Author: Will Humble

Part I – Antibodies, Leukocytes & T Cells

Over the last several months we’ve learned a lot about the nature of the immune response when someone is sick with and then recovers from a SARS CoV2 infection. At first, it was unclear whether and for how long immunity might last after recovery. Most of the public and media discussion has been about the lasting effect of neutralizing antibodies following recovery from COVID-19….  but the immune system is so much more than just an antibody response.

This week I’m doing my best to explain the basics of the immune system, how it works and it’s different components.

What Is the Immune System?

The immune system is the body’s defense against infections from pathogens like bacteria and viruses. It consists of a combination of different kinds of cells that attack pathogens to keep us healthy. Our immune system can detect different kinds of disease agents and it’s really good at telling the difference between harmful and harmless or even beneficial organisms (e.g. viruses, bacteria, and parasites).  It can tell the difference between the body’s own healthy cells or tissues, and ‘foreign’ cells.

When the immune system recognizes a pathogen (let’s take the SARS CoV2 virus as an example) it activates the immune system to protect the host. That immune response starts with intelligence gathering.

Intelligence Gathering

The immune system’s “intelligence gatherers” are called B lymphocytes.  You might also know them as Bursa cells. These cells go around the body all the time and look for foreign objects that could be harmful. They’re looking for “antigens” or proteins that look strange and potentially harmful.

For example, the SARS CoV2 virus that causes COVID-19 has a has a protein coat that is unique to that virus. The antigens, or protein coat spikes are those sharp looking things that are often depicted in the media when they show the virus. The immune system’s B cells brush up against the virus and gather intelligence- and when they see the SARS CoV2 virus, they immediately think uh-oh.  This is not good. Let’s make some antibodies to fight this antigen.

Emergency Response

Those antibodies are the “first responders” of the immune system. You can think of antibodies as firefighters that rush in to fight the threat that the invading virus may be posing. The B lymphocytes (B Cells) make the antibodies (also called immunoglobulins).  They are proteins that lock onto the specific antigen that’s the threat. 

You can think of it like a lock and key. The key needs to fit the lock to open the door. It’s like that, the antibody needs to fit the antigen to work too. When the key and the lock fit- the harmful virus becomes neutralized. Not dead, but neutralized.

There are several different kinds of antibodies. Two of the most important at IgM and IgG. Both are antibodies, but they have slightly different purposes. The IgM antibodies produced by the B cells form first, within the first couple days after infection. They do an OK job, but they aren’t super effective- but they can be made really fast. IgG antibodies take longer to make but do a better job once they get there.

Antibodies lock on to the threat and neutralize it, but they can’t kill the virus without help. The antibodies put handcuffs on the virus so that it’s held in abeyance until assistance arrives.  The first help to arrive is a group of proteins called “complement”.

The complement arrives and sees that an antibody has locked on to the SARS virus.  Complement triggers a chemical reaction that damages or kills the viruses, infected cells and other close by cells that are healthy. The complement is a pretty blunt immune system instrument because it kills both the virus, infected cells and other cells that aren’t infected. 

But more help is on the way.  They’re called “phagocytes”.

Calling in the Cavalry

Phagocytes are immune system cells that “eat” harmful foreign particles, bacteria, as well as dead or dying cells. These cells come to the rescue when they see that antibodies have been neutralizing harmful pathogens and causing a complement response. These “professional” phagocytes include a host of different white blood cells called neutrophils, monocytes, macrophages and dendritic cells.

These cells act to kill the invading organism, but it comes at a cost, because healthy host bystander cells are destroyed as the phagocytes react to the threat.  The macrophages and neutrophils for example cause an inflammatory response that damages healthy host tissue. They destroy pathogens by engulfing them and subjecting them to toxic chemicals. 

Sometimes those toxic chemicals are released into the environment causing the damage to healthy host cells. This process helps the body get rid of the harmful invaders but also causes inflammation to normal healthy cells that are bystanders.

Bringing in the Specialists

The immune system specialists are the T Cells.  They provide an important role in controlling and shaping the overall long-term immune response.  They use signaling proteins called cytokines to recruit to mount an immune response. Other kinds of T cells are called “helper cells” which indirectly kill foreign cells by attracting phagocytes.

The T cells learn to specifically target the harmful invaders and can attack those invading virus and bacteria in a targeted way that causes less collateral damage to the surrounding tissue. They can also recognize, target, and destroy things like cancer cells. 

People spend their whole career studying T cells and their function in the immune system- so their work is complex and important.

Part II Tomorrow: Is there Lasting Immunity Post Infection?

Bars have now opened across almost all of Arizona. There are just a few counties that haven’t yet met the moderate spread metrics- and over 90% of Arizonans now live in counties where bars are open. In order to open, bars are supposed to go to the ADHS website and attest that they will follow mitigation measures.

Following mitigation measures is critical in these businesses. As we saw between May 15 and June 26 bars and nightclubs create super-spreading environments without mitigation.

Over the last couple of weeks there has been some strong administrative advocacy urging the state to develop a meaningful compliance program to ensure that bars and nightclubs follow the required mitigation measures upon opening. ADHS had already been requiring bars and nightclubs to sign attestations that they’ll follow mitigation measures, but until late last week there wasn’t an organized active compliance system.

The advocacy worked and late last week the department announced that they would be sponsoring a COVID-19 Compliance Hotline at 1-844-410-2157.  They committed to investigating complaints by referring them to the county health departments or in some cases investigating the complaints themselves.

Editorial Note: Let’s hope that the plan is well organized and works. If the compliance program isn’t effective, we can expect broad non-compliance with mitigation as we say earlier this summer, creating an increase in cases. If that happens, students in the K-12 system will suffer if that happens because counties would no longer meet in person instruction benchmarks in short order. That lost opportunity would be directly attributable the lack of an effective compliance system for bars and nightclubs.

Last week the FDA issued an emergency use authorization to Yale School of Public Health for its SalivaDirect COVID-19 diagnostic test, which uses a new method of processing saliva samples when testing for COVID-19 infection. SalivaDirect does not require any special type of swab or collection device; a saliva sample can be collected in any sterile container.

As the nation continues to grapple with the ongoing COVID-19 pandemic, the Network has joined with public health law partners to produce a report that includes critical analyses and recommendations from 50 national experts convened to assess the U.S. policy response to the crisis to date.

This new report offers policy recommendations on 35 wide-ranging topics, including pandemic preparedness, access to health care, voter health and safety, protections for essential workers, food insecurity and immigration policy. Designed to advise leaders at the federal, state and local level, the report presents a timely examination of policy challenges and opportunities in light of the pandemic.

Read the full report here. 

Back on August 3, the CDC issued new guidance regarding people who are infected with the coronavirus. It flew under the radar until the New Your Times wrote a story about that change.  Following the NYT article, other media outlets improperly interpreted the new CDC guidance and wrote stories suggesting that immunity wanes after 3 months. That is not what the CDC guidance said.

What the CDC actually said was that “People who have tested positive for COVID-19 do not need to quarantine or get tested again for up to three months as long as they do not develop symptoms again. People who develop symptoms again within three months of their first bout of Covid-19 may need to be tested again if there is no other cause identified for their symptoms.”

Last Friday the CDC issued a clarifying statement saying, “Contrary to media reporting today…  the latest data simply suggests that retesting someone in the 3 months following initial infection is not necessary unless that person is exhibiting the symptoms of COVID-19 and the symptoms cannot be associated with another illness.”

Some scientists have speculated that immunity from the virus might only last 3 months based on a study published in Nature back in June that showed many patients began to show decreasing levels of immunity 2–3 months after infection and that antibodies may not last very long among asymptomatic mildly ill persons.

But remember, antibodies are just one part of the immune system and it’s normal for antibodies to decrease once an infection recedes.  It also doesn’t mean that waning antibody titers mean waning immunity.  The memory B cells that first produced those antibodies are still around and stand ready to make more antibodies on demand. There is also good evidence that people infected with the SARS virus also generate a robust T-cell response- providing a longer lasting type of immunity.

Next week I’ll do a have a piece on the immune system and how it works with an eye toward the pandemic.