections in patietns with CGD?

A

staph. and fungal infections

34
Q

What are the common aspergillus species in the environment?

A

aspergillus niger and aspergillus fumigatus

35
Q

What does the damage response framework describe?

A

that too weak or strong host responses to microbes can result in disease and death

36
Q

What patients have a much higher incidence of mould allergy?

A

asthmatics

37
Q

What are the 2 types of hypersensitivty reactions inovlved in ABPA?

A

type I and IV

38
Q

What type of hypersensitivty reaction is hypersensitivity pneumonitis?

A

type III and IV

39
Q

What is the main fungus invovled in allergy?

A

aspergillus

40
Q

Why is there a suggestion that some of the damage in allergic disease to aspergillosis is autoimmune?

A

there is cross-reactiivity of one of hte main aspergillus allergens with human cyclophylin

41
Q

What does ABPA stand for?

A

allergic bronchopulmonary aspergillosis

42
Q

What diseases predispose to ABPA?

A

CF and asthma

43
Q

What does hyphae formation allow the fungus to do?

A

germinate and proliferate

44
Q

What are the obligatory criteria for ABPA?

A

IgE >1000; positive skin prick or aspergillus specific IgE

45
Q

What are the radiological features of ABPA?

A

dilated bronchi with thick walls; ring/linear opacities; upper/central region prediliction; proximal bronchiectasis; lobar colllapse due to mucous impaction; fibrotic scarring

46
Q

What sign is seen on CT with ABPA?

A

hyper dense mucus sign

47
Q

What is the mainstya of treatment for ABPA?

A

steroids

48
Q

What can be used as a steroid sparing agent in ABPA?

A

itraconazole

49
Q

What is aspergillus rhinosinusitis associated with?

A

atopy and nasal polyposis

50
Q

What is seen on imaging with aspergillus rhinosinusitis?

A

obliterated sinuses with hypo-attenuated mucosa and enhancing material

51
Q

What are the 3 main cell wall components of funal species?

A

beta-glucans; chitin; mannans

52
Q

What is the function of galectin 3 in fungal infection?

A

allows aphgocytes to discriminate between pathogenic and non-pathogenic yeats through recognition of beta-mannosides

53
Q

What is the function of dectin-2 in fungal immunity?

A

high mannose structures that are common to many fungi and binds hyphal forms with higher affinity than yeast forms

54
Q

What type of fungus infection are dectin-2 deficient mice susceptible to?

A

C.albicans but not C.neoformans

55
Q

What other receptor does dectin-2 pair with to induce pro-inflammatory cytokines?

A

Fc receptor y chain

56
Q

What is the function of DC-SIGN?

A

recognises N-linked mannans, and directs mannosylated fungal antigens into the DC endocytic pathway promoting antigen processing and presentation to T cells

57
Q

What effect on fungal immunity does a polymorphism in TLR4 have ?

A

increased susceptibility to pulmonary aspergillosis and bloodstream candidiasis

58
Q

What fungal disease is a polymorphism in the promoter region of TLR9 associated with?

A

ABPA

59
Q

What allows fungal escape of C.albicans by dectin-1?

A

beta glucans are exposed in the bud scar of C.albicans yeasts but masked on hyphae

60
Q

How does P.jireveci evade immunosurveillance?

A

changes the expression of major surface glycoproteins

61
Q

What is the function of hte capsule of C.neoformans?

A

completely covers the fungal cell wall and prevetns recognition by PRRs and the induction of inflammation

62
Q

What might explain how c.neoformans establishes latency and spreads in the host wtihout triggering inflammation?

A

are able to escape from macrophages through an expulsive mechanism that does not kill the host cell and avoids inflammation