23 Pathogenicity-fungi immune evasion Flashcards
(104 cards)
1
Q
what is the most common type of superficial fungal infections
A
Dermatophytosis
2
Q
where does dermatophytosis infect
A
- Stratum corneum (upper skin surface)
- Nails
- Hair (scalp)
3
Q
what does dermatophytes infect
A
humans
animals
saprophyte in soil
4
Q
what is anthropophilic
A
infects humans
5
Q
what is zoophilic
A
infects animals
6
Q
what is geophilic
A
generally saprophyte in soil
7
Q
what is the Stratum corneum
A
- Epidermal layer of dead cells
- Rich in keratin
- Protects underlying tissues
8
Q
what increases risk of zoonotic infections
A
Direct contact with these infected animals
9
Q
what do antropophilic fungi cause
A
generally chronic infections with low inflammation
10
Q
what do zoonotic infections usually come with
A
accompanied by inflammatory host response
11
Q
what do dermatophytic fungi require
A
ability to degrade keratin staining
12
Q
what does keratin form
A
alpha helical structure and builds filaments
13
Q
what is keratin
A
protein
14
Q
how flexible is keratin
A
Amount of cysteine residues determine the rigidity of keratin fibrils
15
Q
what is cystine
A
Disulfide bond from two cysteines = cystine
16
Q
what are dermatophytes rich in
A
proteases
17
Q
what do dermatophytes make from cysteine degradation
A
sulfite
18
Q
what happens when sulfite is secreted
A
reduces cysteine bridges (cystines)
= Proteins become accessible for degradation by proteases
19
Q
how are fungal infections diagnosed
A
Cultivation of fungi
Staining and visualisation of hyphae in infected tissues
Diagnostic PCR
20
Q
how are fungal infections treated - superficial skin
A
topical application of azoles or terbinafine
21
Q
how are fungal infections treated - scalp infections
A
azoles, sometimes systemic application
22
Q
how are fungal infections treated - nail infection
A
Topical + systemic treatment and nail removal to be considered
23
Q
how long does therapy last for fungal infection
A
takes between 2 and 48 weeks of treatment, depending where it is located
24
Q
what are major risk factors in fungal infection
A
- Immunosuppressive regimen (graft versus host disease, leukaemia)
- Chronic granulomatous disease (CGD)
- Other inborne immunodeficiency
- AIDS (HIV infection)
25
what is Histoplasma capsulatum
Environmental dimorphic fungus
26
where is Histoplasma capsulatum found
Strongly enriched in droppings of birds and bats
27
what does Histoplasma capsulatum infect
immunocompromised and healthy individuals
28
how does Histoplasma capsulatum avoid immune mechanisms
- Immune cells generally detect β-glucans in the fungal cell wall via Dectin-1
- Dectin-1-mediated phagocytosis elicits an inflammatory immune response
- α-glucan is not immune stimulatory
- α-glucan overlays the β-glucan layer
29
what does Histoplasma capsulatum acquire
essential nutrients from the host and replicates within macrophages
30
Histoplasma capsulatum and antimicrobial defense molecules
Detoxifies antimicrobial defense molecules
31
how does condida get into body
uptake by inhalation (lung alveoli)
32
what happens once entered cell
Adherence to macrophage β-integrins
33
what are CD18
complement receptors
34
what blocks phagocytosis
Antibodies against HSP60
35
when are the first symptoms of Histoplasmosis
about two weeks after conidia inhalation
36
what are the symptoms at start
Silent manifestation (no symptoms)
37
what happens in the acute phase of Histoplasmosis
non-specific respiratory symptoms (cough or flu-like)
38
what happens in the chronic phase of histoplasmosis
similar symptoms as tuberculosis
39
what can Histoplasmosis
| lead to in immunocompromised patients
especially AIDS = reduced T-cells
40
what is the problem with HIV and macrophage function
HIV reduces number of CD4+ cells that activate CD8+ killer cells
CD8+ killer cells are essential to recognise and kill infected macrophages
41
what is the therapy for Histoplasmosis
Primary therapy with amphotericin B
| Secondary therapy with azoles (may need one year for clearance of infection)
42
what is PCP
Pneumocystis pneumonia
43
what is throphozoit
Pneumocystis trophic form
44
what is cyst
Pneumocystis cyst form
45
what is special about Pneumocystis
species are specialised towards their host
46
what is the pneumocystis life cycle
```
Trophic form (asexual) multiplies by binary fission
Cysts result from sexual crossing, meiosis and mitosis
```
47
what are the cysts cell walls like
thick cell wall mainly made of β-glucans, chitin, mannoproteins
48
what do β(1,3/1,6)-glucans cause in cysts cell wall
severe inflammatory response by immune recognition
49
what us the trophic cell wall like
without β-glucans and very thin cell wall
50
what is the flexibility of trophic cell wall
Flexible in the cell wall (as no beta glucan)
51
what does trophic express
integrin like molecule PcInt1
52
what does integrin interact with
extracellular matrix of epithelial cells (fibronectin and vitronectin)
53
what is reduced in trophic cell wall
Expression of surfactant phospholipids by epithelial cells reduced
54
why is AIDS cause a major problem to Pneumocystic infection
Implies major role of CD4+ cells in clearance, but mainly through cytokine response
CD8 T cell depletion does not increase risk for infection
Adaptive B-cell response important for clearance
Macrophages and neutrophils phagocytose and inactivate cysts and trophozoits
55
what causes major disease transmission in Pneumocystis
cysts
56
what does Pneumocystis not produce (unlike other fungi)
ergosterol
57
what are the problems with treating Pneumocystis
- Natural resistance against azoles
- Low sensitivity against amphotericin B
- don’t have beta glucan = no trophozoits
58
what is important for transmission control in Pneumocystis
Echinocandins active against cysts, but need co-application of sterols
59
what is Cryptococcus neoformans divided into
four serotypes A, B, C, D
60
who are the individuals at risk to Cryptococcus neoformans
mainly infects immunocompromised individuals
- Highest risk for HIV infected patients with AIDS
- Transplant recipients identified as emerging group at risk
61
what does Asexual Cryptococcus form
yeast cells
62
how do Asexual Cryptococcus infect
by inhalation of
- Blastoconidia
- Desiccated spores
63
what causes Cryptococcosis
released from bird droppings
64
why does cryptococcosis not infect birds
birds don’t get infected as their body temperature is too high – cannot proliferate in the tissues, but can survive and proliferate in intestine – in bird droppings
65
what is the major virulence factors of cryptococcus
Polysaccharide capsule
66
what is the polysaccharide capsule made of
galactoxylomannan (GXM)
67
what does the polysaccharide capsule do
Protects from cell-wall recognition and immune activation
68
what is melanisation in crypotococcus
Activation of host diphenolic compounds
69
what does melanisation stabilise
fungal cell wall
70
what does melanisation reduce
susceptibility to antifungal agents
71
what can melanin scavenge
reactive oxygen species
72
what can some cryptococcus cells form
titan/giant cells
73
when are titan cells made
formation is stimulated when both mating partners cause infection
74
what cant occur to titan cells
cannot be phagocytosed – surrounded by large capsule (cannot be opsonised)
Promotes survival within the host
75
what is the the main disease from cryptococcus
acute meningitis
76
what can occur in cryptococcus infections
Latent infection frequent (no complete clearance) = Reactivation possible
77
dendritic cell role in cryptococcus clearance
phagocytose Cryptococcus and present antigens to T-cells
78
adaptive T cell role in cryptococcus clearance
Adaptive T-cell response from CD4+ and CD8 cells play major role in clearance
- Low CD4+ counts in HIV patients major risk factor
79
what is the therapy for acute meningitis
Initial therapy with combination of two
Maintenance therapy with another
Echinocandins are not effective
80
what are Aspergillus species
environmental saprophytes
81
where are Aspergillus species
common in soil and on decaying organic matter
82
where is Aspergillus terreus
Common in soil and on decaying organic matter
83
what is Aspergillus terreus problem
Natural Amphotericin B resistance
84
what is frequent in Aspergillus terreus
dissemination
85
what is the thermotolerance of Aspergillus terreus
Moderately thermotolerant (42°C)
86
where is Aspergillus fumigatus
Common in soil and on decaying organic matter
87
what is the thermotolerance of Aspergillus fumigatus
Highly thermotolerant (55°C)
88
what is dissemination of A. terreus interaction with DC
Activation of DCs leads to transmigration to lymph nodes
Present antigens mainly to T-cells (and B-cells)
Mediators between innate and the adaptive immune response
89
Phagocytosis of A. fumigatus and A. terreus by DCs
DCs phagocytose A. fumigatus faster than A. terreus
A. fumigatus escapes from DCs
A. terreus mainly persists
90
what is the germination of A. fumigatus like
a very low nutrient threshold
91
what is the germination of A. terreus like
speed is dependent on nutrient availability
92
what is the survival of A. fumigatus conidia after DC phagocytosis
inactivated
93
what is the survival of A. terreus conidia after DC phagocytosis
remain viable
94
what is the survival in presence of antimycotics and DCs - A. fumigatus conidia
not protected from antifungals
95
what is the Survival in presence of antimycotics and DCs - A. terreus conidia
Persistent A. terreus conidia are protected
96
does A. fumingatus cause DC activation
Viable A. fumigatus candida trigger DC activation and transmigration
97
does A. terreus cause DC activation
do not elicit DC activation
98
does A. fumingatus cause cytokine production by DC
trigger an inflammatory immune response
99
does A. terreus cause cytokine production by DC
no
100
where can A. terreus conidia persist
macrophages and DCs and TNF-α stimulated DCs
101
what does TNF-alpha stimulate
transmigration of A. terreus infected DCs
102
what is a suitable vehicle for A. terreus
DCs
103
A. fumigatus infections strategies
rapid acute pulmonary disease
- A. fumigatus follows a “germinate and escape” strategy
- Rapid progression is life-threatening
104
A. terreus infections strategy
“sit and wait” strategy
- A. terreus conidia can hitchhike innate immune cells for dissemination
- Disseminated infection has mortality rates > 90%
