Your Own Private Security Force

It is a rough world out there beyond the confines of your body. Viruses, bacteria, and parasites lurk just over the border, ready at any time to storm the gates and ravage your health.  But against these potential invaders, your healthy body possesses a tremendous and sophisticated army to defend against illness.

Comprised of various kinds of white blood cells and other structures, the immune system keeps constant vigil to identify and destroy any threat.  Like any effective military, this cellular force must be able to deal rapidly and decisively with its foes, while maintaining peaceful relations with citizens at home. Each soldier must learn to recognize and tolerate cells from within the body to minimize friendly fire.  And the troops engage in public works by repairing damaged tissues.

Like a wall encircling a castle, our skin serves as the front line of defense against the hordes of germs.  But there are gates in every fortress.  Invaders can enter through cuts in the skin or through natural openings like our mouths, noses, eyes, genitourinary system, and gastrointestinal tract.

These points of entry into our bodies require special attention from the immune system.  Its members sort through and deal with microbes in those locations the way that border guards assess the threat on a wild frontier.  Not every duty involves fighting.  Some of it amounts to police, detective, and spy work.  Each cell has a part to play.

The Corps of Corpuscles

The foot soldiers of the body are the phagocytic cells – neutrophils, macrophages, and dendritic cells.  Every military needs boots on the ground and a healthy supply of grunts.  These infantry cells gobble up germs and either kill them by digestion or just chew on them for a while until presenting pieces of the microorganisms for analysis to cells further up the chain of command.

Natural killer cells are the military police.  They recognize our own cells that have become infected with viruses (or turned cancerous) and execute the traitors before they spread the infection.  Then there are proteins, known as the complement system, which float in the blood and destroy invaders upon contact, the way mines sink enemy ships.

B lymphocytes, like an air force, fire antibodies into the blood stream.  These complex and highly precise structures act as bombs that can neutralize germs throughout the body without the need for hand to hand combat.  Furthermore, antibodies are like smart bombs, precisely designed to target only specific germs.

But it takes time to design and mass-produce smart bombs.  Most importantly it requires intimate knowledge of the target, so the weapon can be created specifically to destroy only a particular pathogen and do no other damage.  For this reason, antibody responses to new infections take time to mount.  Typically, they appear only a week or two after an infection, as an adaptive response of the immune system.  After an infection (or a vaccination), antibody levels can persist for months, if not a lifetime, like a mine field laid to prevent a renewed attack.  This provides long term immunity, so that you don’t get sick a second time with the same bug.

The top brass in the immune system are lymphocytes, known as T cells.  In addition to fighting, they also direct and incite other cells to do so.  Some types of T cells join directly in the battle against infections.  Others have a different, but critical, job.  They remember.  What is so important about that?

A Seasoned Soldier

Imagine that you are exposed unknowingly to, let’s say, the chicken pox virus.  In fact, suppose that following your exposure, there are now many of the viruses (also called varicella zoster virus) in your lungs.  They are beginning to invade and multiply.  Unless something changes, you will soon have a cough and fever, followed by a week of itchy red bumps all over your body.  Your coworkers will treat you like an outcast. If you are an adult, you could even die of pneumonia.

But something is about to change that narrative.  A dendritic cell, stationed like a guard on duty in your lung, swallows something tiny that it does not recognize as belonging to your body.  It is one of the viruses.  The dendritic cell wriggles its way through a lymphatic channel, like a private navigating the trenches on the front lines, and slithers into a lymph node, the local command center.  Finally, it touches a familiar receptor on a T cell in what amounts to a molecular salute.  The dendritic cell presents some of the digested pieces of the chicken pox virus to the T lymphocyte, like a guard showing a passport to a superior officer.

This T cell does not dither.  It gives the order: “Attack!”

This command rouses the full force of all branches of the immune system to join the battle at once.  B cells, already armed for this moment, churn out antibodies that rain down death on the virus.  Neutrophils hem in the pathogen, peppering it with toxic granules like hand grenades.  Macrophages feast on the foreigners.  Other dendritic cells stretch out their bayonet-like projections to ensnare the invaders.

The offensive is intense, but brief.  Fired up and guided by chemical orders from the T cell, the soldiers of the immune system quickly dispatch all the viruses.

Viral Veteran

But how did the T cell “know” how to respond to the threat?  These cells are exposed to countless foreign substances every day, and they don’t sound the alarm.  And how were the B cells, the bombers of the cellular corps, already loaded with antibodies specifically configured to target the chicken pox virus?  How could these microscopic marines already be so familiar with this foe and vanquish it so quickly?

The answer is immunity.  You are “immune” to chicken pox, because you either had the infection in the past (if you are currently over about 30 years old) or you were vaccinated against it.  And ever since that earlier exposure to the real or the simulated virus (which is basically what an immunization is), this T cell, like some crusty old military historian, has remembered its foe and has kept constant vigil against a repeat invasion.

Throughout its extraordinarily long life (by cell standards), this “memory T cell” has ruminated, strategized, and waited for this moment.  Be thankful for this lengthy lifespan and long memory.  Thanks to them you won’t get so much as a single pock!

Too Late?

Let’s return to a specific case of COVID-19.  Do you remember Peggy, the unfortunate 68 year old woman with pneumonia and organ failure?  We left her barely clinging to life on a ventilator in an ICU.

In her case the same type of cellular interaction I have been describing occurred: one of her dendritic cells swallowed a SARS-CoV-2 virus and presented its foreign insignia to a ranking T cell.  But the T lymphocyte failed to recognize the threat in time.  Why the difference?  That is because SARS-CoV-2 is a new (novel) virus.  Peggy’s immune system (and most of ours, for that matter) had never encountered this pathogen, either directly on the battlefield (through an actual infection) or in the simulated “war games” provided by a vaccine.

Peggy had no immunity to the novel coronavirus.  By the time the central command in her immune system realized that an invasion was taking place, it was too late.  Multiplying, moving, and hiding within infected cells, the coronavirus wreaked havoc, before her body could mount an effective counterattack.

(It is worth mentioning here the strange, but encouraging possibility that some of us may actually be immune to COVID-19 even though we have never been exposed to the virus and we have no detectable antibodies to it.  How could that be?  (There is an upcoming post  “HERD IMMUNITY” that will address this further.)

Despite the lag and the severe infection, Peggy’s immune system eventually did come up to speed and engage its bitter enemy.  You might even say that her immune system gained the upper hand, considering that by day sixteen of her illness, she has had two consecutive negative COVID tests, evidence that she may have eliminated the virus from her system.  Yet she remains critically ill and near death.  Why is she still sick?  If there are no viruses, what is causing the ongoing damage to her organs?

This will be the topic of the next post – the immune overreaction to COVID-19 infection that leads to severe disease and the possible treatments based on that.  But first I want to point out an irony about the pandemic.

The Microscopic Mirrors the Global

It is fascinating – and ironic – to me that the same dynamic occurring at the microscopic level between cells of infected persons also occurred in early 2020 on a worldwide scale at the highest levels of global health.

Just as T cells, the higher authorities in the immune system, failed to recognize the threat presented by a new virus in previously unexposed individuals, so in the same way many public health authorities and leaders around the globe failed to recognize the threat of a pandemic posed by the novel coronavirus.  In fairness to them – and to Peggy’s T cells – this was a new threat.

It is helpful for me to remember that.  Though we may cast blame all about, we are novices in this fight against the global pandemic of COVID-19.  We have made many mistakes in this conflict, but rookies always do.

Educators, merchants, restauranteurs, politicians, researchers, doctors, public health officials – we are still green and on foreign soil, as we battle together.  Most of us are doing our best.  Almost all of us exhibit inconsistencies as we try to move forward.  The pandemic is hard for everyone.  Maybe we can be more gracious to one another if we consider that.  Give your T cells – and your fellow man – the benefit of the doubt.