A new research paper shows evidence that immunization with devil facial tumor cells plus adjuvants (i.e. immune stimulators) primes anti-tumor immune responses. Subsequent booster shots with live tumor cells induced tumor regressions in 3/5 devils.
This new publication shows that the key immune checkpoint molecule PD-L1 (aka B7-H1) is upregulated on devil facial tumour cells in response to interferon-gamma (IFNg). This could be an important immune evasion mechanism used by the tumour to shut off anti-tumour responses by T cells and NK cells.
Wild Immunity research published in Functional Ecology is featured in Smithsonian magazine.
In the past few years I have heard several people say that Tasmanian devils, the animal I am studying for my postdoctoral research, have the strongest bite force of any animal. Interestingly, I have also heard many people say that spotted hyenas, the animal I studied during my Ph.D. research, have the strongest bite for of any animal. Clearly something must give. I will give the devil its due by saying that maybe devils have pound-for-pound the strongest bite, but I have no evidence to back this up. In fact, I doubt that anybody has real evidence to back up their claims about animal bite force.
A former PhD student on the MSU Hyena Research Project actually tried to measure the bite force of hyenas, but they would usually just nibble on the bite force tester, and thus the test isn’t valid. It comes down to a problem of motivation. I suspect that the only time a hyena uses its full jaw strength is when it is cracking open large bones to eat the nutritious bone marrow inside. Hyenas have been known to crack open giraffe femurs, and there is no way that a devil could do that. Check back later for my thoughts about why eating bone marrow would be good for the hyena immune system.
If I had to guess which animal actually has the strongest bite force, I would guess an elephant. They literally eat trees. I wouldn’t put my hand in an elephant’s mouth. This finally brings us to the actual topic of this post, how to get blood from a hyena. The research I did to earn my Ph.D. was focused on understanding how spotted hyenas do everything wrong when it comes to getting sick (i.e. eating rotten carcasses, live in large social groups, fight…), but somehow rarely get sick and almost never die of disease as far as I can tell. The most common causes of death for wild hyenas are lions, people, and crocodiles. In order to begin understanding the immune system of hyenas, it was necessary to get blood from hyenas.
So how do you get blood from an animal that can bite your hand off? You use an air rifle to shoot the hyena with a plastic dart filled with an anaesthetic. Click this MSUToday: Learning about hyenas link for a short video about darting a hyena and the measurements and samples we get from the hyena after we dart it. Some of you may recognize the shooter, but mostly you will want to pay attention to my Ph.D. supervisor, University Distiguished Professor and National Academy of the Sciences member Kay Holekamp. She has been running the MSU Hyena Research Project since 1988. If you want to know something about hyenas, she is the person to ask. Actually, she is a very good person to ask about many topics in biology and science in general.
One thing that people are often very surprised to learn is that hyenas are actually more closely related to cats than dogs. This is so surprising that even my idol David Attenborough got it wrong in his Life of Mammals documentary. I was also sceptical about this little known hyena fact the first time I heard it, but I have actually confirmed hyena-cat-dog relationship in my own research looking at how the hyena immune system detects potential pathogen. I sequenced the DNA for a group of immune receptors called toll-like receptors (TLRs) and found that the DNA for all 10 of the hyena TLRs that I sequenced was more similar to cat DNA than to dog DNA. See table 2 in Characterization of toll-like receptors 1-10 in spotted hyenas for further details. Check back soon to see latest Wild Immunity research on hyenas which will be published in PloS ONE in October, 2015.
Question of the day:
The MSU Hyena Project Research blog has been going since 2008 and is loaded with great stories from the field!
Encyclopedia of Life: Spotted hyena
Check out a nice video from Smarter Every Day on the Tasmanian devil facial tumor disease. Most of the people in the video, except the host, are my new colleagues at the Menzies Research Institute Tasmania.
At first glance sponges may look like the most helpless animals on the planet, simply drifting with the ocean currents with no means of changing course or defending themselves. Sponges have no arms or legs for moving themselves around, no eyes or other obvious sense organs, and nothing that most people would consider a brain. Without any of the tools (i.e. big brains, opposable thumbs, bipedal walking, etc.) that helped modern humans spread across the planet, sponges have been floating around the earth for at least 500 million years.
One of the main themes of Wild Immunity is that every living thing on the planet needs to defend itself against exploitation. So how have the seemingly helpless waifs that we call sponges managed to defend themselves? One extremely effective defense system that sponges use is the complement system (reviewed by Leslie, 2012). No, they don’t whisper sweet compliments to their would-be parasites and convince the potential disease causing agents to attack something else. The complement system is set of proteins that work together to kill or disable pathogens. The complement system has proven so effective at neutralizing microorganisms, such as bacteria, that the system has been conserved across hundreds of millions of years of evolution, and there are clear similarities between complement proteins found in sponges and humans (reviewed by Leslie, 2012).
In the late 1800s it was discovered that blood serum could kill bacteria. The next discovery was that some of the bacterial-killing capacity of serum could be destroyed by heating the serum. The term complement was coined by Paul Ehrlich to describe this “heat-labile” component of serum. Since then, the system has been extensively studied and roughly 30 proteins have been identified that play a role in the mammalian complement system, and complement protein homologues (evolutionary-related proteins) have been found in nearly all animals, including sponges.
How it works
There are several different pathways (classical, alternative, and lectin-binding) that the complement system uses to kill bacteria, but all three pathways are dependent on the formation of a C3-convertase, which cleaves C3 into C3a and C3b and kicks-off of a cascade that cleaves other proteins into active forms. The end-product is a membrane attack complex formed by C5b, C6, C7, C8, and C9 that pokes a hole in the bacterial cell membrane, causing the bacterial cell to lose its ability to maintain homeostasis and die. Specialized immune cells called phagocytes then detect the complement proteins bound to the bacterial products and clean up the mess.
More than just a bacteria killer
Complement is such an effective and ubiquitous defender against microorganisms, that many pathogens have evolved proteins that attempt to disable complement. For example, the deadly variola virus (aka smallpox) produced proteins that bind to and disable C4b and C3b. In addition to complement prowess as a defender of homeostasis, over the past few decades it has become increasingly clear that complement is integrated into many aspects of immune defenses and general physiology. In addition to its important task of killing bacteria, it also helps neutralize viruses and parasitic worms, clears dead host cells, form new blood vessels, generate new tissue following injury, and direct formation of new neuronal synapses (Ricklin et al., 2010). Defects in complement genes have been associated with many diseases, such as cancer and lupus (Madelson, et al., 2004), and research is rapidly uncovering new roles for complement. The short version of this story is that the complement system has been critical for survival for millions of animals for millions of years, and still has important and diverse roles in health and disease today.
Question of the week
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Encyclopedia of Life: Sponges
Leslie, M., 2012. The New View of Complement. Science 337, 1034-1037.
Manderson, A.P., Botto, M., Walport, M.J., 2004. The role of complement in the development of systemic lupus erythematosus. Annu. Rev. Immunol. 22, 431–456
Ricklin, D., Hajishengallis, G., Yang, K., Lambris, J.D., 2010. Complement: a key system for immune surveillance and homeostasis. Nat Immunol 11, 785-797.