Category Archives: Microbes

Laveran’s eye

The military hospital of Constantine, Algeria was a fitting place to view what must have seemed the Devil in microscopic form.

Stages of the malaria parasite drawn by Alphonse Laveran

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.

War or Police metaphor in immunology?

Immune modeling

I am concerned about the use of the police and war metaphor in immunology; you can have a look at my previous post. I find it very difficult to think outside of this specific box. We are taught immunology with this metaphor. We told to communicate about immunology with this metaphor. I have the feeling that I face a wall when I try to think differently.

When you try to avoid the political extremism of this metaphor, it is difficult not to go into an other extreme, into a caricature of the opposite position. Indeed, we could be tempted by a peace and love metaphor (ref 1), but this would  be such a caricature.

I chose here to take a political direction to give an example of a way to rethink the metaphor. I agree that science should avoid politics. But today for the sake of thinking outside of the…

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Which metaphors for immunology?

Immune modeling

Many good articles have been published on the use of metaphor in science and in particular in biology (ref 1&2).

I will try to sum up a few questions about the metaphors used in immunology following the discussion of the conference given by Michel Morange at IHPST.

First, what are the metaphors used?

– The metaphor of the immune system being endowed with the mission of a police, or to make war : Indeed words such as “defence”, “attack”, etc…. are very frequently used. Even if immunologist will answer that they are aware that it is a metaphor, I am worried about the effect of such large use. Even if the metaphor may be discussed by the community, this does not appear to the general public that is only exposed to this war or police metaphor. One example shows that it is even the way of presenting immunology that is…

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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.

Phylogenetic humility

Just a welcoming sentiment from Robert M. Sapolsky in his collection of science essays, Monkeyluv. Sapolsky is a professor of biology and neurology at Stanford, and his essays, often humorous, delve into neuroscience, hormones, and human behavior. Oliver Sacks has called him “one of the best scientist-writers of our time,” and while I wouldn’t put Sapolsky on the same pedestal as I do Gould, or Levi, or Thomas when it comes to prose and insight, the man certainly has his moments, which manifest in me dog-earring a corner of a page. This one stood out to me this morning on the 3 train to work while reading an essay titled ” Bugs on the Brain.” As someone who gets excited over pathogenic protozoa and animal behavior, I muttered “Toxoplasma gondii” upon seeing the heading.

Like most people who come across any mention of Toxoplasma (it gets a fair amount of press; e.g., via Carl Zimmer), Sapolsky is interested in the precision of how the protozoa can manipulate behavior. The organism relies on a simple and common two-host system to complete its life cycle: the predator-prey interaction of rodent and cat. Rodents ingest the protozoa, which encysts in the mammal, with particular affinity for denning in the brain. When rodents are consumed by felines, Toxoplasma can reproduce, new organisms are shed through feces, which happen to be a food source for rodents and thus how the life cycle comes full circle. Many pathogens that rely on multiple hosts influence behavior, and there is a bevy of literature that describes just this, particularly with tapeworms. In the case of Toxoplasma, the protozoa interferes with a rodent’s natural aversion to feline pheromones; interferes is a weak term–the organism makes the rodent attracted to feline odor, increasing the probability that it becomes successful prey.

What interests Sapolsky so about this host-parasite interaction is that a rodent infected with Toxoplasma gondii otherwise behaves normally. As he notes, infected rodents maintain their social status within the system’s hierarchy, they continue to mate and thus sense pheromones of the opposite sex, and their recognition of other vertebrate odors isn’t tampered with in the least. The protzoa is simply able to manipulate the recognition of and reaction to the pheromones of one predator, that of the definitive host. To Sapolsky (and most of us interested in the long-term interplay between parasites and their host), this is evidence of how counter-intuitive and beautiful evolutionary process can be. Sapolsky takes the opportunity to highlight Toxoplasma gondii as a correction to teleological interpretations of evolution: its processes aren’t directional, aren’t progressive.  As he notes, “We are certainly not the most evolved species around, nor the least vulnerable. Nor the cleverest.” But the punctum of his message, to borrow a term from Roland Barthes (that which “pierces” the viewer/reader), is the statement, “we need phylogenetic humility.”

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.