Tag Archives: Immunology

Working Hard to Stand Still; Or “COME THROUGH, IMMUNOCYTE!”

A dear friend of mine who is an intrepid post-doctoral researcher in the often murky, and full of much flow cytometry field of haematopoiesis sent me the following text from a recent gathering of some of the foremost immunologists in the field:

“People are now realizing that nutrition and immune function are closely linked. What a shocker!”

My friend comes from a nutritional biochemistry background, so this idea that the abilities of one’s immunocytes are closely linked to what you put in your body wasn’t especially mind-blowing to her. However, I could see why this could be so for others.

See, we think of the immune system as something that fights, kills, protects. It’s almost as if these cells are divorced from any other roles. However, that mindset is changing. And why not? The immunocytes in our body are inspiring: they make a variety of different pleiotropic factors, they are activated by many, many ligands/metabolites, they network with multifarious cell types like it was their job (it kinda is!), and so why wouldn’t they be involved in—wait for it—homeostasis?!

Because immune cells recognise that host defence and homeostasis are different games. Both of which they play well!

I recently read a piece about how γδ T-cells rely on recognizing metabolites from the mevalonate pathway to recognise rapidly proliferating cells—potential tumours—and kill them, thereby exerting tumour control. Inflammatory events are involved in the regulation of insulin responses and obesity. Phagocytes and  a class of Treg cells regulate homeostatic responses and prevent autoimmunity and pathology at the level of the skin. Innate lymphoid cell classes provide a protection against immunosuppression and subsequent bacterial infections in the gut by modulating their functions under conditions of nutrient depletion. Interferon γ, that paragon of antiviral responses, also helps out in maintaining skin pigmentation. Alternatively-activated macrophages show up, and help regenerate muscle after acute muscle damage (think: exercise).

Immune cells: working hard so things “stand still.”

Why am I sharing these examples? Etymology tells us that “homoestasis” means “standing still.” We think of immunocytes as warriors, not a meditative, “standing still” population. That they do the legwork in processes that enable “standing still” can be thought of as, in a way, prophylactic. Immunocytes would seemingly be involved in making sure that things remain normal, happy and homeostatic rather than mobilizing a big immune response if/when something goes even slightly wrong, physiologically speaking. This makes sense because launching an immune response is costly to the body. In many ways, it is like going to war. Your legions of immunocytes are your troops, you have to feed them, keep them functional. This is energetically expensive, and makes you feel like crud most of the time. So why not ensure that things “stand still” rather than deal with hourly fresh Hells of physiological dysregulation?

To put it another way: the immune response will turn up when needed, but have you ever partied for 4 days straight, and then gone on a weekend binge? Hurts, don’t it? Turn up, and be legendary rather than being in a constitutive state of turnt! 🙂

Take care,

A.

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My Project, Myself

My project and I? We’re in a good place. We don’t hate each other. This isn’t like the Eminem-Rihanna thing that had begun to happen with my MS thesis. Oh, Lord. Those were dark, drunk days…

I will admit, I was a bit calculative when I picked my current lab: we work with NKT cells, a flavour of immunocyte that isn’t completely understood. Thus, there is a lot to do, lots of questions to ask, lots to answer, and lots of new questions to raise….However, real-talk: I don’t get these cells. I don’t understand them. I don’t understand where their so-called “self” antigens come from. I don’t understand how they get to, y’know, BE. This doesn’t bother me, though, because I imagine that this is part of the process of getting this here PhD. If I knew this already, why in the world would I be in the lab setting up experiments?

My work focuses on the adhesion and migration behaviour of NKT cells in response to differential integrin signaling. The project was born out of this brilliant paper by Dr. Seddon Thomas, whom I admire from afar. In truth, we don’t know what makes NKT cells wanna travel, and if they do, where do they go? Dr. Thomas’s work seems to suggest that NKT cells home to the sinusoids of the liver given the high concentration of ICAM-1 there. I’ll buy it. The paper also suggests that PLZF (zinc-finger protein, transcription factor, controller of cell cycles and fates) is the key regulator of LFA-1 abundance on the NKT cell surface. Sounds good to me…mainly because it opens up all these avenues for the impact of NKT chemokine and integrin/receptor profiles on pathogenesis of inflammatory diseases.

NKT cells are a big deal in asthma. So, what causes them to home to or away from the lung? Is PLZF responsible, again? There are other things. Things I am not at liberty to speak of, but, needless to say, am chuffed about.

So, here we are: my project and I, eyeing each other gingerly, wondering what shall happen next…

Take care now,

A.


T-Cell Biology and The Young Experimental Scientist

So, I might be a little rusty. I haven’t blogged for myself in a while. My last blog was a sensationalized and very public diary of the rather sordid goings-on of my undergrad days in a very snowy, very Midwestern city– but none of that is of any consequence. Those who peopled those stories have now found spin-offs and supporting roles elsewhere. This blog is not about them. This blog is not even about me. Well, it is, but this blog is about me and the adaptive immune system, me and graduate school, and T-cells. There will always be T-cells.

Now, immunology and I: we go way back. Think 9th grade. Or was it the eighth? Who knows anymore? But, I remember making a series of holes in the worn cloth of my pencil-case imagining that the “ancient proteins that punched holes in bacteria” operated on a similar principle. There were also cells: T-cells killed, B-cells made antibodies, macrophages pigged out like jocks during football season while neutrophils, like extras from “The Devil Wears Prada” sleekly extravasated where damage control was needed. For me, that might have been the first time I wondered how? That a lot of that wasn’t quite known at the time was also exhilarating. But, I had med-school dreams: the mysteries of the immune system, esoteric as they were, were someone else’s problem.

It was during my undergrad, however, that immunology and I met again. Both of us were  older: immunology, suffuse with brand-new cytokines and transcription factors, and I awash in discovering how wonderful it was to have an open mind. Under the tutelage of a Bright Young Thing of the immunology firmament, I began to rediscover the hows that were not known when I was a ninth grader. Sound as those unknowns were, they led to newer questions. There were worlds to discover within!

What attracted me to T-cell biology more than anything else was the sense of precision, control and extroversion (if you will!) that T-cells inherently posses. In my mind, CD4+ T-cells would receive antigens (only peptides, linearised, of a precise amino-acid length and loaded onto the right kind of MHC molecule, thanks) like aristocrats languidly snatching up a letter from a tray. If the contents of the letter were of importance, these cells would snap to action: proliferate and home to the site where they were needed to direct traffic, all the while secreting cytokines with abandon, like mass texts announcing a rager of a party, recruiting more of their own and sending messages of intent or disfavour to other cells. All of them, united towards a common goal of eliminating a threat or, in more misguided cases, the self. The immune response, in the best and the worst cases, is a grandiose production, a symphony of activated cells whose cytosols, like metropolitan roads at rush hour, are inundated with proteins passing phosphoryl groups from one to the other, all the way down to the nucleus…and there are so many of these cells, their orchestrations under masterful control by CD4+ T-cells.  I am breathless thinking about it.

And so, this is the idea behind the blog: to articulate the awe I feel about adaptive cells and the cells that are intermediaries in the “Upstairs/Downstairs” situation that exists between the innate and the adaptive arms of the immune system.  As I talk to you, constant reader, I myself understand more, and everybody wins!

Take care now,

A.