Tag Archives: immunology

Lives of muskrat lymphocytes

Large lymphocyte from a normal blood film

One of my favorite essays by the immunologist-poet, Miroslav Holub, describes the symphony of cellular life enacted after a muskrat drowns in the writer’s pool and is shot by a neighbor. The scene itself is grim yet fairly boring and commonplace; dead animals, be it a robin flown into our window or a white-footed mouse decapitated by our cat, seem to be an ordinary part of suburban life. But Holub views the situation from the interior view of the animal and with the sense and extrapolation of a poet. His interest in the phenomenon of death lies in the cellular process that are taking place long after we conceive of the animal as “dead.” While ordinarily we see the spectrum of alive to dead as having a definitive moment of change from A to B, a universe of interactions, an ecosystem of cellular bodies, continues to communicate, move, exist. I’ve copied my favorite excerpt from the essay, that of the lymphocytes (an immunologist’s specialty), below.

So there was this muskrattish courage, an elemental bravery transcending life.

But mainly, among the denaturing proteins and the disintegrating peptide chains, the white blood cells lived, really lived, as anyone knows who has ever peeked into a microscope, or anyone knows who remembers how live tissue cells were grown from a sausage in a Cambridge laboratory (the sausage having certainly gone through a longer funereal procedure than blood that is still flowing). There were these shipwrecked white blood cells in the cooling ocean, millions and billions of them on the concrete, on the rags, in the wrung-out murkiness. Bewildered by the unusual temperature and salt concentration, lacking unified signals and gentle ripples of the vascular endothelium, they were nevertheless alive and searching for whatever they were destined to search for. The T lymphocytes were using their receptors to distinguish the muskrat’s self markers from nonself bodies. The B lymphocytes were using their antibody molecules to pick up everything the muskrat had learned about the outer world in the course of its evolution. Plasma cells were dropping antibodies in various places. Phagocyte cells were creeping like amoebas on the bottom of the pool, releasing their digestive granules in an attempt to devour its infinite surface. And here and there a blast cell divided, creating two new, last cells.

British Lions

“When lions started speaking English, animal keepers were the only ones who could understand them. Others didn’t take the whole thing seriously – Wittgenstein famously said that if lions could talk, they would stop being lions. He didn’t clarify, however, if animal keepers would remain human, should they understand lions’ roaring.
On Sundays animal keepers and lions sit up straight at the round table in the local inn and, scarcely exchanging remarks, divide between them a huge Union Jack cake.”

– Anatoly Kudryavitsky

Where immunology and a poet meet

The other day I posted a poem written by the Czech immunologist/poet Miroslav Holub, who was said to be one of that country’s greatest poets of the century, as well as a well-published research scientist. In the preface to one of Holub’s collections of poems, Sagittal Section, Lewis Thomas, another biologist–poet, noted that Holub was composing what both scientists and poets filter everyday live for, those “points of connection between things in the world which seem to most people unconnected.”

October 21st, 1993, David Morley, an environmental scientist–turned lyric writer, interviewed Holub for roughly an hour about the immunologist’s thoughts on performing his poetry, the greater relationship between science and the arts, and the impact of the 20th century’s events in the Czech Republic on Holub’s writing. As a whole, the interview is a meditation on living between two worlds that inform each other in a reciprocal fashion. Holub’s words function as a subtle counter to those artist narratives of a solitarily focused creator, one whose life is the making of their craft and whose art is in turn their life.

The immunologist–poet allows instead a process, a space where exchange of idea and inspiration occur, where scientific discovery and lyric writing are neither mutually exclusive categories nor entirely dependent acts in the dance.  And yet as much as these two elements of Holub’s life inform his view of the world, they are not an all—there is more to life than work and production, Holub asserts. To take one’s self so seriously, to see their art or science as an absolutism, is to be a “workaholic,” a word the interviewee abhors in the English language. Instead, life should be about play, about a childhood sense of exploration and humility—Holub sees a different path. As he notes during the exchange, “I am serious about science, and I am serious about my poetry, but I do not take myself seriously.” Humbling words from a humbling man.

Find the full audio recording here.

Another parasitology blog

While on the topic of host-parasite interactions, I recommend looking through an interesting science research blog, The Parasite Diary. There’s a trend in the blogosphere toward “research blogging.” While most science blogs tend to discuss scientific research in some way or another, research blogging (www.researchblogging.org) aims specifically to discuss, in detail, and without lessening analytic rigor, the results of the peer-reviewed literature in a given field. The Parasite Diary takes this approach as pertains to classic parasitology: studies examining life cycles, pathogen interactions with the host immune system, systematics–in other words, a good deal of interesting lab-based research to examine life from the parasite’s point of view.

Metaphor of microglia: the maintenance amoeba of the brain’s neural network

[Here on out, eukaryography will have weekly or so examples and discussions of creative metaphors used by writers of scientific phenomena. Today’s imagery comes from Mo Costandi at Neurophilosophy]

It is said that the human brain contains roughly 10 billion neurons, each of which is connected to those other neurons through 10,000 synapses. This figure, massive as it may be, is also an understatement—Mo Costandi at The Guardian notes that in actuality the numbers come in closer at hundreds of billions of neurons and glial cells, those non-neuron cells—also known as neuroglia—that maintain homeostasis in the brain and provide support and protection of neurons. In turn, this quantity of cells produces more like  a quadrillion synapses.

To maintain some control over this complex information processing system, our brain generates more neurons and neuroglia than necessary, ensuring a surplus of connections. To reduce noise in this system, the brain relies on a process known as pruning. Also known as neuro-structural reassembly, pruning can occur through several interrelated scenarios. In one, the brain must replace simpler associations with a matured understanding of complex relationships—as we mature from childhood, our brain does as well, and needs reconsideration of the economy of neurons to do so. This process is part of the more general act of the network’s housekeeping. Neurons that have been damaged, are decaying, or are no longer necessary are removed to improve the overall functioning of the organ. Costandi writes that although neuroscience has know this process continues into and somewhat through our adult lives, the field has been in the dark in regards to the mechanisms—the how of X connecting to Y—of pruning. Costandi reports that now, a team of Italian researchers has been able to clarify this void in our understanding. Pruning, they have found, occurs through the actions of cells called microglia, which scour the developing human brain and engulf unnecessary synapses.

Microglial cell from the mouse brain expressing green fluorescent protein. Photograph by EMBL/ Rosa Paolicelli.

The microglia are related to the macrophages of the innate immune system, and functionally are very much the same. A variety of macrophages exist,  and their roles include ingesting foreign material, releasing cytokines to stimulate other macrophages, and presenting antigens. In the same way, microglia act as the initial defense against invading pathogens and substances and performing maintenance tasks. But Costandi doesn’t limit his definition of microglia to the vocabulary of immunology—he also draws on a personal favorite, that of protozoology. Microglia, he writes,

crawl, amoeba-like, through the spaces between neurons, using their protrusions to detect viruses and microbes that have infiltrated the brain and quickly engulf those they find.

Amoeba, members of the genus Amoeba, were discovered by early cell biology in 1757 by  entomologist August Johann Rösel von Rosenhof. In his Insecten-Belustigung (Recreation among the Insects),  Rösel described, sketched, and discovered that one species of these organisms, which he called “the little Proteus,” when touched, drew its octopus-like figure together.

Engraved colored figures of Volvox and amoeba, August Johann Rösel von Rosenhof (1757).

This form-changing ability, which became the characteristic of amoeba that gave the group its 18th century name, Proteus animalcule—after the Greek god Proteus, who could shift his shape—is an aspect that allows these organisms to feed. Amoeba have cytoplasmic extensions called pseudopodia that accout for this shape shifting–like imagery. This process is the prerequisite for phagocytosis, the act of engulfing other organisms or matter in the pseudopodia and bringing them into the amoeba’s body to be metabolized. This “cell eating” phenomenon is also exibited by the macrophages and microglia that Costandi notes in his article:

Phagocytosis means “cell-eating” and is the process by which microglia and other cells take up solid materials. First, the material is pulled towards the cell membrane, which then begins to invaginate, or fold in on itself, to envelop the material. As the in-folding continues, the outer edges of the membrane are drawn together until they eventually meet, producing a globule (the vesicle), which then buds off and moves into the cell. The contents of the vesicle are then processed appropriately—microbes are destroyed and membrane proteins and other cellular components recycled.

Below, an amoeba, Vannella sp., engulfs an unspecified cell through this meticulously described process.

And returning to the first part of the metaphor, that of the microglia-as-macrophage, in the following video a white blood cell chases bacteria through a maze of erythrocytes.

Through the experiment performed by Rosa Paolicelli et al.the details and methods of which are explained in full by Costandi at his Neurophilosophy blogmicroglia in the brain tissue of mice were found to be engulfing, in much the same way as an amoeba or macrophage, fragments of a protein known as PSD-95, which is major part of the protein network found in active synapses of the brain. In the following video from Nimmerjahn et al. (2005), we can visualize microglial cells patrolling synapses for functional deficits.

Therefore, Costandi writes, “the developing brain treats unwanted synapses as if they were unwanted invaders. It dispatches microglial cells to survey the state of synapses in their surroundings and to dispose of the ones that are wired incorrectly or superfluous.” To the microglia in our neural network, unnecessary and outdated synapses are akin to pathogens in the bloodstream, particles of algae to a grazing amoeba in a drop of lake water in Rösel’s German countryside.

“Immanuel Kant”

Immanuel Kant

The philosophy of white blood cells:
this is self,
this is nonself.
The starry sky of nonself,
perfectly mirrored
deep inside.
Immanuel Kant,
perfectly mirrored
deep inside.

And he knows nothing about it,
he is only afraid of drafts.
And he knows nothing about it,
though this is the critique
of pure reason.

Deep inside.

Miroslav Holub

Holub’s poetry

In the Microscope

Here too are the dreaming landscapes,
lunar, derelict.
Here too are the masses,
tillers of the soil.
And cells, fighters
who lay down their lives for a song.

Here too are cemeteries,
fame and snow.
And I hear the murmuring,
the revolt of immense estates.

– Miroslav Holub (1923-1998)