Today is Immunology Tuesday, and I thought I'd kick things off with some microbiology which will segue nicely into today's topic: complement. Friday's topic is going to be intercellular signaling, so that comes together nicely, I think.
I thought I'd begin with a lovely blog I stumbled on, courtesy of erv, also of SciBlogs. He seems to take a pathogenic approach to immunology. I've seen a couple of different approaches besides that, mainly specific functions of cells and regulation of gene expression. His blog's name is We Beasties, which always makes me smile.
Last semester I attended a microbiology seminar (to my chagrin I cannot find the seminar details, and so sadly cannot direct you to the gentleman's site) led by a wonderfully jovial speaker who did research into microbial genome plasticity. He knew he was addressing an audience of students and faculty, so he spent a good 15 of his 45 minutes talking about some basics in microbiology. He talked about some of the diverse forms, functions, and environments of prokaryotes, and the fact that we are made up of more prokaryote DNA than we are human DNA. Interesting concept.
Typical labs tend to coddle and spoil their colonies of microbes, simply in order to keep enough specimens alive for whatever purpose. He opted to starve his colonies of E.coli and see what resulted. This means that no additional nutrients were added to the plates or broth used to culture the colonies. To his great surprise, a number of things came up. For one thing, colonies hit the death phase of microbial growth, which resulted in about 98% dieoff, and then the colony recovered. The growth remained pretty steady after that.
Another unexpected outcome (although in retrospect perhaps not) came from an experiment they conducted where, after the death phase, colonies from 1 day old cultures were plated with 10 day old cultures. And the older colonies outcompeted the younger ones. Why might that be? Probably because they'd had more time to allow mutations to spread through the colony.
And my were there a LOT of mutations! Some of the most bizarre looking organisms came from this experiment. E. coli with long filaments, odd shapes, and even enormous sizes were found. The large cells were curious. In a starvation situation, it makes sense to try and get small, because you don't require as much nutrition to survive. But the researchers postulated that perhaps the large cells were able to out compete their smaller neighbors (though if they'd found evidence of phagocytosis they'd probably have the Nobel by now).
Analysis of the genome before and after the death and steady state phases revealed dropped segments of unnecessary genes, upregulation of metabolic genes that helped the bacteria process what little nutrition there was available, and an overall massive genome plasticity.
This seminar was really incredible. And one of the things that I might like to study in grad school is how the genome changes in starvation conditions and with exposure to low levels (as in, mortality less than 100%) of antibiotics. Also, I'm pretty sure that E. coli were chosen because they are hardy and easy to cultivate. I might like to look at more pathogenic and more fragile species that are more difficult to cultivate. If there is one thing I learned from this experiment and a semester of medical microbiology, though, it is that bacteria are tough little critters.
Moving on from microbiology, we come to our immunology topic for today: complement. Complement is amazing because it isn't even a finely honed system of cellular responses. Complement is a system of molecules. That's it.
Complement is considered part of the non-specific (or innate) immunity, because it does not generate a specific response depending on the type of pathogenic attack, and does not adapt itself to different types of immune stress. It is consistently synthesized and distributed and is the very first responder when the mechanical defenses of the immune system are bypassed.
Complement precursors are synthesized by the liver and white blood cells that are resident in tissue, such as macrophages and neutrophils, and circulates through the bloodstream.When activated (typically about 5-10 minutes after infection is detected) it is cleaved in a series of enzymatic reactions. The type of cleavage and the enzymes used in the reaction are dependent on the type of infection.
There are three pathways to complement activation. The classical pathway (so named because it was discovered first), the alternative pathway (probably discovered second) and the mannose-binding lectin pathway (so named because it reacts to a specific sugar on the outer coat of certain pathogens) all come to make their own variant of C3 convertase, which kicks off the cascade, but diverge depending on the series of proteolytic cleavages.
Stay tuned for part 2!
References:
Janeway’s Immunobiology, 7th edition by Murphy, Travers, and Walport. Garland Publishing, 2008
Medical Microbiology, 6th edition by Murray, Rosenthal, and Pfaller. Elsevier/Mosby, 2009
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