The immune system regulates disease response throughout our bodies. Interestingly, two separate responses act as barriers to prevent the spread of infections. When first introduced to a disease, the innate immune system quickly identifies infections as foreign. Many different innate immune cells circulate throughout the body surveying tissues for anything that they do not identify as ‘self’. This regulatory system reacts to disease more generally and in a non-specific manner. As a result, innate immunity can eliminate many infections but cannot completely remove more aggressive viruses. However, the innate immune system triggers a second immune response, which specifically targets infected cells.
The adaptive immune response works in concert with the innate immune system to deliver complete and effective protection against disease. Two cell types that make up the adaptive immune response include T and B cells. Specifically, T cells are responsible for recognizing infection and eliminating them while B cell generates antibodies to target and neutralize disease. Unfortunately, immune cell dysregulation can have deleterious effects on the body and cause have long-term consequences.
A recent article in Immunity, by Dr. Purvesh Kharti and others, demonstrated that groups with dysregulated immune systems predict outcomes from infection. Researchers found that four groups had immune dysregulation that generated severely dangerous outcomes from disease. Immune dysregulation risk was increased in groups that were male, over 65 years old (yo), smokers, and/or obese. As a result, each group was found to have an increased risk of severe outcome due to infection. Kharti is Associate Professor of Medicine at the Institute for Immunity, Transplantation and Infection at Stanford University. His work focuses on developing new ways to diagnose and treat tumors that are aggressive and tend to elude current therapeutic treatments.
Kharti and his group have identified a gene signature of immune dysfunction to predict disease outcome. Gene signature refers to the genes in a cell that are up- or downregulated. These genes are encoded to make proteins needed for the cell to function and respond to stimuli. The expression of specific genes determines how a cell will act. By developing a signature or an applied gene expression pattern, researchers can predict how a patient will respond to infection. Unfortunately, the gene signature predicts poor disease outcome in patients from the previously mentioned groups – male, above 65 yo, smoker, and obese. However, researchers say that this signature can be modified by living a healthy lifestyle.
Currently, in the field of immunology and medicine, scientists are unsure what a ‘healthy’ immune system looks like. This work tries to define a healthy gene signature to provide a baseline for healthy immunity. Once the team identified a ‘healthy’ and ‘unhealthy’ gene signature, they were able to apply it to treatment response in bacterial sepsis, burns, and asthma. This discovery could have major implications in personalized medicine and inform physicians on which treatments are optimal for each patient. Kharti and his team are currently applying their signatures to patients with chronic illness in the clinic. They are also investigating what happens when patients that have a modifiable behavior, like smoking, choose to live a healthier lifestyle (no smoking). Such changes can modify a gene signature and consequently change predicted treatment outcomes. Overall, a reliable immune signature could be regularly used in the clinic and direct patients on ways to improve their health.