One of the striking things about the COVID-19 pandemic is how differently people respond. Some people contract the virus but never really have symptoms, while others land in the hospital struggling for breath. More than a million people around the world have died from the infection, with about a quarter of those in the US. We can understand this immense variability better if we consider how does the immune system overcome viruses.

Before the immune system can overcome viruses, it has to recognize that pathogens are invading. Human immune systems have two different branches: the innate immune system that kicks in very quickly to respond to anything it perceives as a threat, and the adaptive immune system that responds very precisely to microbes it has met before. How do our bodies know that a pathogen is invading?

Viruses are essentially genetic material–either DNA or RNA–that must invade a host cell and commandeer its genetic material in order to replicate. Some viruses have envelopes surrounding them, while others are “naked.” All viruses can trigger signals called pathogen-associated molecular patterns (PAMPS). These in turn activate the pathogen recognition receptors that put out the alarm to the immune system.

The first responders of the immune system are the cells that make up the innate immune system. Neutrophils, macrophages, monocytes and natural killer cells pick up the signals from the pathogen recognition receptors and react quickly, usually within hours. Part of their reaction is to ramp up inflammation. As a result, an infected cut gets red, swollen and painful. Certain molecules, including cytokines, draw immune cells to the site where they are needed. In the process, they create inflammation.

Such inflammatory chemicals are also responsible for the fever you may experience with a systemic infection. Although many people are quick to try to bring a fever down, that might not be smart. Often a fever can help the body fight off an infection.

Cytokines are an important part of the innate immune response. But when the immune system overreacts, the result can be high fever, respiratory distress and lung damage. Runaway cytokines can also damage blood vessels, a common problem in COVID-19 (The Lancet Respiratory Medicine, April 27, 2020). This is called a cytokine storm.

Our guest is a virologist and immunologist whose special interest is the innate immune system and how it can overcome viruses. Learn about the most promising future approaches against SARS-CoV-2, including ways to make vaccines more effective (Current Opinion in Immunology, Oct. 7, 2020).

Michael Gale, Jr., PhD, is a professor of Immunology at the University of Washington School of Medicine. Dr. Gale is a formally trained immunologist and virologist whose research is focused on understanding the molecular mechanisms of innate immune response and immune programming against infection by RNA viruses, including emerging SARS-CoV-2, emerging flaviviruses, HIV, and influenza viruses. 

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