1: Fungal Infections Flashcards
What are the different types of fungi that can casue disease?
- Chytridiomycota
- Zygomycota
- Basidiomycota
- Ascomycota
What type of Fungi is Aspergillus?
It is a type of ascomycota
- spore forming
What type of fungi it Cryptococcus neoformans?
It is a yeast
- pathogen in immunocompormised
- might lead to yeast growth in the brain (cryptococcomas)
Describe the immune response to a fungal infection
Varies depending on species and site of infection
Innate immune response:
- Fungus gets to circulation
- Gets opsonised (have very different surface –> activation of complement system! C3 actication, but no complement mediated lysis )
- and Phagocytosed (by Magrophages and neurtrophils)
- NK cells produce IF-gamma
Adaptive Immune response:
- Dendritic cells present antigen and influence T-cell differentiation
- Th1 and Th17 play a role
Explain how Candida Albicans can cause disease
Candidal dimorphism (yeast/hyphal forms) allows tissue invasion
Explain how Crytpococcus can cause disease
Crytpococcus forms a capsule to evade phagocytosis
Explain how an infection with Aspergillus can cause disease
Aspergillus species inhaled as conidia, invade tissues as hyphae
What is the TOLL receptor?
It is a receptor involved in pattern recognition receptor for fungal immunity
Explain the relationship between Human Dectin 1 Deficiency and Mucocutaneous Fungal Infections
Human 1 Dectin= is a receptor involved in pattern recognition of fungal infections
- if it is deficient: increased rate of fungal infections
Explain the relationship between Human CARD9 Deficiency and Chronic Mucocutaneous Candidiasis
Human CARD9 is needed for TNF-alpha production and T-cell differentiation (Th17)
- if not there
- increased rate and risk of fungal infections
Explain the role of Toll-like receptors and fungal infections
Toll-Like receptors are polymorphic (e.g. TLR4+9)
- in some variants (or in loss of function) : riks of asperfillos infection is increased
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Name some defects that can cause defects host immunity and make you more suspectible to fungal infections
- Human Dectin 1 Deficiency
- Human CARD9 Deficiency
- TLR4
- TLR9
- Plaminogen alleles influence suspectibility to aspergillus in mice (and stem cell transplantation)
What is the role of macrophages and neutrophils in the control of fungal infections?
- Both Macrophages and neutrophils play a role but NEUTOPHILS are more important! (Expecially in Aspergillus fumigatus infectio)
- Involved in phagocytosis but more important:
- Neutophils form DNA networks that trap fungal spores
Explain the role of T-cells in immunity to fungal infections
- Th1= involved in spore cells and single cell depletion
- Th2= involved in defence against multicellular fungi
Explain the role of Interferon Gamma in fungal infections
Important –> causes Down-regulation of IL-10 and a Burst of Inflammatory Cytokine Expression
Explain the The damage response framework of microbial pathogenesis
The right level of immune response must be met to
- Fight the infection (not too low)
- But also not to develop allergy/ too strong host response
Explain the relationship between fungi and allergy
- 16% of all allergens are fungi
- Fungi are inhaled daily and spored can get deep in lung
- Aspergillus is primary driver
- Allergic responses include
- Type I and IV hypersensitivity driven
- often dentritic cells are abnromal cause T cell activation and B-cell class switching –> IgE production
What is allergic bronchopulmonary aspergillosis?
Allergic response to apergillus
- common in astmah/CF patients
- causes inflammation leading to
- bronchiectasis –> abnromal dilation of airways
- mucus plug in airways
- damage lung tissue and lead to scaring
What kind of pathogens are most fungi?
Most fungi pathogens: opportunistic
–> need immunocompromisation before it can develop disease
Explain the relationship between chronic granulomatous disease (CGD) and fungal infections
CGD= defects in NADPH oxidase –> neutrophils can’t kill digested pathogens –> suspectible to fungal (expecially Aspergillus) infections
Explain the role of dendritic cells in immune response against fungi
Important in linking innate and adaptive immune response
–> Activate depending on type of fungal infection
- Th1 (CD4+) and interferon gamma —> important in defence against infections
What are the most important fungal species tha might cause pathology?
Candida, Aspergillus and Cryptococcus species.
What is a fungal morphotype?
They are distinct growth forms of a fungus
