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99 Cards in this Set
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Approximately how many species of fungi are there? How many of these cause disease? |
*250,000 *180 in humans |
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What are some characteristics of fungi (be general) |
*Some unicellular (yeasts and molds) , others are multicellular (produce fruiting forms: mushrooms) *Cell wall is made of chitin *Movement primarily through growth + spore release *Feed on dead plant/animal material (saprophytic) |
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The fungal cell wall is mainly composed of ...
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*Polysaccharides |
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Which polysaccharides make up the fungal cell wall? |
*glucan - polymer of glucose residues *mannan - polymer of mannose residues |
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Fungal structure: What does the inner layer of the cell wall consist of? |
*Chitin |
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Fungal structure: What does the outer matrix of the cell wall consist of? |
*Glucans - B1-3-linked glucose residues Glycoproteins with either * serine/threonine O-linked mannose/galactose residues |
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Fungal structure: which 3 structures make up the fungal cell wall? |
1. inner layer of chitin microfibrils 2. outer matrix of glucans and glycoproteins 3. (some yeasts) outer polysaccharide capsule |
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What are the 3 possible morphologies of fungi? |
1. Yeasts - round unicellular 2. Moulds - filamentous, hypha, multicellular 3. Dimorphic fungi - exhibit morphology (1) or (2) depending on the environment |
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Describe the morphology of yeasts |
*Oval/round *unicellular *multiply by mitosis *some grow as short cylindrical pseudohyphae (Candida) |
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What are the 2 ways in which yeasts multiply? |
1. Symmetrical - binary fission (S.pombe) 2. Asymmetrical - budding (Candida, Cryptococcus) |
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Describe the morphology of moulds |
*hyphae = thin branching cylinders *multicellular *apical growth *layers of hyphae form fungal tissue e.g mushrooms |
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What are the 2 types of hypha? |
1. Septate: interconnected compartments (Aspergillus) 2. Aseptate: (Mucor) |
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What does 'apical growth' of hypha mean? |
*Mitosis only occurs at the tip *or at side branches behind the tip |
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What is a mycelium? |
An interwoven mass of hyphae compacted together |
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Dimorphic fungi differentiate appropriately to mould or yeast form depending on their environment. Describe this using Histoplasma as an example |
Histoplasma exists in different morphologies at different temperatures *filamentous mould at 22 degrees C in the environment differentiates to *unicellular yeast at 37 degrees C in the body of an animal |
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How do fungi reproduce? (note: not simply grow/divide) |
*produce spores |
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What are spores? |
*reproductive unit of fungi *tough light fungal cells |
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What 2 things are spores adapted for? |
1. Dispersal to new habitats 2. Survival in hostile environmental conditions |
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A given fungus can exists in 2 states of differentiation depending on the environmental conditions. What are these 2 states? |
*Asexual state - anamorph/mitotic/imperfect *Sexual state - telomorph/meiotic/perfect |
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In the asexual state, yeasts produce ... |
internal endospores |
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In the asexual state, some moulds produce |
*external spores on the outside of their hyphae - conidia others: *internal spores inside special sporangium hypha |
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What happens when a spore lands in a favourable habitat? |
*germinates into yeast/mould *multiples + colonises habitat |
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Which group of fungi always exist in an asexual state and are incapable of sexual reproduction? |
Deuteromycota (imperfect fungi) |
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Fungi exist mostly in a haploid or diploid state? |
Haploid |
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In the sexual state, a haploid fungus produces sexual structures such as ... ? |
*motile gametes - meiospores *specialised sexual hyphae |
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What are the stages in fungi sexual reproduction? |
1.Haploid sexual structures 2.Fusion 3.Diploid (reassortment + recombination occurs) 4.Meitotic reduction division 5.Haploid sexual spores |
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In hostile conditions, are you more likely to find asexual or sexual spores? Why? |
*Sexual spores *Tougher *Enable organism to survive until more favourable conditions arise in which they can germinate |
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Sexual spores that form internally, form within a structure called a ... |
ascus (tubular structure) |
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Sexual spores that form externally, form on a structure called a ... |
basidium (club-like structure) |
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Sexual spores that form externally, form as a thick-walled structure. What event does this follow? |
The fusion of specialised hyphae |
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Ascomycota form spores internally or externally? |
Internally |
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Basidiomycota form spores internally or externally? |
Externally |
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Zygomycota form spores internally or externally |
Externally |
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Deuteromycota (Imperfect fungi) form spores internally or externally? |
Externally |
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Basidomycota exist exclusively as which morphology of fungi? |
Yeast |
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Zygomycota exist exclusively as which morphology of fungi? |
Moulds |
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Imperfect fungi exist exclusively as which morphology of fungi?
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Dimorphic |
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Ascomycota form spores internally. Where do they form Sexual spores? |
*Sexual - ascus *Asexual - condia |
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Basidiomycota form spores externally on ... |
a basidium |
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Zygomycota form spores externally Where do they form Sexual spores? Where do they form Asexual spore? |
* Sexual - external fusion of hyphae * Asexual - in a sporangium |
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Imperfect fungi only form sexual spores. Where do they externally form these? |
Conidia |
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How do fungi obtain organic compounds from their environment? |
*secrete extracellular enzymes, digest food material *absorb simple soluble molecules through channels in fungal cell wall *use these preformed organic compounds for energy and carbon source |
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What is the key structural barrier to fungal entry? |
Intact epithelium *skin *moist mucosal surfaces *genital tract |
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What role do commensal bacterial flora play in the host defences against fungal infections? |
*inhibits multiplication of fungi on epithelial surface *also provide low-grade chemical warfare against foreign colonisation |
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Many of the Pattern Recognition Receptors which recognise fungi are ... |
Lectins - (protein with carbohydrate recognition domain that specifically binds defined carbohydrate structure) |
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Where are the PRR proteins which recognise fungal PAMPs found? |
*soluble in plasma - MBL *surface of dendritic cells, macrophages, neutrophils and some epithelial cells |
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Which effector cytokines produced by CD4+ T cells are important in the host response to fungal infection? |
*IL-17 *IL-22 |
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Increased susceptibility to fungal infections can occur as a result of specific defects in host defence. What are these defects? (4) |
1. Impaired fungal sensing 2. Impaired IL-17 immunity 3. Impaired neutrophil number or function 4. Impaired T cells & macrophage number or function |
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In which 2 ways fungal sensing be impaired? |
* Dectin-1 deficiency * CARD9 protein mutation |
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What causes Dectin-1 deficiency ? |
*point mutation = premature stop codon in extracellular carbohydrate recognition domain of the protein |
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What are the consequences of Dectin-1 deficiency? |
*homozygous individuals have blood mononuclear cells with reduced surface expression of Dectin-1 *stimulation with fungal B-glucan = reduced secretion of cytokines TNFa, IL-6 and IL-17 * = recognition of infection not communicated efficiently to rest of immune system |
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What is the importance of CARD9 in fungal sensing? |
CARD9 forms part of the intracellular signal transduction cascade downstream of Dectin-1 |
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How does a homozygous point mutation in CARD9 affect fungal sensing? |
*premature stop codon = reduced intracellular expression of CARD9 *Dectin-1 signalling pathway impaired |
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How does a reduction in Dectin-1 signalling affect fungal sensing? |
Leads to reduced numbers of Th17 CD4+ T celols |
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Which conditions are characteristic of impaired fungal sensing? |
*chronic fungal nail infections *mucosal candida infections |
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A selective susceptibility to chronic superficial Candida infection (in childhood) occurs as a result of ... |
* deficiency of the receptor for IL-17 * rare disorder: auto Ab against IL-17 and IL-22 |
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What is neutropenia? |
Severely reduced numbers of circulating neutrophils |
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In which inherited disorder does reduced function of neutrophils occur? Why? |
*Chronic Granulomatous Disease *mutation in gene coding NADPH oxidase system which usually generates superoxide to kill fungi |
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Impaired T cells and macrophage number/function predispose an individual to ... by... |
*Superficial AND deep infections by: *Yeasts (Candida, Pneumocystis, Cryptococcus) *Dimorphic fungi, enter as yeasts (Histoplasma) |
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How are fungal infections diagnosed? (3) |
1) in vitro culture form clinical sample -> Colony morphology 2) detection of fungal polysaccharide or fungal DNA in clinical sample 3) tissue biopsy + microscopy for morphological identification -> Single Fungi morphology |
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Which anti-fungal drugs target the fungal membrane? |
1.Polyenes - target ergosterol function
-> amphotericin, nyastatin 2. Azoles - target ergosterol synthesis -> clotrimazole, fluconazole, voriconazole 3. Allylamine - target ergosterol synthesis -> terbinafine |
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Which anti-fungal drugs target fungal microtubules? |
Friseofulvin |
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Which anti-fungal drugs target the fungal cell wall |
Echinocandin - target B-1,3 glucan synthesis -> caspofungin |
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What are the 3 main targets of specific anti-fungal drugs? |
1. Fungal membranes 2. Fungal microtubules (therefore cell division) 3. Fungal cell walls |
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In which ways and where can fungi cause disease in humans? (5) |
1. Presence of fungal toxins in food 2. Commensal infections (not harmful) 3. Superficial fungal infections of dead keratinized tissues 4. Subcutaneous fungal infections 5. Systemic (deep) fungal infections |
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Where is Candida Albicans found? |
*throat *gut *vagina |
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Are filamentous moulds part of normal human flora? |
No |
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Which types of fungi can cause superficial fungal infections? |
*dermatohype moulds (Microsporum, Trichohyton, Epidermophyton) * yeast Candida Albicans *yeast Malassezia furfur |
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How do chronic superficial fungal infections arise? |
*non-toxic fungal antigens induce local type IV hypersensitivity responses *activation of host CD4+ T cells , secrete cytokines - +++ skin cell proliferation = flaky skin -itching = scratching = 2ndary bacterial infection |
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What is the result of superficial Candida albicans infection? |
disfiguring chronic finger nail infection |
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What is the result of superficial Malassezia furfur infection? |
pityriasis versicolour (blotchy skin rash, doesn't tan) |
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How are Superficial fungal infections treated? |
*Topical cremes: Clotrimazole, Terbinafine *Oral Terbinafine |
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How do subcutaenous fungal infections arise |
*low virulence saprotrophs in soil/vegetation *injury occurs *implantation of the organisms through the skin *therefore often occupational disease of farmers, gardners, vets |
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What are the characteristics of a subcutaneous fungal infection? |
*develops slowly *but might spread up limb via lymphatics |
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What are the 2 mains types of systemic fungal infections? |
1. Systemic pathogens 2. Systemic Opportunists |
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What are the characteristics of a systemic pathogen that causes deep infection? |
*High virulence *Infects both healthy and immunocompromised people *Route of entry is via lungs (spores) *Asymptomatic infection of macrophages |
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What are the characteristics of a systemic opportunists that cause deep infection? |
*Low virulence *Infect only immunocompromised people *Route of entry via lung, gut, i.v lines *No infection of macrophages |
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Which factors determine the consequences of infection by systemic pathogen? |
*The strain *infectious dose *resistance of the host |
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What does the temperature-sensitive dimorphism in Histoplasma regulate in order to induce a pattern of gene expression? |
DRK1 and RYP1 kinases = equips yeast for life in mammalian macrophages |
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How does histoplasma evade the host immune system? |
* expresses a-1,3-glucan not recognised by host PRRs *expresses hsp60 binds CD11/CD18 on macrophages |
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How does histoplasma facilitate growth within macrophage vacuoles? |
*expresses secreted protease-resistant calcium binding protein |
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How is persistent intracellular infection controlled? |
*T cell response *activates macrophages = granuloma formation |
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What determines the consequences of infection with a systemic opportunist? |
Seriousness of infection is related to the severity of the underlying host defect |
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What is Candida albicans? |
*commensal *yeast *usually found on moist mucosal surfaces *usually restrained by host defences and bacterial competition |
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What is Pneumocystis jirovecii? |
*yeast *obligate parasite of humans *cannot be cultured in vivo *almost universal asymptomatic infection in early life *reaquisition of airborne form of those with impaired T cell immunity causes lung disease |
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What is Pneumocystis pneumonia (PCP)? |
*diffuse inflammation of lung alveoli *clusters of oval fungal organisms in airspaces *injury to alveolar epithelial cells *alveoli fill with protein rich foamy exudate *impairment of gas diffusion = arterial hypoxaemia |
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How is Pneumocystis penumonia (PCP) treated? |
*high dose Co-trimoxazole (inhibits folic acid synth) *treatment with corticosteroids (reduce inflammatory response) |
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In PCP what causes the inflammation? |
Inflammation is an innate response to the fungal polysaccharides released by dying organisms. |
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What is Cryptococcus neoformans? |
*yeast *thick polysaccaride capsule *infection by inhalation *spreads from lung to circulation to CNS |
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What are the 2 types of infection with Cryptococcus neoformans causes? |
1. Pneumonia (rare) - normal or immunosuppressed patients 2. Meningo-encephalitis - T cell immunodeficient patients |
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What are the symptoms of meningo-encephalitis? |
*worsening headache *fever *confusion *excessive accumulation of CSF (hydroephalus) Survivors may have persistent neurological disability, 20% fatality rate |
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How is Cryptococcus neoformans infection treated? |
AMphotericin + Flucytosine followed by long term high-dose Fluconazole |
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How is Candida albicans infection treated? |
Fluconazole or Caspofungin |
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What is Aspergillus fumigatus |
* a mould *environmental *abundant air-borne spores |
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What are the 3 types of infection Aspergillus fumigatus causes? |
1. Airway colonisation - asthma 2. Aspergilloma (mass of hyphae) - in pre-existing lung cavity e.g TB survivor 3. Invasive infection of lung or perinasal sinuses, spread to blood vessels, disseminates - severe neutropenia |
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How is Aspergillus fumigatus infection treated? |
*Amphotericin or Voriconazole *Surgery if possible |
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What is Mucor? |
*A mould * environmental * acquired usually by inhalation of air-borne spores * acquired occasionally by direct contamination of wounds |
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What type of infection does Mucor cause? |
Mucotmycosis (rare but very serious) - very high fatality rate when mould aggressively invades paranasal sinuses of lungs Usually in poorly controlled diabtetes or leukemia |
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How is Mucor infection treated? |
*Urgent surgery to remove dead tissue *I.V AMphotericin |