Not long after white blood cells were discovered, scientists like Rudolph Virchow and Paul Ehrlich pioneered their use as diagnostic tools. To this day, physicians use counts of white blood cells to identify infections and help diagnose hidden medical conditions. Such tests rely on the unique aptitude of leukocytes to detect invasive pathogens or other immune threats. But how great must a threat become before the cells can detect it? In other words, how sensitive are the white blood cells?
In recent collaborations with immunologists and clinicians of UC Davis, the Heinrich lab has carefully examined the response of single human neutrophils (the most abundant type of white blood cell) to real-world pathogens like Salmonella bacteria or Coccidioides fungi (the cause of Valley fever). The basic idea behind the experiments is straightforward: pick up an initially passive immune cell with a micropipette and arrange one-on-one encounters with a suitable target particle. To witness the ensuing battle is often a thrilling and highly satisfying experience. Instructive time-lapse videos of neutrophils in action can be enjoyed on YouTube or as part of the popular textbook “Molecular Biology of the Cell”.
Recently, an intriguing observation caught the attention of the Heinrich group. Under certain conditions, the immune cells were able to sense the presence of target particles before even touching them. In these cases, the neutrophil appeared to reach toward the target particle from a distance. By moving the target to different sides of the cell, the researchers triple-checked that the cell response was indeed specific to the nearby particle. But how does this chemotactic recognition work? What is it that the cells actually detect? Immunology textbooks offer a variety of answers to this question, often without clarifying which type of response is most relevant in a particular case. The UC Davis researchers have established that in the presence of donor serum, this recognition of both bacterial as well as fungal targets is predominantly mediated by small peptides called anaphylatoxins. These chemoattractant peptides do not originate from the pathogenic microbes themselves. Instead, special serum enzymes (assembled on the pathogen surface by the host’s complement system) produce and release the anaphylatoxins.
The Heinrich lab has soundly validated that even single human neutrophils can reliably report the presence of anaphylatoxins. Currently there seem to be no other techniques that can detect these chemicals near individual target particles with a similar sensitivity. But the bioengineers didn’t stop here. Their logical next step was to design and perform experiments that allowed them to quantify the sensitivity of the biodetector “human white blood cell” to anaphylatoxins.