Iron & Immune System Flashcards
What is lipocalin 2?
A small protein expressed by neutrophils and macrophages.
Binds bacterial siderophore enterobactin (produced by gram -ve bacteria to scavenge iron)
Also may bind mammalian siderophore –> affects host iron homeostasis.
What concentrations of iron are needed by most bacteria?
Give an example of a bacterium which has circumvented iron requirements.
10-6 to 10-7 M Borrelia spp (lyme disease) - lost all of iron regulated proteins and genes.
What is significant concerning the Hmu system?
Non-essential to cause infection if subcutaneously injected into mice. Required for IV administration - is there another iron acquisition system?
What evidence has been used to demonstrate the importance of host - pathogen iron balance?
1991 - used different types of macrophages to see which could kill Listeria monocytogenes.
- High TfR and low TfR couldn’t - intermediate TfR could
Epidemiological - haemochromatosis patients have enhanced incidence of Salmonella and Yersinia infections.
Why is Lactoferrin not good at overloading iron in mice?
They excrete it!!
How does the immune system modulate hepcidin?
IL-1 and IL-6 stimulate its production (anti-inflammatory)
TNF-a blocks hepcidin expression in hepatocytes (PROINFLAMMATORY)
How does iron affect the innate immune system?
Killing of Salmonella inside mphages - either production of O or N free radicals.
Measure H2O2 after activation (OD)
DEF (chelated) group show lower H2O2 and therefore can’t effectively mount an immune response
What happens to EPO during anaemia of chronic disease?
Blunted formation and activity.
Impaired proliferation of erythroid progenitor cells
EPO via distinct receptors… inhibits NF-kB. As NF-kB induces iNOS, TNF-a, IL-6 and IL-12, inhibition –> impaired immune control.
Reduction in Epo in ACD sustains pro-inflammatory response and improves control of S. Typhimurium
What are the effects of NO on the immune system?
Regulates binding affinity of IRPs to IREs.
Cell iron content regulates iNOS transcription.
NO activates Nrf2 binding to ferroportin promoter –> increased FpN expression.
