How Rochester's Immunologists Decode Your Body's Defense System
Every moment of every day, an intricate defense network works tirelessly to protect your body from countless potential threats. This system—our immune system—must perform an extraordinary balancing act: attacking harmful invaders like viruses and bacteria while sparing our own healthy tissues. When this balance fails, the consequences can be devastating, leading to autoimmune diseases, cancer, or uncontrolled infections.
The immune system protects against pathogens while maintaining tolerance to self-tissues.
Critical balance between attacking invaders and avoiding autoimmunity.
At the University of Rochester Medical Center, scientists are unraveling the mysteries of this complex biological defense network. Their work spans from fundamental discoveries about how immune cells function to developing innovative treatments for some of medicine's most challenging conditions. In this article, we'll explore the fascinating world of immunology through the groundbreaking research happening at Rochester, where scientists are translating laboratory discoveries into real-world medical solutions.
At the core of immunology lies a critical concept: immune tolerance. Imagine your immune system as a highly trained security force that must accurately distinguish friends from foes. It needs to aggressively attack dangerous pathogens while completely ignoring your own healthy cells. This ability to recognize "self" and avoid attacking it is what scientists call immune tolerance.
For decades, immunologists believed that this tolerance was established primarily during immune cell development in the thymus (central tolerance). However, groundbreaking work that would later win the 2025 Nobel Prize in Physiology or Medicine revealed a more complex story. Researchers Shimon Sakaguchi, Mary E. Brunkow, and Fred Ramsdell discovered that tolerance is actively maintained throughout the body by specialized cells called regulatory T cells (T-regs) 2 5 .
Regulatory T cells function as the security guards of your immune system, constantly monitoring other immune cells to prevent them from attacking your own tissues. The Nobel Committee recognized the Rochester-relevant work of Sakaguchi, who in 1995 first identified these specialized cells, and Brunkow and Ramsdell, who in 2001 discovered the Foxp3 gene that controls their development 5 9 .
"When these security guards malfunction, the immune system can turn against the very body it's meant to protect."
Autoimmune diseases like rheumatoid arthritis, type 1 diabetes, and multiple sclerosis occur when this tolerance breaks down. Conversely, when T-regs are overactive, they can suppress immune responses too effectively, potentially allowing cancer cells to evade detection and destruction.
In 1995, Shimon Sakaguchi and his team conducted a series of elegant experiments that would fundamentally change our understanding of immune regulation 9 . Their work addressed a crucial question: if the thymus already eliminates self-reactive immune cells, why do autoimmune diseases still occur?
The researchers hypothesized that there might be additional mechanisms outside the thymus that maintain immune tolerance—what they called "peripheral tolerance." To test this, they designed experiments using mouse models to identify what cell populations were essential for preventing autoimmunity.
Researchers first analyzed different subpopulations of T cells in normal mice, paying particular attention to surface markers that might distinguish functional subsets.
They selectively removed CD25-expressing cells from normal mice and transferred the remaining cells to mice that lacked their own immune systems.
The recipient mice were then monitored for development of autoimmune symptoms, including tissue damage in various organs.
To confirm their findings, researchers then transferred CD25+ cells back into the affected mice to see if this would prevent or ameliorate the autoimmune symptoms.
The suppressive function of these CD25+ cells was further tested in laboratory cultures to understand how they control other immune cells.
Mice that received T cells depleted of CD25+ cells rapidly developed multi-organ autoimmune disease 9 .
Immune tolerance isn't just established during cell development—it's actively maintained throughout the body by specialized cells.
The findings were striking. Mice that received T cells depleted of CD25+ cells rapidly developed multi-organ autoimmune disease 9 . Their immune systems were attacking their own tissues, demonstrating that the removed cells were essential for maintaining tolerance.
When the researchers transferred the CD25+ cells back into these mice, the autoimmunity was prevented. Further tests showed these cells could suppress the activation and proliferation of other T cells in laboratory experiments. Sakaguchi had discovered what we now call regulatory T cells (T-regs)—the dedicated security guards of our immune system.
| Experimental Group | Autoimmune Symptoms | Conclusion |
|---|---|---|
| Normal mice | No | Healthy immune balance |
| Mice receiving CD25-depleted cells | Yes (multi-organ) | CD25+ cells prevent autoimmunity |
| Mice with restored CD25+ cells | No | T-regs can suppress autoimmunity |
This discovery was revolutionary because it revealed that immune tolerance isn't just established during cell development—it's actively maintained throughout the body by specialized cells. The implications were enormous, suggesting new approaches for treating autoimmune diseases, improving organ transplants, and enhancing cancer immunotherapy.
Modern immunology research relies on sophisticated tools and techniques that allow scientists to probe the intricate workings of the immune system. At the University of Rochester, researchers utilize a diverse array of these technologies across their studies of autoimmune disease, cancer immunology, and host-pathogen interactions 3 .
| Tool/Reagent | Primary Function | Application Examples |
|---|---|---|
| Flow cytometry | Identifies and sorts cells by surface markers | Identifying T cell subtypes (CD4, CD8, T-regs) |
| Cytokine assays | Measures signaling proteins | Quantifying inflammation in autoimmune diseases |
| Gene editing (CRISPR) | Modifies specific genes | Studying Foxp3 function in T-reg development |
| Animal disease models | Mimics human conditions | Testing new therapies for rheumatoid arthritis, MS |
| 3D in vitro models | Recreates human tissue environments | Studying immune cell trafficking in tumors |
These tools have become essential in Rochester's research programs. For example, the Program for Advanced Immune Bioimaging allows scientists to visualize immune responses in real time, providing unprecedented insights into how immune cells locate and interact with their targets 3 .
Meanwhile, studies on SARS-CoV-2 immune responses and HIV pathogenesis utilize cytokine profiling and advanced cell sorting techniques to understand why some immune responses succeed while others fail 3 .
The university's focus on translational research—bridging basic discoveries to clinical applications—means these tools are constantly being refined and applied to address pressing medical challenges. From developing new anti-infective drugs to designing innovative cancer immunotherapies, Rochester scientists are equipped with state-of-the-art methodologies to advance human health.
The University of Rochester has established itself as a hub for immunological research, with programs that span from fundamental molecular studies to clinical applications. The Immunology, Microbiology, and Virology (IMV) PhD Program provides training across these disciplines, preparing the next generation of scientists to tackle complex immunological challenges 1 6 .
Several laboratories at Rochester focus on understanding and treating autoimmune conditions. The Anolik Lab investigates B cells and their role in immune diseases, while other research groups study the regulation of immune responses and mechanisms that ensure appropriate termination of immunity after pathogen clearance 3 .
Rochester researchers are also exploring how to harness the immune system to fight cancer. The Robert Lab studies the evolution of immune surveillance and tumor immunity, seeking to understand why immune systems sometimes fail to eliminate cancer cells and how to enhance anti-tumor responses 3 .
Understanding immune responses to pathogens is another major research focus at Rochester. Laboratories like the Topham Lab study respiratory virus immunity, while the Singh Lab focuses on immune-pathogenesis of viral infections including HIV and SARS-CoV-2 3 .
| Research Area | Key Questions | Example Labs |
|---|---|---|
| Autoimmune Disease | How is immune tolerance maintained? What causes breakdown? | Anolik Lab, Yarovinsky Lab |
| Cancer Immunology | How do tumors evade immune detection? Can we enhance anti-tumor immunity? | Robert Lab, Minsoo Kim Lab |
| Infectious Disease | What constitutes effective immunity against pathogens? How do pathogens evade immunity? | Topham Lab, Singh Lab |
| Immunoregulation | How are immune responses controlled and terminated? | Sant Lab, Schwarz Lab |
The journey to understand our immune system—from the initial discovery of regulatory T cells to today's sophisticated research at institutions like the University of Rochester—represents one of the most exciting frontiers in modern science. Each discovery reveals new layers of complexity but also new opportunities for therapeutic intervention.
"The mentorship and the exceptional research experiences I had in the IMV program prepared me for my academic career. The program really does a great job of addressing many of the skills you will need to be successful once you complete your training."
— Brendaliz Santiago-Narvaez, PhD, University of Rochester alumna
The future of immunology lies in leveraging our growing understanding of immune regulation to develop smarter, more targeted therapies. Whether it's engineering regulatory T cells to treat autoimmune conditions, designing vaccines that provide broader protection against evolving pathogens, or developing combination therapies that unleash immune responses against cancer while preventing autoimmunity, Rochester scientists are at the forefront of these advances.
As we continue to unravel the mysteries of the immune system, each discovery brings us closer to more effective treatments for some of medicine's most challenging diseases. The silent guardians within our bodies may soon have new reinforcements, thanks to the dedicated researchers working to understand and harness their power.