Re: [DIYbio] Re: Genetic engineering at home

• New T-cells (and B-cells) with randomly generated receptors are produced throughout life, although it does slow down as you get older.
  
• T-cells mature in the thymus and auto-reactive cells are eliminated there...not the spleen :)   ...B-cells mature in the bone marrow, and auto-reactive B-cell also get eliminated.  This is called Central Tolerance.  This is why if you were born with GFP, you would probably not develop an immune reaction to it.  However T-cells are long-lived so if you introduce it later, it's too late for central tolerance.
  
• Central tolerance is not 100% effective...some self-reactive cells get through, especially cells that react to proteins not normally found in the thymus/bone marrow.  This is why we also have "peripheral tolerance".  If the immune system finds an unknown protein, it is actually fairly likely to produce a T-regulatory response that suppresses reactive cells.   However, if there is inflammation going on (as in infection) or it's large dose or especially immunologic protein, T-effector responses will dominate.  The cell interactions that produce either peripheral tolerance or activation happen mostly in the 2ndry lymphoid organs, such as spleen and lymph nodes.
• Peripheral tolerance breaking down is an important part of autoimmune disease.
  
• Immunology sometimes feels more like sociology than biology--lots of cells making chemical "arguments" back and forth, and it can be hard to predict with ones will win and give you tolerance or rejection!
• Cathal mentioned activating T-cells to fight cancer.  This is a great topic and makes me geek out a bit :)  There has been slow progress over the last decade, with some promising clinical trials.  It's a great poster-child for gene therapy.
• Some links...
• Central tolerance:  http://en.wikipedia.org/wiki/Central_tolerance
  
• Peripheral tolerance:  http://en.wikipedia.org/wiki/Peripheral_tolerance
• Example of T-cell therapy for lymphoma: http://www.chop.edu/service/oncology/pediatric-cancer-research/t-cell-therapy.html
• Obligatory XKCD: http://www.xkcd.com/938/
  

Mike

basically the immune system undergoes a sort-of imprinting/learning,
where any immune cells that react with cell-presented proteins are
killed. I'm not sure if this happens more during embryo development,
or is constant throughout life, or if it tapers off.

Since the immune system adapts by VDJ recombination (gene
jumping/randomization), killing off reactionary cells during a safe
time (or in a safe place) makes the odds of the immune system
attacking itself very low.

Eventually I guess VDJ recombination could come up with a new matching
motif/sequence, which could be how these autoimmune things happen late
in life.

http://en.wikipedia.org/wiki/V(D)J_recombination
(http://de.wikipedia.org/wiki/V(D)J-Rekombination)

http://en.wikipedia.org/wiki/Negative_selection_(immunology)

Also:
http://en.wikipedia.org/wiki/T_cell#Negative_selection

On Fri, Jan 3, 2014 at 10:23 AM, Andreas Stuermer
<masters...@gmail.com> wrote:
> I mean the immune system of the resulting baby, of course.
>
>
> On Fri, Jan 3, 2014 at 7:22 PM, Andreas Stuermer <masters...@gmail.com>
> wrote:
>>
>> I guess I gotta dig into immunology! Especially now that the
>> immunology-lecture at my university has been cancelled for financial
>> reasons.
>>
>> How can the immune sytem know GFP is new?
>>
>> What if two humans interbreed and one has a mutant protein? Why doesn't
>> the immune system attack that protein, and does attack GFP??
>>
>>
>>
>>
>> On Fri, Jan 3, 2014 at 6:03 PM, Mike Horwath <mike...@gmail.com> wrote:
>>>
>>> Cathal you really summed up these issues nicely!  I few more points for
>>> people interested in this stuff:
>>>
>>> Some proteins are inherently more immunogenic than others.  Sometimes,
>>> they just don't have good epitopes for antibodies to target, and/or
>>> fragments from them don't fit well into MCHII molecules for presentation to
>>> T cells.  GFP however seems to be pretty immunogenic:
>>> http://www.ncbi.nlm.nih.gov/pubmed/10455440
>>> "Immune Privilege" for the brain and eye is the result of active immune
>>> suppression plus physical barriers to immune cell entry (lack of lymphatics,
>>> blood-brain barrier).  However, this privilege can and does fail...see
>>> multiple sclerosis and symphathetic opthalmia, for example.
>>> I agree that engineering infrared vision is way beyond current
>>> capabilities :)
>>>
>>> Mike (immunology grad student)
>>>
>>>
>>>
>>> On Thursday, January 2, 2014 11:32:46 AM UTC-5, Cathal Garvey wrote:
>>>>
>>>> Allergy wouldn't be the same reaction.
>>>>
>>>> With GFP exposure outside cells, you'd expect no reaction at first, and
>>>> if an allergy results, then on later exposure you'd get swelling,
>>>> etcetera.
>>>>
>>>> With GFP *inside cells*, you'd expect immune to seek out any cell
>>>> bearing the GFP antigen, and trigger apotosis in those cells or
>>>> *degranulate on their asses*.
>>>>
>>>> So, not just inflammation, but destruction of cells in the area by the
>>>> immune system. If enough cells are destroyed at once, you'll end up with
>>>> weakened or necrotic tissue and potentially a carbuncle or open sore.
>>>>
>>>> If you're *really* unlucky, the anti-GFP reaction will cause an
>>>> autoimmune cross-reaction against a normal cell antigen, and you'll
>>>> develop something like Lupus. But I'll grant you that for GFP, that's
>>>> pretty unlikely! I doubt anti-GFP antibodies/TCAs resemble
>>>> anti-anything-else-in-the-human-body.
>>>>
>>>> On 01/01/14 21:26, Nathan McCorkle wrote:
>>>> > Realistically though, would the immune reaction be more than something
>>>> > like a bee-sting causes? GFP isn't an enzyme like bee-toxin is, just a
>>>> > non-self protein. Maybe a more similar allergenic situation would be a
>>>> > skin-allergen prick test.
>>>> > http://en.wikipedia.org/wiki/Skin_allergy_test
>>>> >
>>>> > On Wed, Jan 1, 2014 at 12:38 PM, Pieter <pieterva...@gmail.com> wrote:
>>>> >> I was shown the same picture, and share your skepticism. It seems
>>>> >> pretty
>>>> >> unlikely, and not documented elsewhere...
>>>> >>
>>>> >>
>>>> >> On Tuesday, 31 December 2013 20:00:38 UTC+1, Cathal Garvey (Phone)
>>>> >> wrote:
>>>> >>>
>>>> >>> Also, I have seen a phonecam shot of an alleged GFP "tattoo" where
>>>> >>> someone
>>>> >>> jabbed themselves with an Adenoviral gfp vector. I say "Alleged"
>>>> >>> because I
>>>> >>> can't imagine that working for more than an hour or so before going
>>>> >>> necrotic
>>>> >>> from immune rejection.
>>>> >>>
>>>> >>> Nathan McCorkle <nmz...@gmail.com> wrote:
>>>> >>>>
>>>> >>>>
>>>> >>>> On Dec 30, 2013 10:10 PM, "Patrik D&apos;haeseleer"
>>>> >>>> <pat...@gmail.com>
>>>> >>>> wrote:
>>>> >>>>> I bet it's only a matter of time before someone tries to give
>>>> >>>>> themselves
>>>> >>>>> a GFP tattoo with a gene gun though...
>>>> >>>>>
>>>> >>>>
>>>> >>>> That's already started happening, at least academically:
>>>> >>>> http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2855251/
>>>> >>>
>>>> >>>
>>>> >>> --
>>>> >>> Sent from my Android device with K-9 Mail. Please excuse my brevity.
>>>> >>
>>>> >> --
>>>> >> -- You received this message because you are subscribed to the Google
>>>> >> Groups
>>>> >> DIYbio group. To post to this group, send email to
>>>> >> diy...@googlegroups.com.
>>>> >> To unsubscribe from this group, send email to
>>>> >> diybio+un...@googlegroups.com. For more options, visit this group at
>>>> >> https://groups.google.com/d/forum/diybio?hl=en
>>>> >> Learn more at www.diybio.org
>>>> >> ---
>>>> >> You received this message because you are subscribed to the Google
>>>> >> Groups
>>>> >> "DIYbio" group.
>>>> >> To unsubscribe from this group and stop receiving emails from it,
>>>> >> send an
>>>> >> email to diybio+un...@googlegroups.com.
>>>> >> To post to this group, send email to diy...@googlegroups.com.
>>>> >> Visit this group at http://groups.google.com/group/diybio.
>>>> >> To view this discussion on the web visit
>>>> >>
>>>> >> https://groups.google.com/d/msgid/diybio/89d989d3-f0d5-41ea-838e-2c3aa47a3e61%40googlegroups.com.
>>>> >>
>>>> >> For more options, visit https://groups.google.com/groups/opt_out.
>>>> >
>>>> >
>>>> >
>>>
>>> --
>>> -- You received this message because you are subscribed to the Google
>>> Groups DIYbio group. To post to this group, send email to
>>> diy...@googlegroups.com. To unsubscribe from this group, send email to
>>> diybio+un...@googlegroups.com. For more options, visit this group at
>>> https://groups.google.com/d/forum/diybio?hl=en
>>> Learn more at www.diybio.org
>>> ---
>>> You received this message because you are subscribed to a topic in the
>>> Google Groups "DIYbio" group.
>>> To unsubscribe from this topic, visit
>>> https://groups.google.com/d/topic/diybio/wKFyweKjaro/unsubscribe.
>>> To unsubscribe from this group and all its topics, send an email to
>>> diybio+un...@googlegroups.com.
>>>
>>> To post to this group, send email to diy...@googlegroups.com.
>>> Visit this group at http://groups.google.com/group/diybio.
>>> To view this discussion on the web visit
>>> https://groups.google.com/d/msgid/diybio/482a471d-c746-4831-adf9-a115b8166d93%40googlegroups.com.
>>>
>>> For more options, visit https://groups.google.com/groups/opt_out.
>>
>>
>
> --
> -- You received this message because you are subscribed to the Google Groups
> DIYbio group. To post to this group, send email to diy...@googlegroups.com.
> To unsubscribe from this group, send email to
> diybio+un...@googlegroups.com. For more options, visit this group at
> https://groups.google.com/d/forum/diybio?hl=en
> Learn more at www.diybio.org
> ---
> You received this message because you are subscribed to the Google Groups
> "DIYbio" group.
> To unsubscribe from this group and stop receiving emails from it, send an
> email to diybio+un...@googlegroups.com.
> To post to this group, send email to diy...@googlegroups.com.
> Visit this group at http://groups.google.com/group/diybio.
> To view this discussion on the web visit
> https://groups.google.com/d/msgid/diybio/CAGHxOnRvK05pmTR1otf%3Dtk9KaON0cNFa6j-Xna2%3DoiGMQfjcgA%40mail.gmail.com.
>
> For more options, visit https://groups.google.com/groups/opt_out.



--
-Nathan