• Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

Card Range To Study

through

image

Play button

image

Play button

image

Progress

1/99

Click to flip

Use LEFT and RIGHT arrow keys to navigate between flashcards;

Use UP and DOWN arrow keys to flip the card;

H to show hint;

A reads text to speech;

99 Cards in this Set

  • Front
  • Back

Approximately how many species of fungi are there? How many of these cause disease?

*250,000


*180 in humans

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)

The fungal cell wall is mainly composed of ...

*Polysaccharides

Which polysaccharides make up the fungal cell wall?

*glucan - polymer of glucose residues


*mannan - polymer of mannose residues

Fungal structure: What does the inner layer of the cell wall consist of?

*Chitin
*long, straight chains of B-1-4-linked N-acetylglucosamine (NAG) residues

Fungal structure: What does the outer matrix of the cell wall consist of?

*Glucans - B1-3-linked glucose residues




Glycoproteins with either
* asparagine N-linked mannose/galactose residues


* serine/threonine O-linked mannose/galactose residues



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

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

Describe the morphology of yeasts

*Oval/round


*unicellular


*multiply by mitosis


*some grow as short cylindrical pseudohyphae (Candida)

What are the 2 ways in which yeasts multiply?

1. Symmetrical - binary fission (S.pombe)


2. Asymmetrical - budding (Candida, Cryptococcus)

Describe the morphology of moulds

*hyphae = thin branching cylinders


*multicellular


*apical growth
*hyphae can form interwoven mass: mycelium


*layers of hyphae form fungal tissue e.g mushrooms

What are the 2 types of hypha?

1. Septate: interconnected compartments (Aspergillus)


2. Aseptate: (Mucor)

What does 'apical growth' of hypha mean?

*Mitosis only occurs at the tip


*or at side branches behind the tip

What is a mycelium?

An interwoven mass of hyphae compacted together

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

How do fungi reproduce? (note: not simply grow/divide)

*produce spores

What are spores?

*reproductive unit of fungi


*tough light fungal cells



What 2 things are spores adapted for?

1. Dispersal to new habitats


2. Survival in hostile environmental conditions

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

In the asexual state, yeasts produce ...

internal endospores

In the asexual state, some moulds produce

*external spores on the outside of their hyphae - conidia


others:


*internal spores inside special sporangium hypha

What happens when a spore lands in a favourable habitat?

*germinates into yeast/mould


*multiples + colonises habitat

Which group of fungi always exist in an asexual state and are incapable of sexual reproduction?

Deuteromycota (imperfect fungi)

Fungi exist mostly in a haploid or diploid state?

Haploid

In the sexual state, a haploid fungus produces sexual structures such as ... ?

*motile gametes - meiospores


*specialised sexual hyphae

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

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

Sexual spores that form internally, form within a structure called a ...

ascus




(tubular structure)

Sexual spores that form externally, form on a structure called a ...

basidium


(club-like structure)



Sexual spores that form externally, form as a thick-walled structure. What event does this follow?

The fusion of specialised hyphae

Ascomycota form spores internally or externally?

Internally

Basidiomycota form spores internally or externally?

Externally

Zygomycota form spores internally or externally

Externally

Deuteromycota (Imperfect fungi) form spores internally or externally?

Externally

Basidomycota exist exclusively as which morphology of fungi?

Yeast

Zygomycota exist exclusively as which morphology of fungi?

Moulds

Imperfect fungi exist exclusively as which morphology of fungi?

Dimorphic

Ascomycota form spores internally.


Where do they form Sexual spores?
Where do they form Asexual spore?

*Sexual - ascus


*Asexual - condia

Basidiomycota form spores externally on ...

a basidium

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

Imperfect fungi only form sexual spores. Where do they externally form these?

Conidia

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

What is the key structural barrier to fungal entry?

Intact epithelium


*skin


*moist mucosal surfaces
*intestine


*genital tract

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

Many of the Pattern Recognition Receptors which recognise fungi are ...

Lectins - (protein with carbohydrate recognition domain that specifically binds defined carbohydrate structure)

Where are the PRR proteins which recognise fungal PAMPs found?

*soluble in plasma - MBL


*surface of dendritic cells, macrophages, neutrophils and some epithelial cells

Which effector cytokines produced by CD4+ T cells are important in the host response to fungal infection?

*IL-17


*IL-22

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

In which 2 ways fungal sensing be impaired?

* Dectin-1 deficiency


* CARD9 protein mutation

What causes Dectin-1 deficiency ?

*point mutation = premature stop codon in extracellular carbohydrate recognition domain of the protein



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

What is the importance of CARD9 in fungal sensing?

CARD9 forms part of the intracellular signal transduction cascade downstream of Dectin-1

How does a homozygous point mutation in CARD9 affect fungal sensing?

*premature stop codon = reduced intracellular expression of CARD9


*Dectin-1 signalling pathway impaired

How does a reduction in Dectin-1 signalling affect fungal sensing?

Leads to reduced numbers of Th17 CD4+ T celols

Which conditions are characteristic of impaired fungal sensing?

*chronic fungal nail infections


*mucosal candida infections

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

What is neutropenia?

Severely reduced numbers of circulating neutrophils

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

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)

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

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


Which anti-fungal drugs target fungal microtubules?

Friseofulvin

Which anti-fungal drugs target the fungal cell wall

Echinocandin - target B-1,3 glucan synthesis


-> caspofungin

What are the 3 main targets of specific anti-fungal drugs?

1. Fungal membranes


2. Fungal microtubules (therefore cell division)


3. Fungal cell walls

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

Where is Candida Albicans found?

*throat


*gut


*vagina

Are filamentous moulds part of normal human flora?

No

Which types of fungi can cause superficial fungal infections?

*dermatohype moulds (Microsporum, Trichohyton, Epidermophyton)


* yeast Candida Albicans


*yeast Malassezia furfur

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

What is the result of superficial Candida albicans infection?

disfiguring chronic finger nail infection

What is the result of superficial Malassezia furfur infection?

pityriasis versicolour (blotchy skin rash, doesn't tan)

How are Superficial fungal infections treated?

*Topical cremes: Clotrimazole, Terbinafine


*Oral Terbinafine

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

What are the characteristics of a subcutaneous fungal infection?

*develops slowly
*remains localised: subcutaneous nodule lump


*but might spread up limb via lymphatics

What are the 2 mains types of systemic fungal infections?

1. Systemic pathogens


2. Systemic Opportunists

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

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

Which factors determine the consequences of infection by systemic pathogen?

*The strain


*infectious dose


*resistance of the host



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

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

How does histoplasma facilitate growth within macrophage vacuoles?

*expresses secreted protease-resistant calcium binding protein

How is persistent intracellular infection controlled?

*T cell response


*activates macrophages = granuloma formation





What determines the consequences of infection with a systemic opportunist?

Seriousness of infection is related to the severity of the underlying host defect

What is Candida albicans?

*commensal


*yeast


*usually found on moist mucosal surfaces


*usually restrained by host defences and bacterial competition

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

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

How is Pneumocystis penumonia (PCP) treated?

*high dose Co-trimoxazole (inhibits folic acid synth)


*treatment with corticosteroids (reduce inflammatory response)

In PCP what causes the inflammation?

Inflammation is an innate response to the fungal polysaccharides released by dying organisms.

What is Cryptococcus neoformans?



*yeast
*abundant in bird droppings


*thick polysaccaride capsule


*infection by inhalation


*spreads from lung to circulation to CNS





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

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

How is Cryptococcus neoformans infection treated?

AMphotericin + Flucytosine followed by long term high-dose Fluconazole



How is Candida albicans infection treated?

Fluconazole or Caspofungin

What is Aspergillus fumigatus



* a mould


*environmental


*abundant air-borne spores

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

How is Aspergillus fumigatus infection treated?

*Amphotericin or Voriconazole


*Surgery if possible

What is Mucor?

*A mould


* environmental


* acquired usually by inhalation of air-borne spores


* acquired occasionally by direct contamination of wounds

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

How is Mucor infection treated?

*Urgent surgery to remove dead tissue


*I.V AMphotericin