June 1, 2004

Sports are Simply a Reflection of Life (Without a good defense, you're dead; literally!)

By Dr. Howard Glicksman

Consider most of the common sports that we see played; football, baseball, hockey, soccer and basketball.  Football has its front four, linebackers and defensive backs; baseball has the infield and the outfield; and hockey, soccer and basketball require most of the players to play a certain amount of defense to have a chance of winning the game.

Well, winning the battle for life not only requires us to have the offensive ability to track down, procure and eat and drink what we need to survive, it also requires us to have the ability to defend ourselves against foreign invasion.  I’m talking here on the microscopic level, a sort of 9/11 defensive strategy, a Homeland Security for the body!  

The year is 1882, and Charles Darwin is fondly remembering his return journey from the Galapagos Islands in 1836 on the H.M.S.Beagle.  As he ponders the sights that he had seen, nature and its glorious beauty contrasted against the stark reality of survival among the species, he remembers how he had begun to weave in his mind an all encompassing theory that just might explain the origin of life.  Seeing is believing, and Mr. Darwin had carefully observed and documented the finer aspects of differentiation among the species that would appear to allow for better survival.  Just as the predator always picks out the weakest at the watering hole of life, so too these species, that had adapted to their environment by way of innovative changes by some unknown mechanism, seemed to have been put in a better position for survival in comparison to others.

But what Mr. Darwin does not know is that even as he tries to recapture the fading vision of the Galapagos Islands, an ongoing battle is raging in his own body.  A battle that is just as important for his own physical survival, and in essence, his theory as well.  But he can’t see its machinations.  If he were to know that the body’s defense system against intruding organisms is an amalgam of interdependent chemical-producing cells that are able to be recruited and brought to the field of battle, and that numerous chemicals and proteins, each of which is absolutely necessary for proper defense, must be present, would he still propose his theory of evolution? 

Is it likely that the same man, who had the capability to write one of the most detailed scientific papers, (On the Origin of Species), in which he expounded on many aspects of speciation, and who had such a firm understanding of his own theory and its limitations that he had the foresight later to observe; “If it could be demonstrated that any complex organ existed which could not possibly have been formed by numerous, successive slight modifications, my theory would ultimately break down” after having a working knowledge of how the body defends itself from infection, would still insist that the extrapolation of his theory into what is now known as macroevolution should be considered as a scientific truth? 

I contend that macroevolution cannot explain the development of life, by the mechanisms that it proposes, based on our understanding of how life actually works.  Mr. Darwin cannot be faulted for having entertained his theory of evolution because he was limited by the data available at the time.  Now, over the last century and a half, more information, consisting of the biomolecular basis of life and the human pathophysiology of dysfunction and death as demonstrated by medical science, has come to light.  This too must now be applied to the theory of macroevolution in order to test its validity.  Moreover, it is vital that students of science be allowed to weigh the pros and cons of a theory that seems to be in decline because its proponents cannot present logical explanations to support it in the face of this data.  The lesson at hand regarding the body’s ability to defend itself against infection affords me the opportunity to clearly demonstrate what I think macroevolutionists must be able to prove in order to validate their theory.

Defense- it takes team work!!
Our first defense against infection is the skin.  But if a virus or bacterium is inhaled or swallowed, it then comes up against the lining of the respiratory or gastrointestinal tract which is called the epithelium.  The epithelium acts like skin in that it is a mechanical, chemical, and immunological barrier to foreign invasion of the body.  There are inhibiting antibodies in the mucus secretions of the epithelium that help to kill off many would-be invaders.  But if the aggressor is able to breach our defenses and penetrate below the surface of the epithelium, then there are other cells that fight them off by neutralizing, and then engulfing and killing them.

But if the infection is able to get beyond these first two levels of our defense, then it can spread into the lymphatic system and possibly on to the bloodstream.  The lymphatics are basically an overflow drainage system that picks up fluid from the capillaries.  Eventually this lymphatic fluid drains back into the circulation.  However, it is through this lymphatic pathway that infections can spread and there are sentinel watchtowers along the way, called lymph nodes, that are involved in trying to stop the infection from spreading.  These nodes contain cells that are capable of mounting an immune response to invasion by being able to eventually produce large amounts of specific antibodies.  These antibodies are capable of distinguishing these intruders from normal tissue and thereby initiate the defensive response that results in their destruction.

The body’s ability to protect itself from infection is indeed very complicated.  So much so that whole textbooks have been written on this subject alone.  For the purposes of this discussion I would like to introduce you to some of the major players that defend the body against infection.  I’ll then show you what happens when any one of these players is either non-existent or dysfunctional in order to prove the irreducibly complex nature of the defense system in the body.  Then I’ll go into some of the specifics of how each of these players are able to do their jobs while detailing the components necessary for their proper function.

Immunity-here’s the starting line-up
The immune response is a highly regulated system that involves several different organs, cells, and molecules.  The primary cell that initiates the immune response is the lymphocyte.  Some lymphocytes originate from the bone marrow, but most of them come from stem cells that originated in the bone marrow but that mature into lymphocytes in the lymph nodes, the spleen and the thymus gland, the latter being a lymphoid body that resides in the chest, not to be confused with the thyroid gland which is in the neck. 

There are basically two types of lymphocytes.  There’s the B-Lymphocytes which we will see do a lot of their work in the bone marrow by making the specific antibodies that are capable of identifying intruders.  And there’s the T-Lymphocytes, that have their origin from the thymus, some of which help B-Lymphocytes grow by stimulating them at the right time, and others that have the capability of killing virus infected cells.

Another very important part of the body’s defense system consists of over 20 different plasma proteins that are collectively known as the complement system.  Complement proteins consist of a series of enzymes that are present in the bloodstream in an inactive form that when stimulated will cause a cascade of molecular reactions, much like the coagulation cascade, which will result in the destruction of bacteria or fungi that have been marked out for death by antibodies. 

Finally, the last player that I’m going to introduce to you is the phagocytic cell which is very important for defending the body against foreign invasion.  Phagocytosis is the process by which a cell is able to literally swallow up and chemically digest and destroy foreign intruders that would try to infect the body.  The two commonest cells that perform this vital task are the neutrophils and the macrophages.  The neutrophils are the commonest phagocytic cells in the bloodstream.  They represent about 60% of the white blood cells that are in the circulation at any given time.  Macrophages are distributed throughout the body and they can be found in the blood, the liver, lymphoid tissue and in the connective tissue.

The way that this system works is that the antibodies identify and bind to a foreign invader, such as a micro-organism, and that starts a chemical response that ultimately results in the destruction of the intruder.  The antibodies and complement work in tandem to help weaken the aggressor while at the same time stimulating the phagocytes to come and engulf and digest it.  The combination of antibodies, complement, and the phagocytic cells, together represent a formidable defensive force to be reckoned with in the body.  However, clinical evidence has shown that if any one of these components is absent, or functionally impaired, the body cannot mount an adequate immune response and is then at high risk of dying from infection.  But before we can understand how the dysfunction of any of these components can cause various immunodeficiency syndromes, we first need to understand how these three components of our immune system actually work.

Antibodies are plasma proteins of the globulin class, also known as immunoglobulins.  They are made from cells derived from the B-lymphocyte (B-cell).  Each of these cells makes only one specific antibody.  The antibody itself consists of four chains of amino acids chemically bonded to each other.  They are configured in the shape of a “Y”  having two identical smaller light chains and two identical larger heavy chains forming each side of the “Y” (see Figure 1). 

Figure 1. Note the Fab's (antigen binding fragments) at the top of the "Y" which attaches to the invading micro-organism and the Fc (constant fragment) which attaches to complement and phagocytic cells. In addition, note the variable shapes of the antigen binding sites which will act as a receptor site for an antigen that is contained on the invading micro-organism's cell membrane, much like a key in a lock. Finally, note that the Fc piece consists of only two identical heavy chains which are chemically bonded together,while the Fab pieces consist of identical light chains and heavy chains which are likewise chemically bonded together.

A foreign molecule containing different chemical structures found on the surface of an invading organism is called an antigen.  The tips of the “Y” shaped antibody molecule consist of different amino acids which form an antigen binding site.  Therefore, this part of the antibody is called the Fab fragment (antigen binding) and is capable of identifying and binding to a specific configuration of foreign chemicals found on the surface of an intruder.

The amino acid structure that makes up the base, or stem, of the “Y” shaped antibody molecule remains constant and therefore is known as the Fc fragment.  This part is used by complement, and the other cells of the immune system, to identify foreign particles that have been marked out for destruction by the already attached specific antibodies. 

The DNA in the body is pre-programmed to produce about one million different heavy chains and about ten thousand different light chains, each with their own distinct binding sites.  Since each B-cell produces only one specific antibody that consists of two pairs of identical heavy and light chains joined in a “Y” shape to produce a specific combination of binding sites, you can see that the body is therefore capable of making over ten billion, (one million times ten thousand), different antibodies each with a distinct combination of binding sites.  This gives the body a wide array of specific sentries that are capable of  detecting specific chemical entities on various invading troops. 

Now don’t forget that a given intruding organism may have several different antigens on its cell surface that can be identified by a given specific antibody.  Therefore, it has been estimated that out of the ten billion different B-cell lines, each with its own specific antibody, that one in about one hundred thousand is capable of identifying a given intruder. The only problem with this is that usually when invasion by a foreign organism takes place, there are literally millions of organisms running around doing destruction.  The body’s ability to identify foreign invaders by having billions of specific antibodies being present so that at least one in one hundred thousand will be able to recognize the invader is all well and good.  But that won’t match up to the millions of invading organisms in the body.  The answer to this life-threatening problem lies in the body’s ability to “turn on” specific B-cells so that they can produce enough specific antibodies to stem the tide.

The way that the body does this is very eloquent and mind boggling.  Remember that each B-cell is capable of making only one specific antibody. It is the starting point for antibody formation, but it is not the final processing unit.  There are about one hundred thousand identical specific antibodies with special connectors that are on the cell membrane of a given B-cell.  (see Figure 2)  At this stage the antibodies are locked onto the B-cell and are not free to roam throughout the circulation.  It’s the B-cell, with its membrane-attached specific antibodies, that travels throughout the body trying to grab on to an invading organism by chemically linking up with its specific antigen counterpart.

Figure 2. The key thing to note in this figure is that the antibody (see Figure 1) is attached to the cell membrane of the B-Lymphocyte and is, therefore, at this stage, not free to roam by itself throughout the body searching for an antigen to attach to.

The antibodies located on the B-cell membrane are capable of flagging down and attaching to the intruder.  When the intruder locks onto the Fab piece of the antibody, with the help of calcium and the microstructure of the B-cell,  pieces of it are chopped up and then brought back to the cell membrane surface to expose this antigen to a passing  helper T-cell

Keep in mind that the body does have a mechanism for recognizing itself.  This is called  the HLA (Human Leukocyte Antigen) system, which is the term used in humans for the major histocompatibility complex (MHC) that is present in all vertebrates.  It plays a critical role in allowing the T-lymphocytes to discern between molecules that are “self” and those that are “not-self”.  One class of MHC proteins are found on the surface of most of the cells of the body allowing them to be identified as “self”.  Another class of MHC proteins are involved in exposing parts of foreign proteins (antigens) to the passing helper T-cell in order to regulate antibody production as described here.  And a third class of MHC proteins includes the complement system, described below, which is vitally important for the defense against micro-organisms.  

If the helper T-cell identifies the antigen as being foreign and in need of destruction, it will secrete a chemical messenger called a cytokine which will stimulate the B-cell to start to grow into a lymphoblast.  The lymphoblast essentially forms clones of the originally stimulated B-cell by either migrating to the bone marrow where they eventually become plasma cells, or remaining in the lymphoid tissue as memory cells. (see Figure 3)  

Figure 3. The activation of a B-Lymphocyte occurs when the antibodies on its surface attach themselves to an invading micro-organism and then are able to present the antigen on the cell membrane of the invader to a passing helper T-Lymphocyte which identifies it as being foreign and in need of destruction. The helper T-Lymphocyte then secretes a chemical messenger, called a cytokine, which stimulates the B-Lymphocyte to produce many clones of itself. Some of these are destined to be plasma cells that will produce billions of specific antibodies, like the ones that were on the original B-cell's surface, that are free to roam throughout the body in search of antigen to attach to. And others will remain in the lymphoid tissue as memory cells that are primed for the next invasion.

It is the plasma cells that are capable of making billions of specific antibodies that target this specific antigen on the intruder that are eventually released into the bloodstream and can lock onto the invading organisms.  This results in the primary response of the immune system.  And if the body is ever exposed in the future to the same organism or another one with an identical antigen on its surface, then the memory cells, which are highly sensitive to even low levels of antigen, are capable of mounting a secondary response by virtue of having already been primed from the first invasion.

A quick review of how the body is able to massively produce a specific antibody against a specific antigen in order to protect itself against infection shows both irreducible and specified complexity.  Each component:

Antibodies themselves are usually not capable of destroying the invading organisms, often requiring the help of the complement system and the phagocytic cells, namely the neutrophils and the macrophages.  In fact, the antibodies usually function as simply a signaling system for the other proteins and cells of the immune system to swing into action. 

Nevertheless, medical science, in its understanding of various immunodeficiency syndromes, can point to defects in antibody production that can result in the demise of the body by overwhelming infection even with the presence of normal complement and phagocytic function. 

For, if you can’t identify the invading organisms, the parts of the system that then need to be activated to do the killing are not going to be particularly helpful.  It would be like trying to apply a prevent defense without any available sensory input.  Imagine trying to stop the other team from scoring if you can’t see, hear, smell or feel their presence on the playing field, ice rink or basketball floor.  Without the body’s ability to “sense” the invading army of foreign troops and marking them out for destruction, you might as well kiss your life good-bye.

Two of the commonest  examples of antibody-related immunodeficiency are:

Patients with these conditions are prone to severe life-threatening infections and other immune related diseases, the likes of which would not have allowed for survival.  Clearly, the production of specific antibodies in response to a specific antigen on an invading organism is absolutely necessary for life.

When antibodies attach themselves to an antigen on the surface of the cell membrane of an invading organism this raises a red flag for something called the complement system.  Don’t forget that the antibody has two connecting ends at the top of the “Y”, each called the Fab, that allows it to stick to the antigen.  But the antibody also has the bottom, or stem part of the “Y”, called the Fc piece. (see Figure 1)  It is by way of this Fc fraction that the other parts of the immune system that are needed to destroy the invader are accessed.

The complement system consists of over twenty different proteins which are made in the liver.  Together, they are involved in either the direct killing of invading organisms, the attraction of other cells to help in the carnage or clean-up operation, and for internal regulation of the killing process so that it doesn’t get out of control and is readily available for future attacks. 

In a similar manner to the clotting factors, the complement system contains proteins that have the ability to be converted, under the right set of circumstances, into enzymes that react with each other by a domino effect to finally produce a killing machine that is able to bore a hole through the cell membrane of the intruder.  As a by-product of these reactions, the nearby capillaries become more permeable allowing fluid and fighting cells to come to the battlefield.  In addition, as the battle rages, certain chemicals and molecules are released into the surrounding fluid which attract other cells to help kill off or clean-up what is left over from the battle.

The first component of the complement system that “complements” the effects of antibodies is called C1.  But C1 itself consists of three molecules called C1q, C1r and C1s.  C1q has the ability to bind to the Fc piece of antibodies, particularly when they are attached to antigens.  This is how the “recognition” phase of the destruction of the invader begins. Once C1q attaches to the “antibody-foreign protein complex”, this causes it to change its chemical properties.  When this happens, with the help of calcium ions, C1r and C1s will bind very tightly to the transformed C1q and together they will become “activated C1” also known as the “recognition unit”. 

Now we have “activated C1” attached to the Fc piece of the antibody that is attached to the invading organism.  The C1s component, which itself has enzymatic activity, now reacts with C4 and C2 to form a molecule known as “activated C4b2a”.  This enzyme is able to cleave C3, and the C3b component joins it to form “C4b2a3b” which itself is another enzyme that cleaves C5.  This creates the major active component called C5b.  This molecule then eventually joins up and forms C5b6789 which is known as the membrane attack complex (MAC) that has the capability of chemically punching a hole in the cell membrane of the invading organism thereby compromising its ability to control its internal environment, which can result in death.  (see Figure 4). 

Figure 4. Note: C1 starts the recognition phase by binding to an antibody-antigen complex which results in the recognition unit. MAC is the membrane attack complex.

Not to overcomplicate things but there is an alternative pathway for activating complement which is independent of antibodies.  This involves the ubiquitous presence of C3b which itself is capable of binding to the cell membranes of some intruders.  Once this occurs other molecules called  Factor B and Factor D join in with C3b to eventually cleave C5 and then everything goes on as before to form the MAC.

A quick review of all of the components needed for this to work shows that the whole system has irreducible and specified complexity.  You need the Fc piece, all of the components to produce “activated C1” which then starts the cascade of events, in the presence of calcium ions, that ultimately leads to the MAC which is designed to eliminate the aggressor by specifically boring a hole into its membrane.  If even one part is missing, the whole system fails.  Proof of this can be found in medical science’s knowledge of rare inherited deficiencies of complement which often results in serious and life-threatening infections and other immune-related diseases despite having normal antibody and phagocytic cell function. 

So far we’ve reviewed how the specific systems that allow for antibody and complement function in the body have irreducible and specified complexity within themselves.  But by each of them being absolutely necessary for total body immune function, resulting in survival capability, this also demonstrates irreducible and specified complexity for our entire defense system.  Let’s go on to see where the phagocytic cells fit in to this game and consider what happens to the body if there aren’t enough of them or they aren’t functioning properly.  Remember, all experience tells us that, by definition, the more complex a system is, the easier it is to break down, and the less likely it is that it could have come into being one step at a time by the random forces of nature.  This is one of the major underlying premises behind the Intelligent Design Movement. 

The effector, or phagocytic cells, are capable of literally swallowing up and chemically digesting and destroying invading cells.  The two commonest phagocytes in the body are the neutrophils and the macrophages.  Neutrophils start off in the bone marrow and when they mature they head out into the bloodstream as white blood cells.  The macrophages are distributed throughout the body in the blood, bone marrow, liver, and lymphoid and connective tissue.   

These cells can be attracted to the areas of infection by specific chemical messengers that are released, for example, by activated T-cells, and also by toxins and other chemicals that are related to cellular and protein breakdown such as C3a and C5a which are the by-products from the complement cascade that are not involved in forming the MAC. (see Figure 4) Once they are on the scene, these cells are able to lock on to the invading organisms because they both have receptors on their cell membranes for the Fc piece of the antibody molecule and for the C3b molecule derived from the complement system.  Since the intruder is usually covered with antibodies and C3b molecules, this enables the phagocyte to bind the microbe to its cell membrane and then ingest it.  It does this by using the chemicals that are present in the many granules that it has within its cytoplasm. (see Figure 5)

Figure 5. Once the phagocytic cells (white blood cells and macrophages) are attracted to the battlefield by various toxins and chemical messengers, they lock onto their prey with the help of their membrane receptors for the Fc piece of antibodies and the C3b molecule of the complement system. Then they literally swallow up the microbe and chemically digest it with the granules contained within its cytoplasm.

In review one can readily see that phagocytic cell function is dependent not only on the cell having the granules that can enzymatically destroy invading organisms, but also on the ability to be recruited to the battlefield by chemicals and specific factors as well.  In addition it is vital that these cells possess receptors on the cell membrane that allow it to lock onto its prey. 

And in fact medical science can prove this by demonstrating its understanding of the many immunodeficiency disorders involving phagocytic cells.  These range from an outright reduction in the amount of phagocytic cells, such as occurs when the white cell counts in the blood are reduced because of bone marrow dysfunction, problems with phagocytic cell mobility and surface adhesion, and finally abnormalities in phagocytic cell granule function.  All of these conditions manifest themselves by the patient being prone to recurrent life-threatening infections even in the face of normal antibody and complement function.

The Defense Rests
In this column I have tried to explain in simple detail how three of the most important components of the immune system function.  There is evidence for irreducible and specified complexity underlying the mechanisms contained within them.  But more importantly, medical science can point to various life-threatening immunodeficiency syndromes which result from the dysfunction or absence of any one of these three components.  This occurs even when the other two components are functioning normally.  And of course, what I have presented to you here represents only the tip of the iceberg regarding the true complexity of our defense system, all of which is dependent on each other for proper function and survival.  Clearly, any developing multi-system organism with a complex body plan that was even remotely similar to humankind must necessarily have had an intact immune system in place in order to survive on earth.       

Logic dictates that those who promote the validity of macroevolution as a theory that explains the origin of life by one-step at a time transformations by the forces of nature, certainly have a lot of explaining to do.  They must show how every part of the immune system came into existence while still remaining functional and allowing for survival; this in the face of medical science knowing that the absence or dysfunction of any one of its components, such as the main three that I have presented here, will result in death. 

For without a good defense, you’re as good as dead; literally.  And if macroevolution cannot adequately explain how a multi-system organism with a complex body plan could have developed over many generations, one step at a time, this irreducibly complex defense system which requires numerous specified messengers, with the total capacity to properly defend the body, then macroevolution as a theory is itself, dead; literally. 

Next month we’ll look at the only system in the body in which we have some measure of control, in Wired for Much More than Sound (Neurons and how they work).  I hope that you can join me then.  It’s sure to test your wonder as never before.

Dr. G.

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 recently left his private practice and has started to practice 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.

Copyright 2004 Dr. Howard Glicksman. All rights reserved. International copyright secured.
File Date: 6.01.04