Dear Immune Team
Listening to BBC Radio Five last week I heard mention of a rare immune system reaction that I was previously unaware of – the abscopal effect. This is a reaction when localised high dose radiotherapy is given to a cancer patient and results not only in remission at the radiotherapy site but also at metastatic sites throughout the body, sometimes resulting in complete remission.
This has been known about since the 1950s but only recently has much progress been made in understanding the effect. The abscopal effect has been more frequently observed since the introduction of the immune checkpoint blocking antibodies Ipilimumab and pembrolizumab.
I think the abscopal effect would be an interesting topic for discussion on Immune.
I include links to some recent literature:
Dear Immune Hosts,
I hope this finds you well and that you are all enjoying the transition to spring.
With the advent of smartphones I discovered the availability of podcasts and quickly stumbled across the offerings of Microbe TV, all of which I enjoy and have taken up the daunting challenge of delving through your years of archival material.
Up until mid-January of this year, my interest in catching up on some of the latest advances in microbiology was based on curiosity and interest I have always maintained for the subject (I studied and worked as a Microbiologist in the 80s & 90s, but left that aspect of my career in 2000). However, now it has become a personal priority to re-educate myself, especially with respect to the immune system because out of the blue, with no prior issues or family history, and being healthy and physically active, I was suddenly hit with a bout of severe ulcerative pancolitis. I lost 30 lbs. (about 20% of my body weight) and had my life turned upside down. 7+ weeks of bloody diarrhea 24/7 has pretty much rendered me housebound.
Anyway, with the advent of Immune, especially 3, 4 & 5, I feel like I hit a jackpot of clearly presented and thoughtful discussion on topics that now have relevance to my personal situation.
As I understand it the cause of colitis is not known, It does not seem to be diet-related, but may be triggered by an infection or a parasite, or it may involve an inappropriate inflammation response to constituents of the normal microbiome. At the time my testing was done, all results for possible causes were negative.
In order to try to suppress the inflammatory response in the colon and hopefully achieve remission, I have begun infusions of infliximab (Remicade) a TNF alpha inhibitor which is a chimeric human/murine IgG, the binding epitope for TNF alpha being of murine origin. Three weeks into therapy I believe I’m beginning to see some improvement, fingers crossed. It is humbling to be in a position to benefit from all of the research and development that has come together so far to help provide viable treatments for this condition.
Regarding costs of this treatment, although I have not seen actual numbers, I have read each infusion costs upwards of $4000 CD. The dosing involves an infusion of Remicade at 0, 2 & 6 weeks, then every 8 weeks thereafter. Apparently there are biosimilar or “subsequent entry biologics” such as Inflectra that are available at reduced costs. (A discussion on overall costs and options for these therapies at the State/Federal level and in different countries might be interesting.) In any event, here, patients prescribed Remicade are registered into a Patient Support program. In my case, coverage is first from my work benefits (which happens to cover 80%) then the balance is covered through the health care system and the Patient Support program. We are assigned a coordinator who takes care of all of the insurance and cost aspects of the treatment and, even if I were to lose my coverage from work, they would be able to provide any additional coverage required so that, in the end, there is no direct cost to the patient. Needless to say I have no plans to ever leave the boundaries of this health care system.
Any coverage of the normal intestine vs. Crohn’s/colitis/IBS or similar autoimmune diseases, TNF inhibitors &/or alternative therapies, and the underlying immune response would be most welcome.
Thank you for taking the time and effort to bring this production to fruition.
There was a slightly unclear explanation in the intro. [ep. 5]
pIgR transports dimeric IgA, not monomeric IgA. The pIgR gets cleaved and remains as the secretory component on secretory (dimeric) IgA. The J-chain, that conveys dimer formation of IgA is already synthesized in the IgA secreting plasma cell.
Dear Immune team,
I am a listener of your podcasts (TWIM and Immune).
Following your podcast number 7 from the 18th of April; please find hereunder a brief description of a neuroBorreliosis inducing Alzheimer idea/model:
Idea/Model to consider:
1/ NeuroBorreliosis activates the Amyloid Precursor Protein (APP) and the Toll Like Receptor 2 (TLR2)
2/ APP activation increases C1q from the complement system
3/ C1q activates Microglia
4/ TLR2 activates Microglia
5/ Borrelia deactivates the C3b pathway via factor H protein, then stop the MAC system (=> very interesting article with very good diagrams)
NeuroBorreliosis triggers activation of the early complement pathway and microglia, BUT borrelia blocks the second part of the complement systems via deactivating the C3b (so no C4-> C5 .. -C8-> C9 => no more MAC ‘attack’ system)
Borrelia triggers an innate immune over-reaction (C1q to C3b and microglia) but blocks the end of the Complement pathway for its own survival.
Articles to support the model
1/ How borrelia activates the APP (Amyloid Precursor Protein), and TLR2
2/ How increasing production of APP triggers an increase of the C1q from the Complement pathway.
3/ How C1q activates Microglia
4/ How TLR2 activates Microglia
5/ How borrelia deactivate the C3b of the complement system via Factor H family protein
I stay at your disposal
Phelix – London, Leicester & Paris