I think a lot of kids get the wrong impression about the medical field via TV. I mean like, I like ‘House’. It is an entertaining TV show. But being an MD is absolutely nothing like that. Its not really a mystery novel. Its more like ‘cataract surgery 5 times today… and 15 times this week… yaaay…’ and ‘pap smears and prescriptions for yeast infections and UTIs all day… yaaay…’
So when I had an opportunity as a ‘pre-med’ to do summer research, it blew mah mind!!!! Everything everyone was working on was like a little specialized mystery novel. It was both fun and frustrating, and I felt like I was using every neuron in my brain to solve my ‘mystery’ for the summer. And you didnt just have to be ‘smart’ (hell, you really didnt even have to be ‘smart’)– you had to be MacGyver/Sherlock Holmes/Professor Layton smart. Notice the importance of things other people think are insignificant, see patterns in everything, make what you have do what you need.
Its one of the main reasons I ditched med school for grad school.
I just learned about a friggen sweet mystery in virology: Chikungunya virus.
Theres nothing mysterious about the virus itself. (+)ssRNA. Enveloped. Likes macrophages. Transmitted by mosquitos. When a human gets infected they have the usual viral symptoms (headache, muscle aches, fatigue) plus a massive fever (104 F) and ‘incapacitating’ joint pain. Like, on that pain scale, 0-10, people report ~8. :-/
Good news is, this virus doesnt kill you. The younger you are, the faster you will get better (young ones get better in less than 2 weeks, elderly need months/years…).
Heres the mystery: Some people get better, but months later, get the joint pain again. And then they get better. And then joint pain. And then they get better. Over and over and over.
Whats up with that?
There are some obvious answers.
1– The virus is still there. The people with chronic CHIKV may appear ‘better’, but they really arent better.
Nope. If you look in these folks blood during acute infection, there can be 20,000,000,000 viruses/ml of blood. :-/ When you test them once they get ‘better’… there is no virus, there are no infected cells.
Furthermore, even though all patients make antibodies and cytotoxic T-cells that recognize CHIKV, your adaptive immune system isnt really necessary to clear the infection. You can totally knock out that branch of the immune system in mice, infect them, and they can still get better. Humans usually clean up the virus before your adaptive immune response can even mature in response to CHIKV. And we know the antibodies people make are ‘good’– if you take antibodies from a recently recovered patient and give them to mice, and then challenge the mice with virus, the mice dont get sick. So antibodies and CTLs should be cleaning up any potential virus that might still be lingering around.
2– The antibodies are the problem. CHIKV leads to the development of autoimmunity that targets something in the joints.
Nope. No one can find auto-antibodies in chronic patients.
Turns out neither one of these wrong answers are totally wrong!
Persistent chronic inflammation and infection by Chikungunya arthritogenic alphavirus in spite of a robust host immune response
Heres what happens– People get infected. They get a huge immune response to the virus. The virus goes away. Their immune system goes back to normal…
Except in people who have the chronic disease, the virus doesnt really go away, and their immune system doesnt really go back to normal. One of the tell-tale signs was that even though immune cell counts went back to normal after acute infection, a couple of chemical messengers, IL-12 and INF-a, stayed elevated. IL-12 is a sign of inflammation. IFN-a is a sign of viral infection.
So these researchers went straight to the point– they took biopsies of the joints of people who had this chronic joint pain (the biopsies were for other purposes– too invasive to do them ‘just to see’). Even though systemically there was no virus, and immune cells were normal, in the joints shit was still going down!
There was virus, there was a ton of inflammation, tons of infected cells.
Look at the whole patient: Everything looks fine.
Look at the joint: AAAAAAAHHHHHH!!!!!
Well, that solves that mystery! Hurray!!
… but it opens up a whole new mystery novel. How the hell is this infection staying localized at the joints??? Joints are not immune privileged. These people make neutralizing antibodies, why arent they helping? These people make CTLs that target infected cells, why arent they helping? Why isnt the entire body responding to this localized infection????
Further avenues of research.