Darwinism Vs. the real world XXVII

The Body as a Battlefield: Proteins of the Innate Immune System

Howard Glicksman February 3, 2016 5:07 AM

 

Editor's note: Physicians have a special place among the thinkers who have elaborated the argument for intelligent design. Perhaps that's because, more than evolutionary biologists, they are familiar with the challenges of maintaining a functioning complex system, the human body. With that in mind, Evolution News is delighted to offer this series, "The Designed Body." For the complete series, see here. Dr. Glicksman practices palliative medicine for a hospice organization.

 Since life takes place in the context of nature, it must not only exist in accordance with physical and chemical laws, but must also protect itself from many of the organisms in its environment. There are a wide variety of microbes that our senses cannot detect and that are always trying to enter our body so they can multiply.

The first line of defense against infection by these microorganisms is the skin and the epithelial tissues that line the respiratory, gastrointestinal, and genitourinary tracts. Without any one of them, our earliest ancestors could not have survived long enough to reproduce. However, if by injury to the body or functional ability of the microorganism, the microbes penetrate into the tissues below, then they come up against the second line of defense: the immune system.

As we've seen already in this series, the immune system can be divided into two parts: the innate immune system that each of us is born with and the adaptive immune system that develops over time as we are exposed to the environment. Each of these systems has its unique cells and proteins, needed for the body to defend against microbial invasion. In my last two articles we looked at some of the more important immune cells of the innate system: the mast cells, macrophages, and dendritic cells, which are the first responders in the tissues, and the neutrophils that travel in the blood and respond to the signal to come to the battlefield. Now we will look at the proteins of the innate immune system and how they work to bring other immune cells to the field of battle, make neutrophils and macrophages more effective, and fight invading microbes.

The plasma proteins of innate immunity, which leak into the tissues when inflammation takes place, are collectively known as the complement system, or sometimes simply the complement, because they complement (complete) the function of its cellular components. The complement system consists of thirty or more proteins that, like the clotting factors, are mostly produced in the liver and enter the blood in an inactive form.

Also, just as with clotting, there is more than one pathway for activation and once it begins, it progresses quickly in a cascading fashion, like falling dominoes. Finally, just as with the coagulation cascade, activation of the complement system requires that two key enzymatic steps take place to unleash its power. Since inappropriate activation of the complement can result in significant injury, the body must make sure that it only turns on when it's needed and stays or turns off when it's not.

Just as the final common pathway for coagulation involves mainly two clotting factors (prothrombin and fibrinogen), so too, activation of the complement system involves mainly two complement proteins called C3 and C5. There are thought to be three chemical pathways by which foreign molecules on the surface of invading microbes triggers complement activation.

All three of these pathways converge to form an enzyme called C3 convertase. C3 convertase, as its name implies, is an enzyme that breaks specific bonds within hundreds of molecules of C3 and converts them into two fragments called C3a and C3b. (It sounds like the scientists who came up with these names must have been brought up on Dr. Seuss's book The Cat in the Hat Comes Back. Remember Little Cats C, D, E, et al.?)

The smaller fragment, C3a, binds to specific receptors on mast cells, which trigger them to release histamine to bring about inflammation and call more immune cells and proteins to the battlefield. The larger fragment, C3b, usually does one of two things. It can attach to foreign proteins on microbes, allowing neutrophils and macrophages to better identify and attach to them by using specific complement receptors. Then they can engulf and digest them or it can join with C3 convertase to form another enzyme called C5 convertase, which breaks C5 into two fragments called C5a and C5b.

Like C3a, C5a, the smaller fragment, triggers inflammation by attaching to complement receptors on mast cells to release chemicals like histamine. C5a also helps neutrophils and monocytes (macrophages), pass through the capillaries and attracts them to the field of battle by chemotaxis. The larger fragment, C5b, acts as an anchor to which several specific complement proteins attach to form what is called the Membrane Attack Complex (MAC). The MAC is a weapon made up of these complement proteins that literally drills a hole through the cell membrane of the microbe to kill it.

However, just as in clotting, where inappropriate activation of the system is very problematic, so too the body must be able to control the explosive power of the complement system. To control hemostasis, the body has to have enough anti-clotting factors that can resist coagulation unless significant injury and bleeding takes place. Here as well, to control the activation of the complement, the body has to have enough inhibiting proteins to resist the formation of both C3 and C5 convertase unless a significant infection is present.

When activated, the proteins of the complement system provide the body's immune defense with significant assistance and firepower to fight against resistant pathogenic microbes. Activated complement proteins increase inflammation (C3a, C5a), attract phagocytes to the battlefield (C5a), help them attach to microbes for phagocytosis (C3b), and directly kill microbes (C5b, MAC).

In addition, to prevent tissue damage, the body must have enough inhibiting proteins so that the complement only turns on when it's needed and stays or turns off when it's not. Deficiency of a specific complement protein or one of their inhibitors is rare and usually manifests as either recurrent infection or serious allergic or autoimmune disease. This means that if our earliest ancestors hadn't had enough of most of the proteins that make up the complement system, they never could have survived long enough to reproduce.

Evolutionary biologists observe that certain of the components of the complement system are present in some earlier forms of life and they conclude that its development can be explained by gene duplication. However, not only is the system irreducibly complex, requiring all of the parts to work properly, but there has to be enough of each of the components and their inhibitors as well.

In other words, the body requires a natural survival capacity to produce enough of each component, the control of which evolutionary biologists can't explain and neither can medical science. Now that you know the components of the innate immune system and how they work together to help defend the body from infection, we'll look at the adaptive immune system.