Immunity to fungal infections Flashcards
Describe the morphogenesis of candida
Candida show dimorphism (two forms, yeast buds or hyphae) which allows for invasion
Describe the morphogenesis of Crytpococcus
Forms a capsule to evade phagocytosis
Describe the morphogenesis of Aspergillus
invades tissues as hyphae
How do aspergillius species infiltrate the body
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
How are mycoses classified by level of tissue affected
Superficial. Cutaneous and subcutaneous (affect primarily the skin and subcutaneous tissues)
Systemic (deep infection which spreads around the body)
Compare primary/true pathogens to opportunistic pathogens
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
What does yeast mean
describes single-celled fungal morphotypes such as those exhibited by C. albicans and C. neoformans
What is the difference between C. neoformans and candida albicans
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
Describe pseudohyphal cells
lack the dividing partitions known as septa found in true hyphae
What is a mycelium
A fungal colony composed of multiple branches hyphae
Give examples of how fungi infects humans
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
What are the risk factors for deep infection
Chemotherapy
Surgery
Catheterisation
AIDS
Explain how candida species are able to infiltrate into the body
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.
Which immune defence mechanism in its absence allows aspergillum species to infect
Normally, ciliary clearance and pulmonary polymorphonuclear leukocytes protect effectively against infection
Absence - germinate and go on to produce a lesion in the lung
Why is it difficult to develop vaccines against fungal infections
immune response varies according to site of infection, species and morphotype
What is the first line of defence against fungal pathogens
physical
On the skin, or oral/pulmonary/gastrointestinal mucosa
What is the role of pathogens in defence against fungal pathogens
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.
Which cells are involved the destruction of fungi (normal) by innate defence mechanisms and how long does it take
Mediated by phagocytes and opsonins
In Hours
Explain how fungal pathogens are recognised by the innate immune system
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.
What is the fungal cell wall composed of
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
What occurs if the infectious fungal pathogen breaches the early lines of defence
Adaptive immune response
Generation of antigen specific Th, Treg and B cells that target the pathogen and induce memory cells to prevent subsequent infection
Both the host and the pathogen are responsible for damage sustained during infection. Describe how damage can be mediated by the host response
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
Give examples of major anti fungal effector cells
Neutrophil
Macrophage
Dendritic cells
What is the role of dendritic cells in fungal infection
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
What does the word ‘dichotomous’ describe
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
Give examples of antifungals
Tacrolimus
Mycophenolate mofetil
Interferon-γ
How does tacrolimus assist in fungal clearance
has antifungal properties and also inhibits calcineurin and thus IL-2 secretion by T cells. Streptomyces tsukubaensis produces it.
How does Mycophenolate mofetil assist in fungal clearance
antifungal which inhibits lymphocyte proliferation. It’s also a mycotoxin, as it’s produced by a fungus: Penicillium brevicompactum.
How does Interferon-γ assist in fungal clearance
enhances clearance of fungal infections by suppressing IL-10, allowing more inflammation.
