Immunity is Life (Part II)


Why do I get infections and how does my body fight them?

Living in the world puts your body at risk of infection from disease-causing (pathogenic) micro-organisms like bacteria, viruses and fungi.  If allowed to become widespread these microbes can cause permanent disability and even death.  Just like a medieval town had a wall and moat as a passive barrier to invasion, your body has specialized cells (epithelium) on the surface of the skin and lining the respiratory, gastrointestinal and genitourinary tracts which act as a passive barrier to microbial entry.  If the micro-organisms breach this first line of defense, entering the tissues below, it comes up against the immune system which consists of different cells and proteins.  The first responders to microbial invasion consist of the cells and proteins of your innate (natural) immune system which everyone has at birth.  And just like the sentries of long ago, the innate immune system has four important tasks to perform.

The first task is to identify a microbial invading force that needs to be destroyed.  In other words, are these cells host cells (self), or foreign cells (not self)?  After all, the job of  your  immune system is to kill invading microbes, so it better be sure that what it’s encountering is indeed foreign and in need of  destruction, otherwise it may end up accidentally killing your own cells.  Rather than having eyes and ears to see and hear the enemy your cells interact with other cells, both foreign and domestic, through the surface of their plasma membrane.  To detect a specific set of chemicals on the surface of another cell (like pathogenic microbes) the plasma membrane of your immune cells has specific receptors that can attach to them (like a key in a lock).  The immune cells of your innate system have about a thousand different receptors on their plasma membrane which allows them to attach to the foreign proteins (not present on human cells) on the surface of pathogenic microbes.  This allows them to not only identify them as intruders in need of destruction, but also activates their defense mechanisms.   

The second task is for the immune cells of your innate system to send out messages to bring other defenders to the field of battle.  This is done by these activated immune cells releasing chemicals (cytokines).  The cytokines not only increase the blood flow to the site of infection, allowing various immune cells and proteins to leak out of the blood through the capillaries, but also attracts them to the battlefield as well.  This causes the area around the infection to swell up and become red in a process called inflammation

The third task is to send information about the enemy to the reserves.  This is done by some of the activated first responders snipping off pieces of the microbes they have encountered (and often killed) and placing them on their cell surface.  The reserve cells are then able to come by and check out the information  so that they can be better prepared for what’s awaiting them. 

The fourth task is, by using various weapons, to kill the invaders and prevent the infection from spreading further. 

One important defender of infection is a type of white blood cell called the neutrophils which is part of the innate immune system.  Like other blood cells (red blood cells, platelets), neutrophils are made in the bone marrow and after being outfitted with the weaponry they need move into the blood where they stay on the prowl for microbial invaders.  As the battle on the surface rages and the other immune cells of the innate system become activated, they release cytokines (as noted above in the second task).  These chemicals make the walls of the capillaries leaky which allows the neutrophils to sneak out of the blood and on to the battlefield in the tissues.  By using specific receptors the neutrophils move rapidly toward the increasing concentration of these cytokines to the field of combat.  It’s similar to how a bloodhound moves towards its prey by smelling the increasing concentration of the scent or a shark toward its intended victim by the increasing concentration of blood.  Having come toward the invading microbes, the neutrophils become activated by using receptors on the plasma membrane to attach to specific chemicals patterns on the surface of the intruder (as noted above in the first task).  The activated neutrophil then usually surrounds and engulfs the microbe in a process called phagocytosis.  It then releases various chemicals and enzymes to kill and digest it (as noted above in the fourth task).  After the neutrophils do their job they usually die as it is dead neutrophils that make up most of pus.   

Having enough defenders and their ability to move fast enough and have enough firepower to protect against an invading force determined the survival of a medieval town.  So too, your body must have enough neutrophils that can move fast enough from the blood into the tissues with enough firepower to protect it against life-threatening infection.  Clinical experience teaches us that your blood must have at least 1.5 billion neutrophils per liter to adequately defend from serious infection.  Since neutrophils can’t multiply (like microbes) and generally only live in the blood and tissues for a few hours your bone marrow must produce about one hundred billion every day (or one million per second!).  To maintain this constant production, support cells in the bone marrow release a cytokine called Granulocyte Colony Stimulating Factor (G-CSF) which attaches to specific receptors on immature (stem) cells in the bone marrow and tells them to develop into neutrophils.  Also, in response to infection, some activated immune cells release G-CSF which can often double or triple the number of neutrophils in the blood.  So, although neutrophils can’t multiply on their own, some immune cells stimulate the bone marrow to increase neutrophil production to allow your body to send enough of them to the battlefield so you can live to fight another day. 

However, when it comes to life and being able to defend itself from invading microbes so as not to die from overwhelming infection, real numbers have real consequences.  Clinical experience shows that when the body doesn’t have enough properly working neutrophils to track down and kill enough invading microbes, it dies.  The commonest cause for this is a bone marrow problem called neutropenia which is usually related to cancer and its treatment.   Severe neutropenia is having a neutrophil count less than 500 million per liter of blood and is often associated with a very high risk of septicemia and death.  This is because there just aren’t enough neutrophils around to patrol the body against intruders.  It`s like not having enough defenders to prevent invaders from scaling the walls and taking over a medieval town.  As one would expect, death and destruction are the likely results. 

Three Questions for Mr. Darwin

    1. Where did the information come from to provide the cells of my innate immune system with receptors to detect a thousand different chemical patterns on the surface of invading micro-organisms so they can recognize them to be foreign and in need of destruction? 

    2. Where did the information come to outfit my neutrophils with everything they need to move toward, detect and engulf and kill invading micro-organisms to keep me alive?

    3. How does my body know how many neutrophils it needs to make every second so it can defend me from a life-threatening infection and where did this information come from?

 


Also see Dr. Glicksman's Series on

"Beyond Irreducible Complexity"

"Exercise Your Wonder"


Howard Glicksman M. D. graduated from the University of Toronto in 1978. He practiced primary care medicine for almost 25 yrs in Oakville, Ontario and Spring Hill, Florida. He now practices palliative medicine for a Hospice organization in his community. He has a special interest in how the ethos of our culture has been influenced by modern science’s understanding and promotion of what it means to be a human being.

Comments and questions are welcome.

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