Inflammation II: The Biology Behind an Immune Response

In an earlier blog post, I developed a clinical picture of the ways in which inflammation presents itself to the clinician.  If your patient presents with a cut on the hand, a broken bone, or a known food allergy, or the flu, it is easy to see that the inflammatory process is in action.  Molecular signals from the environment have activated the immune system and inflammatory chemicals have been released locally (pus and redness around a cut) or systemically, meaning throughout the whole body (aches and pains, fevers, nausea).

The body basically has two collaborative immune systems, the innate or cellular immune system, and the acquired immune system.  Innate immunity is characterized by local tissue destruction, indiscriminate release of toxic chemicals, and an acceptance of some “collateral damage” in the form of damage to healthy, native tissue.  The innate immune system is driven by cells known as macrophages, which are the first line of defense in the fight against abnormal molecular signals.  With the solidarity of an ‘MHC’ classification- akin to an identifying molecular armband worn by members of the same cellular “team”- this class of cells is always first into the fray.  But they’re the grunts, the edgy boarder guards; they have a quick trigger to heave a cellular toxic grenade or two; to “shoot first and ask questions later.”  This initial immune response, starting within minutes to hours after an exposure, is often indiscriminate, leaving a significant amount of damaged “normal” tissue in its wake. 

I like to imagine the innate arm of the immune system as the infantry, characterized by cruder weapons, frequent skirmishes, and hand to hand combat.  In the heat of the battle, the macrophages can rip off an invading molecule’s identifying “armband”, and along with cellular signals known as cytokines, pass along information to central command about the biological challenge at hand.  T helper cells, the next level of immunity, then make the determination as to whether we have seen this environmental molecule before, its degree of severity, if the assault should continue on the ground, or if we need to recruit the forces of the acquired arm of the immune system.  The acquired immune system is in charge of the release of antibodies.  An antibody’s job is to seek out invaders that are specific to, and recognized only by  that antibody.  If the innate immune system is the ground charge, the antibodies are the drones.

These antibodies, protein “drones”, float through our physiology to pick out a specific invader or a known criminal; they are peering through the windows in our tissues looking for a previously encountered bacteria, an established food sensitivity, or a known “dangerous stranger.”

Once a “dangerous stranger” is positively identified by the immune system, several recourses are available to our body to rid the body of the danger.  The macrophage, on its own accord, can simply gobble up the dangerous invader, whether it is an invading bacteria, cancer cell or toxin via a process known as phagocytosis. 

The next lines of defense are a bit more involved and complicated.  The first-line cells can release inflammatory signals to activate and inform other immune cells.  Some of these cytokines are pro-inflammatory, and go by the names of IL-1 (Interleukin 1), IL-6, or tumor-necrosis factor (TNF).   The macrophages contain chemical weapons within the cell, and when stimulated release small packets of hydrogen peroxide (H2O2), superoxide (O3) or hydrochloric acid (HCl).  These are energetically active molecular species that disrupt the cellular function of the invading organism.  The problem is that if left unregulated, and if perpetual, these molecular inflammatory charges ultimately disrupt components of our own physiology as well.

In many chronic diseases there is evidence of a persistent inflammatory state.   The blood test high sensitivity CRP correlates strongly with the circulating interleukins IL-1,IL-6 and TNF.  The direct measurement of these interleukins is still relatively confined to research facilities, but slowly these blood tests are making their way into more generalized use.  For people with high inflammatory markers that persist over time, the risk unquestionably increases for disease states such as cancer, diabetes, Alzheimer’s disease or cardiovascular disease.

Inflammation is essential to our health by protecting our body from invading organisms such as bacteria, viruses, parasites and toxins.  However when inflammation is excessive and unregulated, or the immune system loses the ability to turn itself off, too much inflammation becomes simply “bad”.

So is inflammation good or bad?  I don’t want my state of inflammation to be too high or too low.  Like the littlest bear, I like my inflammatory porridge to be “just right”.