IMMUNE 228 Fungal Disease

Question 1

Mycoses

Answer 1

Fungi capable of causing infections in humans

Question 2

Mycotoxins

Answer 2

Produces by mycoses cause disease - mycotoxicoses

Question 3

Fungal Structure

Answer 3

Eukaryotic - uni/multicellular

Cell wall and plasma membranes containing ergosterol (cholesterol equivalent)

Question 4

Pseudohyphae

Answer 4

Unicellular fungal cells forming a long chain

Question 5

hyphae

Answer 5

Long thin extensions of filamentous multi-cellular fungi

Question 6

Mycelium

Answer 6

Tangles of hyphae

Question 7

Describe yeasts and give some examples

Answer 7

Unicellular fungal organisms that lack mycelia and asexually reproduce by budding. Can form pseudohyphae
e.g. malassaezia furfur, candida and cryptococcus

Question 8

Describe mould/filamentous fungi and give some examples

Answer 8

Multicellular fungal organisms that grow as a dense mass of hyphae (mycelium)
e.g. microsporum, epidermophyton, tricophyton (all cause dermatophytosis=tinea) or aspergillus

Question 9

Describe dimorphic fungi and give examples

Answer 9

Grow as filamentous or yeast depending on conditions they’re exposed to
e.g histoplasmosa capitulum
blastomyces or pneumocystis (PCP)

Question 10

What are prions?

Answer 10

Infections glycoprotein particles that cause fatal neurological conditions in humans

Question 11

What are protozoa? Give examples

Answer 11

Unicellular eukaryotes - larger than bacteria but smaller than helminths or arthropods
e.g. malaria (plasmodium) , african sleeping sickness or chagas disease (trypanosome) and giardiasis

Question 12

Helminths and give examples

Answer 12

Multicellular eukaryotes - parasitic worms

e.g. schistosomiasis, enterobiasis, elephantiasis

Question 13

Arthropods

Answer 13

Largest multicellular eukaryote - e.g ticks, mosquitos . Act directly or indirectly (as a vector)

Question 14

Describe dermatophytosis infections

Answer 14

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

Question 15

Describe the pathogenecity of a superficial candidiasis infection?

Answer 15

Change from yeast to a pseudohyphal form which adheres to epithelial cells producing enzymes to break down the tissue

Question 16

Who gets invasive candidiasis infections?

Answer 16

Those with predisposing factors e.g. neutropenia, antibiotic use, indwelling lines and abdominal surgery

Question 17

What are the two types of aspergillosus infection where is aspergillous found?

Answer 17

Found globally in soil and other organic matter

Invasive and non invasive

Question 18

Describe invasive aspergillosus

Answer 18

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

Question 19

Describe non-invasive aspergillosus

Answer 19

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

Question 20

Describe ABPA

Answer 20

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

Question 21

What is a type 3 hypersensitivity reaction?

Answer 21

formation of immune complexes due to pathogen
e.g. ab’s binding to proteins from the fungus
= complement activation –> inflammation and tissue damage

Question 22

What is a type 4 hypersensitivity reaction?

Answer 22

Immune mediated - activation of lymphocytes and macrophages = granuloma formation = bronchiectasis and fibrosis

Question 23

What investigations would be done for ABPA?

Answer 23

sputum -look for hyphae, check blood: eosinophillia, raised IgE, positive ab’s ; bronchi-alveolar lavage

Question 24

How would you manage ABPA?

Answer 24

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

Question 25

Mycetoma

Answer 25

Colonisation of the cavities with fungus in existing cavitating lung disease e.g. old TB, abscess, bronchiectasis and chronic interstitial lung disease

Question 26

What causes haemoptysis in mycetoma/fungal lung disease?

Answer 26

Release of oxalic acid by hyphae = blood vessel erosion and haemoptysis

Question 27

How would a mycetoma look histologically?

Answer 27

Pink necrotic centre of dead cells and debris with a rim of active hyphae

Question 28

Which anti-fungals inhibit membrane synthesis?

Answer 28

The azoles, echinocandins and allylamines

Question 29

Which anti-fungals inhibit membrane function?

Answer 29

polyenes

Question 30

Which anti-fungal inhibits nucleic acid synthesis?

Answer 30

Flucocytosine

Question 31

Which anti-fungal inhibits mitosis ?

Answer 31

Griseofulvin

Question 32

Give some examples of -azole antifungals?

Answer 32

Imidazoles - ketoconazole and topical imidazoles e.g. clotrimazole
Triazoles - fluconazole, voricanozole and itraconazole

Question 33

Give an example of an echinocandin?

Answer 33

caspofungin

Question 34

Give an example of an allylamine?

Answer 34

terbinafine

Question 35

Give some examples of polyenes?

Answer 35

amphotericin and nystatin

Question 36

Describe the MoA of -azole antifungals?

Answer 36

Inhibit cytochrome p450 of fungus = decreased membrane ergosterol therefore increase permeability

Question 37

What do the echinocandin anti-fungals inhibit?

Answer 37

beta-glucan synthase = weaker wall due to decreased glucan

Question 38

What do the allylamines inhibit?

Answer 38

Squalene epioxidase therefore decreased ergosterol

Question 39

What is the moa of polyenes?

Answer 39

Bind to ergosterol and form pores = cation leakage