Immunity to fungal infections

Question 1

Describe the morphogenesis of candida

Answer 1

Candida show dimorphism (two forms, yeast buds or hyphae) which allows for invasion

Question 2

Describe the morphogenesis of Crytpococcus

Answer 2

Forms a capsule to evade phagocytosis

Question 3

Describe the morphogenesis of Aspergillus

Answer 3

invades tissues as hyphae

Question 4

How do aspergillius species infiltrate the body

Answer 4

species inhaled as conidia

Following spore dispersion, the infection cycle consists of germination, hyphal elongation and branching in order to form a mass of hyphae

Question 5

How are mycoses classified by level of tissue affected

Answer 5

Superficial. Cutaneous and subcutaneous (affect primarily the skin and subcutaneous tissues)
Systemic (deep infection which spreads around the body)

Question 6

Compare primary/true pathogens to opportunistic pathogens

Answer 6

Primary/true pathogens can establish infection in non-immunocomprimised hosts

Opportunistic pathogens require some sort of immunocomprimised hosts to it order to establish infection. These include:
• Aspergillus species
• Candida species
• Cryptococcus species

Question 7

What does yeast mean

Answer 7

describes single-celled fungal morphotypes such as those exhibited by C. albicans and C. neoformans

Question 8

What is the difference between C. neoformans and candida albicans

Answer 8

C. neoformans - encapsulated yeast, which has a thick polysaccharide cell wall referred to as the capsule

Candida albicans - a budding yeast which can differentiate into elongated pseudohyphal (lacking true cell walls) and/or hyphal forms in response to environmental signals such as pH, nutrient limitation and exposure to serum

Question 9

Describe pseudohyphal cells

Answer 9

lack the dividing partitions known as septa found in true hyphae

Question 10

What is a mycelium

Answer 10

A fungal colony composed of multiple branches hyphae

Question 11

Give examples of how fungi infects humans

Answer 11

Attachment and invasion of damaged skin/epithelia e.g. candida
Inhalation and deposition in the respiratory tract e.g. aspergillius
Direct inoculation into deep tissues e.g. Candida, asperlligus pathos

Question 12

What are the risk factors for deep infection

Answer 12

Chemotherapy
Surgery
Catheterisation
AIDS

Question 13

Explain how candida species are able to infiltrate into the body

Answer 13

They are opportunistic commensals of the gut, oral and genitourinary tracts.
Disseminated candidiasis often originates at a GI site by entering the
vasculature via epithelial microvilli.

Question 14

Which immune defence mechanism in its absence allows aspergillum species to infect

Answer 14

Normally, ciliary clearance and pulmonary polymorphonuclear leukocytes protect effectively against infection

Absence - germinate and go on to produce a lesion in the lung

Question 15

Why is it difficult to develop vaccines against fungal infections

Answer 15

immune response varies according to site of infection, species and morphotype

Question 16

What is the first line of defence against fungal pathogens

Answer 16

physical

On the skin, or oral/pulmonary/gastrointestinal mucosa

Question 17

What is the role of pathogens in defence against fungal pathogens

Answer 17

If this first line of defence is breached, and infiltration/fungal colonization occurs, phagocytes play an essential role.
Phagocytosis results in fungal killing, as well as increased exposure of fungal antigens to APC.

Question 18

Which cells are involved the destruction of fungi (normal) by innate defence mechanisms and how long does it take

Answer 18

Mediated by phagocytes and opsonins

In Hours

Question 19

Explain how fungal pathogens are recognised by the innate immune system

Answer 19

Involvement of distinct pattern-recognition receptors (PRRs) which recognise PAMPs and DAMPs (pathogen/damage-associated molecular patterns)

TLRs (toll-like receptors – a type
of pattern receptor) plays a key role in activation

These mechanisms are followed hours later by an inflammatory response. These early phases help to keep infection under control.

Question 20

What is the fungal cell wall composed of

Answer 20

predominantly of glucans and chitin (offering physical protection) as well as PAMPs

composition is in permanent flux according to the environment and morphotype of the organism

Question 21

What occurs if the infectious fungal pathogen breaches the early lines of defence

Answer 21

Adaptive immune response
Generation of antigen specific Th, Treg and B cells that target the pathogen and induce memory cells to prevent subsequent infection

Question 22

Both the host and the pathogen are responsible for damage sustained during infection. Describe how damage can be mediated by the host response

Answer 22

Pathogens that cause damage in hosts with extremely weak immune responses will often cause invasive disease

Pathogens that cause damage in hosts where an overly strong immune response takes place may result in allergy, and the damage sustained during infection is also due to the host, eg Aspergillus fumigatus

Question 23

Give examples of major anti fungal effector cells

Answer 23

Neutrophil
Macrophage
Dendritic cells

Question 24

What is the role of dendritic cells in fungal infection

Answer 24

Dendritic cells sample fungi at the site of colonisation, transport antigens to the draining lymph nodes and activate disparate Th and Treg cells in a morphotype- and tissue-dependent manner

Question 25

What does the word ‘dichotomous’ describe

Answer 25

each cell has a direct role in killing fungi, as well as a facilitative role in production of cytokines + antigen presentation

Innate immune recognition/surveillance of fungi is dichotomous

Question 26

Give examples of antifungals

Answer 26

Tacrolimus
Mycophenolate mofetil
Interferon-γ

Question 27

How does tacrolimus assist in fungal clearance

Answer 27

has antifungal properties and also inhibits calcineurin and thus IL-2 secretion by T cells. Streptomyces tsukubaensis produces it.

Question 28

How does Mycophenolate mofetil assist in fungal clearance

Answer 28

antifungal which inhibits lymphocyte proliferation. It’s also a mycotoxin, as it’s produced by a fungus: Penicillium brevicompactum.

Question 29

How does Interferon-γ assist in fungal clearance

Answer 29

enhances clearance of fungal infections by suppressing IL-10, allowing more inflammation.