The immune system continues to fight infections acquired at birth even into adulthood, though its effectiveness remains limited
Image Credit: Scientific Frontline
Scientific Frontline: Extended "At a Glance" Summary: Immune Response to Perinatal Hepatitis B Infections
The Core Concept: Contrary to the long-held belief that the immune system fully tolerates chronic viral infections acquired at birth, recent research demonstrates that the body's defenses actively continue to fight these lifelong infections into adulthood, albeit with limited efficiency.
Key Distinction/Mechanism: Historically, perinatal infections like Hepatitis B (HBV) were thought to induce complete immune tolerance, allowing the virus to persist unchallenged. The newly discovered mechanism reveals that the immune system does produce antibodies supported by T helper cells. However, because the initial infection occurs during a sensitive developmental phase of the immune system, these T helper cells are less frequent and less diverse than those generated during adult-acquired infections, causing the immune response to operate in a permanently restricted state.
Major Frameworks/Components:
- Perinatal Infection Models: Utilization of specialized mouse models that replicate key aspects of birth-acquired infections to observe longitudinal immune responses.
- T Follicular Helper Cell Activity: Identification of specialized immune cells that actively support antibody production, but remain quantitatively and qualitatively restricted.
- Partial Immune Tolerance: The phenomenon where early-life viral exposure limits the formation of specific T cells, allowing the pathogen to persist indefinitely without completely neutralizing the body's defenses.
- Therapeutic Enhancement: Experimental administration of supplemental T helper cells successfully boosted the host's antibody response, proving the existing immune action can be pharmacologically or biologically amplified.
Branch of Science: Immunology, Virology, and Biomedicine.
Future Application: This research provides a biological foundation for novel immunotherapies aimed at curing chronic viral infections. By therapeutically boosting existing, partially effective defense mechanisms—such as increasing T helper cell availability—scientists can develop targeted treatments rather than attempting to induce an entirely new immune response from scratch.
Why It Matters: More than 250 million people globally live with chronic Hepatitis B, the vast majority of whom acquired the virus at birth. Shifting the fundamental understanding of how the adult immune system interacts with early-life infections opens viable new pathways for curing conditions that were previously considered incurable.
Millions of people worldwide carry viral infections they acquired at birth, often for life. For a long time, it was assumed that the immune system hardly fights these pathogens. Researchers from the University of Basel show now that the body’s defenses do indeed act against the virus. This could be a useful starting point for future therapies.
Modern medicine can often prevent viruses from being passed from mother to child during birth, for example in the case of the hepatitis B virus (HBV). However, once the infection is established, it still cannot be cured. More than 250 million people worldwide live with a chronic HBV infection, almost all of them since birth.
Until now, it was assumed that the immune system tolerates such infections and hardly defends itself against them. A new study by researchers at the Department of Biomedicine at the University of Basel provides evidence that the immune system fights these infections more effectively than previously thought.
“Our study changes the way we think about chronic infections that begin early in life,” says Dr. Katrin Martin, co-first author of the study published in Immunity. “We found that the immune system continues to fight the virus in adulthood with partial success, although it is, in a sense, operating with the brakes on.”
How the body responds to the virus
Using a mouse model that replicates key aspects of an infection acquired at birth, the research team examined the immune response over an extended period. The results showed that the body gradually produces antibodies that help reduce the amount of the virus. This response is supported by specialized immune cells known as T helper cells, which enable other immune cells to produce more effective antibodies.
These T helper cells are indeed active and effective in adulthood. “However, they are less frequent and less diverse than those seen in infections encountered later in life,” explains co-first author Dr. Peter Reuther. As a result, the immune response remains limited and is unable to completely eliminate the virus.
Strengthening the immune response in a targeted way
In the next step, the researchers investigated whether this limited immune response could be enhanced. In their experiments, they were able to improve the antibody response by administering additional T helper cells to the mice. This suggests that the reduced availability of T helper cells is an important limitation of the immune response to infections acquired early in life.
The researchers suspect that this is because the viral infection occurs during a sensitive phase of the immune system’s development. As a result, the formation of specific T cells remains limited, and the organism develops partial tolerance to the virus, allowing the latter to persist in the body indefinitely.
“The fact that the immune response can be enhanced by adding T helper cells is promising for the development of new therapeutic approaches,” says study leader Professor Daniel Pinschewer. “Building on existing and partly effective defense mechanisms is more promising than trying to induce an immune response that is completely lacking.”
Published in journal: Immunity
Authors: Katrin Martin, Peter Reuther, Florian Geier, Anna-Friederike Marx, Tiago Abreu-Mota, Jonas Fixemer, Anna Lena Kastner, Weldy V. Bonilla, Karen Tintignac, Karsten Stauffer, Min Lu, Dominik Schuler, Ingrid Wagner, Doron Merkler, and Daniel D. Pinschewer
Source/Credit: University of Basel | Martina Konantz
Reference Number: imgy042826_01
