IMMUNE 228 Fungal Disease Flashcards
Mycoses
Fungi capable of causing infections in humans
Mycotoxins
Produces by mycoses cause disease - mycotoxicoses
Fungal Structure
Eukaryotic - uni/multicellular
Cell wall and plasma membranes containing ergosterol (cholesterol equivalent)
Pseudohyphae
Unicellular fungal cells forming a long chain
hyphae
Long thin extensions of filamentous multi-cellular fungi
Mycelium
Tangles of hyphae
Describe yeasts and give some examples
Unicellular fungal organisms that lack mycelia and asexually reproduce by budding. Can form pseudohyphae
e.g. malassaezia furfur, candida and cryptococcus
Describe mould/filamentous fungi and give some examples
Multicellular fungal organisms that grow as a dense mass of hyphae (mycelium)
e.g. microsporum, epidermophyton, tricophyton (all cause dermatophytosis=tinea) or aspergillus
Describe dimorphic fungi and give examples
Grow as filamentous or yeast depending on conditions they’re exposed to
e.g histoplasmosa capitulum
blastomyces or pneumocystis (PCP)
What are prions?
Infections glycoprotein particles that cause fatal neurological conditions in humans
What are protozoa? Give examples
Unicellular eukaryotes - larger than bacteria but smaller than helminths or arthropods
e.g. malaria (plasmodium) , african sleeping sickness or chagas disease (trypanosome) and giardiasis
Helminths and give examples
Multicellular eukaryotes - parasitic worms
e.g. schistosomiasis, enterobiasis, elephantiasis
Arthropods
Largest multicellular eukaryote - e.g ticks, mosquitos . Act directly or indirectly (as a vector)
Describe dermatophytosis infections
Fungi digest keratin by their keratinases, they are resistant to cycloheximide
Infection in classified anatomicaly e.g. tinea: corpis, pedis, cruris etc..
Most commonly in immunocompromised hosts
Describe the pathogenecity of a superficial candidiasis infection?
Change from yeast to a pseudohyphal form which adheres to epithelial cells producing enzymes to break down the tissue
Who gets invasive candidiasis infections?
Those with predisposing factors e.g. neutropenia, antibiotic use, indwelling lines and abdominal surgery
What are the two types of aspergillosus infection where is aspergillous found?
Found globally in soil and other organic matter
Invasive and non invasive
Describe invasive aspergillosus
Often immunocompromised host who inhales the fungal spores. There is invasion of blood vessels and tissues within and outside of the lung.
CXR there are multi-focal opacities (halo sign) which progresses to consolidation
Multiple lung infarcts due to blockages of vessels
Describe non-invasive aspergillosus
Due to heavy exposure in normal individuals and is a hyper-sensitivity pneumonitis
Type 3 and 4 immune hypersensitivity reaction
Pc: dyspnoea, fever, flu like symptoms, relieved when exposure stops
e.g. pigeons, farmers, humidifiers, brewers and cheese
Describe ABPA
Allergic bronchopulmonary aspergillosus due to low exposure in individuals with asthma or CF
There is colonisation of the mucus plugs = further type 3 and 4 hypersensitivity reaction (alongside asthma type 1)
Fungal hyphae will be found in mucus plug and there will be exacerbation of the condition
What is a type 3 hypersensitivity reaction?
formation of immune complexes due to pathogen
e.g. ab’s binding to proteins from the fungus
= complement activation –> inflammation and tissue damage
What is a type 4 hypersensitivity reaction?
Immune mediated - activation of lymphocytes and macrophages = granuloma formation = bronchiectasis and fibrosis
What investigations would be done for ABPA?
sputum -look for hyphae, check blood: eosinophillia, raised IgE, positive ab’s ; bronchi-alveolar lavage
How would you manage ABPA?
Cannot have long term anti-fungals so would have long term steroids and optimally manage asthma/CF
possible physio and bronchoscopy to remove mucus plugs
Mycetoma
Colonisation of the cavities with fungus in existing cavitating lung disease e.g. old TB, abscess, bronchiectasis and chronic interstitial lung disease
What causes haemoptysis in mycetoma/fungal lung disease?
Release of oxalic acid by hyphae = blood vessel erosion and haemoptysis
How would a mycetoma look histologically?
Pink necrotic centre of dead cells and debris with a rim of active hyphae
Which anti-fungals inhibit membrane synthesis?
The azoles, echinocandins and allylamines
Which anti-fungals inhibit membrane function?
polyenes
Which anti-fungal inhibits nucleic acid synthesis?
Flucocytosine
Which anti-fungal inhibits mitosis ?
Griseofulvin
Give some examples of -azole antifungals?
Imidazoles - ketoconazole and topical imidazoles e.g. clotrimazole
Triazoles - fluconazole, voricanozole and itraconazole
Give an example of an echinocandin?
caspofungin
Give an example of an allylamine?
terbinafine
Give some examples of polyenes?
amphotericin and nystatin
Describe the MoA of -azole antifungals?
Inhibit cytochrome p450 of fungus = decreased membrane ergosterol therefore increase permeability
What do the echinocandin anti-fungals inhibit?
beta-glucan synthase = weaker wall due to decreased glucan
What do the allylamines inhibit?
Squalene epioxidase therefore decreased ergosterol
What is the moa of polyenes?
Bind to ergosterol and form pores = cation leakage
