L6 - Extracellular pathogens II Flashcards
What are innate host defences of the skin/mucosal surfaces?
resistant to infection unless broken
mucociliary escalator
urinary tratcs
What are innate host defences of pH?
hostile for fungal growth
What are innate host defences of the antimicrobial secretions
active against some fungi
antimicrobial peptides in skin
B-defensins in gut
a-defensins in neutrophils
What are the innate host defences of the complement cascade
classical pathway (immune complexes)
lectin pathway (terminal mannose residues)
alternative pathway (LPS, yeast cell wall)
What are the innate host defences of phagocytes?
neutrophils
monocytes
macrophages
dendritic cells
What is mucositis?
sore inflamattion
occurs are irradiation of cytotoxic drugs when prepare for bone marrow transplant
Can the membrane attack complex cause lysis of fungi?
NO - can act as opsonins but does NOT LYSE LIKE IT WOULD BACTERIA
complement binds to outer part of fungi - cause inflammation & phagocytic attack
How does candida interact with the complement cascade?
activates all 3 pathways
promotes phagocytosis by macrophages & neutrophils
How does aspergillus interact with the complement cascade?
complement deficiency = ^ susceptibility to invasive disease
less C’ deposition on pathogenic species
What is neutropenia?
reduce No. of neutrophils
What are predisposing factors for invasive fungal disease?
neutropenia
functional problems with neutrophils
What are common fungal PAMPs?
chitin
glucans
mannosylated proteins
how many PRRs do PAMPs interact with?
sometimes 1
sometimes multiples
How are fungi internalised in phagocytosis?
actin dependent process
form phagosome
How does the phagosome mature?
fusion with vesicles = phagolysosome
acidification
digest fungi into individual antigens
How does phagocytic killing of fungi by OXIDATIVE mechanisms occur?
“respiratory burst”
ROS (candida, aspergillus)
RNI (cryptococcus)
How does phagocytic killing of fungi by NON-OXIDATIVE mechanisms occur?
Anti-microbial peptides
hydrolases
limitation of nutrients (zinc sequestration)
What is the role of Th1 in fungal immunity?
protective response
activate phagocytic cells by TNF, IL-12 and IFNy
What is the role of Th2 in fungal immunity?
harmful in response fungal infection
unfavourable for aspergillus and candida
allergic responses, disease relapse
IL-4, IL-66, IL-13
What is the role of Th17 in fungal immunity?
induces release of AMPs
favourable with mucocutaneous cadidosis
epithelial expression of chemotactic factors
IL-17, IL-22, IL-23
What are immune responses in normal individuals?
macrophages/neutrophils recruited
migrate to draining lymph node
APC
Th1 = pro-inflammatory, enhance clearance
Th2 = dampen immune response
What are immune defects due to haematological malignancy?
decreased No. neutrophils
decreased No. of dendritic cells in ALL
defects in neutrophils in CLL
^ Treg cells in CLL = suppressed function
What are immune defects to chemotherapy and HSCT?
decreased No. neutrophils
steroids suppress further
chemotherapy impairs dendritic cell function
radiotherapy - lymphopenia
chemotherapy reduces No. B cells & disrupts cytokine networks
What are immune defects in HIV/AIDS?
abnormal phagocytosis
impaired maturation - bad APCs
T-cells destroyed
deranged cytokine networks
impaired antibody responses
Immune defects after solid organ transplantation?
doesn’t affect neutrophils
Cyclosporine inhibit activation of CD4 cells and many ILs
Moabs = T-cell depletion
B-cells inhibited by Sirolimus
