A well-respected researcher who is now a chief of an immunology laboratory of the National Institutes of Health (NIH) has rocked the boat in the past few years for the experts in the understanding of the autoimmune system.
NIH’s Polly Matzinger has developed the "danger model," suggesting that the immune system is more concerned with damage detected on the basis of a biological cell’s death than with the introduction of foreign invaders, such as viruses. If Matzinger is correct, then decades of scientific and medical diagnostic thinking could be in jeopardy.
As immunologists consider the relatively new concept, a new NIH grant, awarded to Amy Bell, an electrical and computer engineer (ECE), and Karen Duca, a research assistant professor at the Virginia Bioinformatics Institute (VBI), both of Virginia Tech, could answer some of the questions about the human body’s responses to viruses. Viruses cause a number of diseases, from the common cold, to herpes, to AIDS. Even some types of cancer have been linked to viruses.
Prior to Matzinger’s model, the common assumption was that the body’s cells recognize substances or germs that do not come from within the body. The recognition triggers the immune system’s attempt to eliminate the invader. But what the immune system actually does, according to Matzinger, is discriminate between things that are dangerous and things that are not. And it does this by defining anything that does damage as dangerous. Through this selectivity process, the immune system does not respond to things that don't do damage.
Examples she uses to support her thesis that the body recognizes some invading substances are not dangerous include the development of a fetus during a woman’s pregnancy and the production of milk by lactating women.
So the question remains: do we really know what a body’s host cell does when a virus infects it?
Bell and Duca’s collaboration is an attempt to profile the host-virus system using the electrical engineering concepts of signal and image processing. As Duca, a biophysicist, introduces viruses into cells in a laboratory dish, she infects only the cell’s center. Then, she and Bell, who is also a VBI faculty fellow, study the response as the virus moves outward. Their method differs from conventional laboratory studies of viruses that generally involve infecting the entire dish at once.
As the virus moves out from the center in its attempt to infect other healthy cells, Duca identifies and stains relevant markers from the virus and the host. Under ultraviolet lighting, the chemical stains become fluorescent, allowing Bell and Duca to capture images of the laboratory dish at regular time intervals as the infection progresses. The images then provide Bell and Duca with information about innate immune responses to viruses.
Using the NIH support of almost $400,000, Bell plans to next remove the noise from these low-resolution images, creating what she calls a clean immuno-fluorescent intensity signal. The noise she refers to is not audible to the human ear. From an electrical engineering standpoint, noise in this example includes the spurious artifacts that appear in the image due to the microscope’s uneven source illumination. Noise can also result from the spectral overlap of the fluorescent markers that Duca uses.
Also, since the microscope cannot capture the entire laboratory dish at once, multiple sub-images must be taken quickly, then reassembled in the proper matrix. The “montage” artifact arises from the microscope’s uneven illumination, which is brighter in the center and dissipates nearer the edges of the dish for each sub-image.