Fungal Immunity - 03.03.2020 Flashcards
What are some common fungal pathogens in humans
- aspergillus (-> aspergilloma)
- cryptococcus neoformans
- Candida albicans
Overview of cellular immunity to fungal infections
- Opsonization by pentraxin 3 and mannose-binding lectin
- Phagocytes are a critical first line of defense NK cells provide early interferon-gamma
- A failure of innate immunity leads to adaptive responses
- Dendritic cells influence T cell differentiation
- Th1 and Th17 play a role
Which mutations give increased susceptibility to fungal disease?
Dectin-1
TLR4
plasminogen
Which mutations give increased susceptibility to fungal disease?
Dectin-1
TLR4
plasminogen
Which fungus is penicillin similar to?
Aspergillus
Pathophysiology of allergic bronchopulmonary aspergillosis
- abnormalities in dendritic cell responses
- priming of B cell class switch to IgE ressponse
- this causes mast cell granulation
Criteria for allergic bronchopulmonary aspergillosis
Predisposing conditions
- Asthma or cystic fibrosis
Obligatory criteria
- Total baseline serum IgE >1000 IU/ml
- Positive immediate hypersensitivity skin test or Aspergillus-specific IgE
Supportive criteria (more than 2 present)
- Eosinophilia >500cells/ul
- Serum precipitating or IgG antibodies to Aspergillus fumigatus
- Consistent radiographic abnormalities
Criteria for allergic bronchopulmonary aspergillosis
Predisposing conditions
- Asthma or cystic fibrosis
Obligatory criteria
- Total baseline serum IgE >1000 IU/ml
- Positive immediate hypersensitivity skin test or Aspergillus-specific IgE
Supportive criteria (more than 2 present)
- Eosinophilia >500cells/ul
- Serum precipitating or IgG antibodies to Aspergillus fumigatus
- Consistent radiographic abnormalities
Radiological features of ABPA
Dilated bronchi with thick walls Ring or linear opacities
Upper or central region predeliction Proximal bronchiectasis
Lobar collapse due to mucous impaction Fibrotic scarring
Management of ABPA
- Corticosteroids
- Itraconazole for steroid sparing effect
- Benefit of itraconazole past 16 weeks unclear
- Reduction in circulating IgE, steroid dependency and improved PFT
- Itraconazole indicated if not responding to steroids or steroid- dependent
- Role of inhaled steroids and other antifungals less clear
- Recombinant IgE monoclonal antibodies (omalizumab) may be useful
Aspergillus rhinosinusitis
- May be allergic or invasive
- Increasingly common
- Association with atopy and nasal polyposis
- Raised total IgE, skin test and Aspergillus-specific RAST IgE (or sometimes IgG)
- May also be caused by Bipolaris or Curvularia
- Obliterated sinuses with hypo attenuated mucosa and enhancing material on imaging
Treatment of fungal sinusitis
- Oral corticosteroids
- Surgical removal of obstructing nasal tissue
- Systemic anti-fungal treatment has not been shown to be effective
- Topical therapies being investigated
