Tag Archives: Immune system

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,


Worm Me!

I cut my teeth on allergy and asthma. For my M.S., I worked in a lab that looked at hypersensitivity to Aspergillus fumigatus, a pretty common mold whose star has risen as a potential invasive/infectious disease biggie in our largely immunosuppressed world. My work concentrated on the allergenic prowess of A.fumigatus, however, and I looked more at systemic pathology rather than any particular cell-type or mediator. Of course, pathology in allergic disease is under the control of many cell types and their assorted secreted nasties, and those, in turn, are directed by cytokines secreted by CD4+ T-cells.

Now, an allergy is a propensity to an inappropriate, aberrant immune response to something that doesn’t quite warrant it. Peanuts, dander and pollen are meant to be enjoyed, brushed away…and, gee, I don’t know what one does with pollen…In allergic individuals, however, these seemingly innocuous antigens elicit a strong, inflammatory immune response, characterised by high titers of IgE, eosinophilia and the presence of hallmark Th2 cytokines like IL-4, IL-5, IL-13, IL-33, SCF and TSLP. Given that Th2 refers to a type of T-helper (type 2, specifically) response, one has to wonder why the usually on-point, meticulous T-cell has such an overreaction to Elizabeth Barrett Browning’s (which is what I would name my cat) dander.

The Hygiene Hypothesis offers an explanation. My understanding of this is that a clean, sanitary lifestyle somehow predisposes the immune system to act out against a non-immunostimulatory antigen. Now immune systems that develop in unsanitary strife of a variety of irritants and potential pathogens learn quickly to deal, and respond only to potentially problematic antigens.

Fair enough.

However, the Extended Hygiene Hypothesis takes a larger picture view of the same idea wherein it claims that the composition of gut microbes in children as well childhood infections to worms, for example, eventually influence the inflammatory response. This becomes important because it is the prevalence of chronic inflammation that unites the ostensibly different disorders of allergic asthma, atopic dermatitis, type 2 diabetes and, wait for it, depression. The Extended Hygiene Hypothesis states that early exposure to a more diverse microbial population will bring forth a worldlier immune system that shall not freak out any time the status quo is changed, thus, less allergies, and inflammation that does not overstay its welcome.

A vote in support of the above is seen in da Costa et al’s study “Schistosoma mansoni-Mediated Suppression of Allergic Airway Inflammation Requires Patency and Foxp3+ Treg Cells” published in PLoS Neglected Tropical Diseases on August 15th, 2013. The study is strong proof for the Bystander Suppression phenomenon wherein the immune response to worm antigens suppresses the similar immune response made to OVA allergen. This, to me, is a powerful observation since it gives us a glimpse into the “priorities” of the immune system, as it were. The immune system goes back to basics when faced with both an allergen and a pathogen: after all, the Th2 response evolved to deal with metazoan parasites.

Further, the authors also uncover a new putative mechanism by which suppression of airway inflammation is mediated: via T-reg cells. Foxp3+ve, CD4+ve T-cells, or regulatory T-cells are the effective voice of reason during inflammation, the voice that goes, “Shut it down!” to cells that are cranking out inflammatory factors with wild abandon. Obvious as this may seem now, as da Costa et al say, the silencing of airway inflammation has, classically, been the prerogative of regulatory B-cells and that eternal pacifist, IL-10.

So, is the worm the answer? Is it the intermediary that needs to be reintroduced into the equation so that different T-cell populations can talk and abrogate allergic inflammation? Apparently, this is a thing. It’s not as unorthodox if it sounds if research manages to unearth immunostimulatory components from worms that act as the Rosetta Stone of cytokinic communication between cell types and, ultimately, reduce allergy altogether. Could we be headed towards an age where any child who yearns for a pet is reminded that s/he bears a symbiont worm within?

Stranger things have happened. 🙂

Take care now,


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,