Today in class we began a discussion about what would happen to the central nervous system if the blood brain barrier was penetrated, i.e., would the immune system attack the central nervous system? Multiple sclerosis, a disease often described as an autoimmune disease, speaks to this discussion. It affects 250-350,000 people in the U.S., ages 15-60. It is twice as common in women and whites. Many scientists believe it is an autoimmune disease, in which the blood brain barrier is broken down, allowing for the immune system to attack myelin, or more specifically myelin basic protein. As such, a variety of immunosuppressants have been trialed as potential treatments, including Cytoxan, Imuran and mitoxantrone, along with plasmapheresis and bone marrow transplant. The NIH has a great website that provides an overview of this disease ( http://www.ninds.nih.gov/disorders/multiple_sclerosis/detail_multiple_sclerosis.htm) if you aren't particulalrly familiar with it.
These 2 review papers delves into these areas more deeply, discussing specific chemokines and also the potential role of T regs:
Biochim Biophys Acta. 2011 Feb;1812(2):220-30. Epub 2010 Aug 6.
The blood-brain barrier, chemokines and multiple sclerosis.
Holman DW, Klein RS, Ransohoff RM.
J Clin Immunol. 2008 Nov;28(6):697-706. Epub 2008 Sep 2.
Multiple sclerosis and regulatory T cells.
Costantino CM, Baecher-Allan C, Hafler DA.
Enjoy.
This doesn't have anything to do with multiple sclerosis, but you might find it interesting if you're looking and talking about immune privileged sites. It's a really new paper that was just published in Nature but has already made huge headway in the immunology community, being commented on in the New England Journal of Medicine. It talks about how Treg are responsible for stem cell regulation and survival after bone marrow transplant. Both the original Nature article and the NEJM comment are below, if you want to take a look.
ReplyDeleteNature. 2011 Jun 8;474(7350):216-9. doi: 10.1038/nature10160.
In vivo imaging of Treg cells providing immune privilege to the haematopoietic stem-cell niche.
N Engl J Med. 2011 Sep 8;365(10):956-7.
Illuminating immune privilege--a role for regulatory T cells in preventing rejection.
The blog mentions that MS is twice as common in women and whites. I did some searching and found an article in the Multiple Sclerosis Journal that talks about how the difference HLA-DR allele polymorphism is associated with greater risk or resistance in certain groups of people. Honestly, it made me more confused on what other factors may contribute to the differences.
ReplyDeleteHLA-DR allele polymorphism and multiple sclerosis in Chinese populations: a meta-analysis.
Qiu W, James I, Carroll WM, Mastaglia FL, Kermode AG.
Mult Scler. 2011 Apr;17(4):382-8. Epub 2010 Dec 21.
PMID:
21177322
[PubMed - indexed for MEDLINE]
I imagine blood brain barrier is essential for the survival of the organism. In absence of BBB immune system would make antibodies to a whole new range of antigens that APCs have never seen before. Although most of the antigens probably will not be immunogenic. I think, a more serious problem would be the infection of immunoprivileged sites with common agents. For example Herpes Simplex Virus-1 is dormid in most of the population and an otherwise innocent cold sore would cause HSV-1 encephalitis in absence of BBB.
ReplyDelete