26 August 2025
Virtual Reality StudyUncanny virtual humans trigger immune response

Photo: Microsoft Rocketbox Avatar Library / University of Hamburg
The uncanny valley effect describes how robots or digital characters modeled on humans, so-called virtual agents (VA), can trigger negative emotional responses in test subjects—particularly, if the artificial images are perceived as eery or odd. Inconsistent proportions or an unnatural body postures may elicit such a response. The University of Hamburg research team has now investigated whether the brain interprets feature deviation as a symptom of illness and a possible risk of infection.
The scientists, led by human biologist Dr. Esther Diekhof and informatics expert Prof. Dr. Frank Steinicke, confronted test subjects with humanoid VA in a virtual environment and then measured the concentration of secretory immunoglobulin A (sIgA). This antibody can be detected in human saliva and is an indicator of a person’s immune activity. The researchers were able to show that the immune system reacts to deviant VAs by increasing slgA levels.
They compared the sIgA immune response to uncanny VAs with changes in slgA levels measured after contact with optimized, significantly more human VAs and simple cartoon VAs. In these test scenarios, no increase in the immune response could be detected in the saliva.
“This shows that humans perceive deviating external characteristics—even if artificial images only—as a potential health threat which supports the so-called pathogen avoidance theory as a possible explanation of the uncanny valley effect,” says Dr. Esther Diekhof, head of the Neuroendocrinology Group in the Department of Biology. Abnormal features seem to be mistaken for signs of communicable diseases, so the immune system presumably prepares itself to prevent infection. This could be an important reason for rejecting and avoiding eery VAs.
Supplementary questionnaires, however, in which the 66 test subjects reflected on both the appearance of the virtual contacts and their own feelings, showed no major differences in the assessment of the 3 VA groups. According to the research team, this indicates that the immune response happens unconsciously. “Relatively automatic, the brain deduces a potential danger from the visual information and activates the immune system as a precaution,” says Diekhof. This principle applies: making a false assessment is better than missing a disease threat—better safe than sorry.
Similar immune reactions were detected in test subjects exposed to a sneezing, clearly symptomatic virtual contact person. The current study focused entirely on slight physical deviations, particularly around the mouth and eyes.
“We aimed for the test subjects to approach the virtual agents in a most realistic virtual environment and make direct eye contact for a longer period of time. Tasked with making their odd-looking virtual contact person smile they could not avoid them or keep their distance to prevent infection,” says Prof. Dr. Frank Steinicke, head of the Human-Computer Interaction working group at the Department of Informatics.
The results showed that there is a significant correlation between the increase in slgA levels and the perceived immersion. “A virtual reality that is experienced as credible seems to reinforce the perceived health threat posed by weird-looking virtual agents,” says Steinicke.
Original publication:
Diekhof, Esther; Deinert, Donna; Foerster, Monika; Kastner, Svenja; Steinicke, Frank: The uncanny valley effect and immune activation in virtual reality Sci Rep 15, 30473 (2025). https://doi.org/10.1038/s41598-025-15579-4
Podcast
An AI-generated podcast based on a preprint version of the paper is available on Spotify and gives an auditory impression of the research.
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