Immunity to fungal infections

Question 1

How often does fungi cause human infection?

Answer 1

Only a small percentage of thousands of fungal species are known to cause human infecton

Question 2

What important fungi are there in terms of causing human infection?

Answer 2

Candida, aspergillus and cryptococcus species

Question 3

What type of pathogens are most fungal pathogens?

Answer 3

Opportunistic- only causing infections and disease when host defences are breached

Question 4

Why are patients with cancer at particular risk of fungal infection?

Answer 4

They are often immunocompromised either because of their underlying malignancy and/or treatment

Question 5

What other patients apart from cancer are at risk of fungal infection?

Answer 5

Aids patients and transplant recipients

Question 6

What fungal infection is linked with aids?

Answer 6

Pneumocystis pneumonia caused by pneumonia jirovecii

Question 7

Which patients are at incredibly high risk of fungal infection?

Answer 7

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)

Question 8

What affects the immune response to fungi?

Answer 8

Species encountered, anatomical site of infection and fungal morphotype

Question 9

How is the fungal morphotype an important determinant of the host response?

Answer 9

Yeasts and spores are often effectively phagocytosed, the larger size of hyphae precludes effective ingestion

Question 10

What are the fundamentally important antifungal effector cells?

Answer 10

Neutrophils, macrophages and monocytes

Question 11

What are the critical first line of defence against fungal infection?

Answer 11

Phagocytes

Question 12

How are fungal cell walls targeted by immune system?

Answer 12

They are fundamentally different in structure from human plasma membranes and are sensed by pattern recognition receptors of innate immunity

Question 13

What other receptors are involved in sensing other fungal components?

Answer 13

Toll-like receptors

Question 14

Describe a classic response to fungal infection?

Answer 14

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

Question 15

What effect do fungi have on complement system?

Answer 15

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

Question 16

What does normal human serum contain in terms of fungi?

Answer 16

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).

Question 17

When does activation of lectin pathway occur?

Answer 17

When recognition of exposed mannans by mannose-binding lectin (MBL) triggers MBL-associated serine proteases.

Question 18

What effect does complement deficiency have in mice’s response to fungal infection?

Answer 18

It makes them more susceptible to experimental mycoses

Question 19

What do patients with rare genetic condition chronic granulomatous disease (CGD) have?

Answer 19

They have defects in the enzyme NADPH oxidase and their neutrophils are unable to kill ingested pathogens

Question 20

What are chronic granulomatous disease patients susceptible to?

Answer 20

Invasive fungal infections, particularly with Aspergillus species, confirming the crucial role of neutrophils in defence against fungal infections

Question 21

What do dendritic cells have a fundamental role in?

Answer 21

Linking innate and adaptive responses to a range of pathogenic fungi including aspergillus fumigatus, cryptococcus neoformans and candia albicans

Question 22

What activates dendritic cell signalling?

Answer 22

Exposure to fungi

Question 23

What do signals transmitted by dendritic cells vary depending on?

Answer 23

Encountered fungus and its morphotype, helping to shape the appropriate adaptive immune response

Question 24

What type of responses predominate in protective responses to various fungal infections?

Answer 24

Th1 type CD4+ T cell responses- interferon gamma is known to be a particularly important cytokine in this type of response