Immunity to fungal infections Flashcards
How often does fungi cause human infection?
Only a small percentage of thousands of fungal species are known to cause human infecton
What important fungi are there in terms of causing human infection?
Candida, aspergillus and cryptococcus species
What type of pathogens are most fungal pathogens?
Opportunistic- only causing infections and disease when host defences are breached
Why are patients with cancer at particular risk of fungal infection?
They are often immunocompromised either because of their underlying malignancy and/or treatment
What other patients apart from cancer are at risk of fungal infection?
Aids patients and transplant recipients
What fungal infection is linked with aids?
Pneumocystis pneumonia caused by pneumonia jirovecii
Which patients are at incredibly high risk of fungal infection?
Patients with prolonged and profound neutropenia (low neutrophil count) after treatment with highly cytotoxic chemotherapy for haematological malignancies and recipients of haematopoietic stem cell transplantation (HSCT)
What affects the immune response to fungi?
Species encountered, anatomical site of infection and fungal morphotype
How is the fungal morphotype an important determinant of the host response?
Yeasts and spores are often effectively phagocytosed, the larger size of hyphae precludes effective ingestion
What are the fundamentally important antifungal effector cells?
Neutrophils, macrophages and monocytes
What are the critical first line of defence against fungal infection?
Phagocytes
How are fungal cell walls targeted by immune system?
They are fundamentally different in structure from human plasma membranes and are sensed by pattern recognition receptors of innate immunity
What other receptors are involved in sensing other fungal components?
Toll-like receptors
Describe a classic response to fungal infection?
Phagocytes residing in target organs attempt to kill fungi. Additional effector cells including neutrophils and monocytes are recruited to sites of infection by action of inflammatory signals such as cytokines, chemokines and complement components
What effect do fungi have on complement system?
They are potent activators of complement system resulting in opsonisation due to deposition of C3b on fungal surface and recruitment of inflammatory cells as a result of C3a and C5a generation.
However fungi are resistant to complement-mediated lysis, presumably due to thick cell wall. They can activate classical, alternative and lectin complement pathways
What does normal human serum contain in terms of fungi?
It contains antibodies to fungal cell wall components, particularly mannans, that can initiate classical pathway activation upon binding. Such antibodies may also directly opsonise fungi for recognition by phagocytic Fc receptors (FcRs).
When does activation of lectin pathway occur?
When recognition of exposed mannans by mannose-binding lectin (MBL) triggers MBL-associated serine proteases.
What effect does complement deficiency have in mice’s response to fungal infection?
It makes them more susceptible to experimental mycoses
What do patients with rare genetic condition chronic granulomatous disease (CGD) have?
They have defects in the enzyme NADPH oxidase and their neutrophils are unable to kill ingested pathogens
What are chronic granulomatous disease patients susceptible to?
Invasive fungal infections, particularly with Aspergillus species, confirming the crucial role of neutrophils in defence against fungal infections
What do dendritic cells have a fundamental role in?
Linking innate and adaptive responses to a range of pathogenic fungi including aspergillus fumigatus, cryptococcus neoformans and candia albicans
What activates dendritic cell signalling?
Exposure to fungi
What do signals transmitted by dendritic cells vary depending on?
Encountered fungus and its morphotype, helping to shape the appropriate adaptive immune response
What type of responses predominate in protective responses to various fungal infections?
Th1 type CD4+ T cell responses- interferon gamma is known to be a particularly important cytokine in this type of response
