1. Immunity to fungal infections Flashcards
What causes pneumocystis pneumonia (PCP) and what is it associated with?
- Pneumocystis jirovecii
* Associated with AIDS
What patients are at particular high risk of fungal infections?
- Patients with prolonged and profound neutropenia after treatment with highly cytotoxic chemotherapy for haematological malignancies
- Recipients of haematopoietic stem cell transplantation
How can fungal morphology affect the host response?
Larger sized (e.g. hyphae) preclude effective ingestion compared to yeasts and spores
Which cells have a role in linking innate and adaptive response to a range of pathogenic fungi?
Dendritic cells
Which cell type predominates in protective responses to various fungal infections, and which cytokine is important in this response?
- Th1 type CD4+ T cell
* interferon-γ
Is innate or adaptive immunity more important in fungal infection?
Innate
Outline the cellular immune response to fungal infection
- Opsonisation by pentraxin 3 and mannose-binding lectin
- Phagocytes - first line of defence
- NK cells - provide interferon-γ
• Failure of innate immunity leads to adaptive responses:
- dendritic cells influence T cell differentiation
- Th1 and Th17 play a role
What is Candidal dimorphism?
Grows in yeast and hyphal forms - allows tissue invasion
In what form does Aspergillus invade tissues?
Hyphae
How are fungal cells detected?
- Cell walls sensed by pattern recognition receptors
* Toll like receptors
How are Toll like receptors (TLR) important in fungal immunity and complement?
- Sense fungal components
- Expressed on sentinel cells (macrophages and dendritic cells)
- Activate immune cell responses - recruiting neutrophils and monocytes using cytokines, chemokines etc.
- Complement activated - opsonisation due to deposition of C3b on fungal surface
- Recruitment of inflammatory cells due to C3a and C5a generation
Which complement pathways can fungi activate?
Classical, alternative and lectin
What complement activity are fungi resistant to?
Complement-mediated lysis (due to thick cell wall)
Which antibodies in normal human serum are involved in a fungal cell response and how?
- Antibodies to fungal cell wall components
- Particularly mannans - can initiate classical pathway activation upon binding
- May directly opsonise fungi for recognition by phagocytic Fc receptors (FcRs)
When does activation of the lectin pathway occur (with reference to mannans)?
When recognition of exposed mannans by mannose-binding lectin (MBL) triggers MBL-associated serine proteases
Summarise Human Dectin 1 Deficiency
- HD1 is normally important in the phagocytosis of Candida and the immunity to chronic mucocutaneous candidiasis
- Loss of function mutation - mendelian susceptibility to chronic mucocutaneous cadidiasis
- Homozygous mutation - reduced inflammatory response via IL-6