From Arthritis to Zoster

Among the many components of a healthy immune system, the complement system – so named because it “complements” antibodies in their attempts to rid our bodies of foreign antigens – serves as one of the principal bridges between innate (“instinctive”) and acquired (“learned”) immune responses. The complement system is composed of a group of enzymes that, when activated, initiate a biological cascade that helps to defend us from infection.

The individual enzymes in the complement pathway are identified with a C and a number (e.g., C1, C2, C3, etc.) based on the order in which they were identified. Over two dozen proteins and protein fragments make up the complement system. 

Complement’s main tasks are to amplify antibody responses, assist in the destruction of foreign cells, clear out aging or dead cells, and remove immune complexes (e.g., antigen-antibody aggregates) that are part of the “battleground debris” resulting from destruction of foreign antigens. In performing its tasks, complement components stimulate the movement of white blood cells (chemotaxis) and induce immune cells to release cytokines and other important molecules.

Many of the complement system’s components circulate through the bloodstream in their inactive forms, called complement precursors or zymogens. These zymogens must be activated by contact with some sort of triggering molecule before the complement cascade begins.

Three pathways of complement activation have been described:

1. Classical pathway
2. Mannose-binding lectin pathway
3. Alternative pathway

The classical pathway can be either antibody-dependent or antibody-independent. This pathway is activated when C1 interacts with antigen-antibody complexes, with certain anions (DNA or RNA from dying cells, heparin, protamine, etc.), with polysaccharides in bacterial cell walls, or with bound C-reactive protein.

The mannose-binding lectin (MBL) pathway is antibody-independent. In this pathway, complement is activated when MBL, a serum protein, binds to mannose molecules on bacterial cell walls. This creates a molecular complex that resembles activated C1 and initiates the complement cascade.

The alternative pathway is activated when C3 is cleaved by various components from the cell surfaces of microorganisms (yeasts and bacteria) or by conglomerates of antibodies. Cleaved C3 then interacts with other proteins in the bloodstream, thus initiating the complement cascade.

All three pathways are ultimately regulated by both inhibitory and stimulatory molecules, and they all converge into a common pathway that results in the formation of a membrane attack complex (MAC). The MAC is an aggregate of activated complement that punches holes in the membranes of foreign cells, resulting in their destruction.

Another critical function of complement is its ability to act like immunologic “butter.” Whenever a foreign antigen gains access to our bodies, complement quickly coats the potentially harmful invader – a process called opsonization – and makes it appear “tasty” to circulating immune cells. The foreign antigen is then more efficiently consumed due to the presence of complement. Once consumed by a white cell, the antigen is presented to surrounding immune cells so they, too, will recognize and respond to the invader.

Finally, fragments of activated complement serve as molecular messengers to educate immature immune cells. By adhering to specialized receptors on the surfaces of various cells, complement assists in antibody production and the development of immune memory. Henceforth, when a given antigen returns, a defensive response can be initiated much more quickly.

Maryland-based NeuralStem, a biotherapeutics company engaged in the development of neural stem cells for treating diseases of the central nervous system, has just begun patient trials to determine the safety of spinal stem cell injections. This represents the first such trial in the United States and marks a major milestone in the use of stem cells for treating serious human conditions.

Amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease, is a progressive degenerative illness that eventually destroys the nerves that control voluntary muscle movement. Without nervous impulses to control muscle movement and maintain muscle integrity, individuals with ALS eventually lose the ability to initiate and control all voluntary movement, including efficient breathing activity. Death from ALS, which typically occurs within two to five years of diagnosis, is usually due to respiratory failure or pneumonia.

The specific cause of ALS is unknown, although immune dysfunction may play a role. Mitochondrial disorders, DNA abnormalities, exposure to toxic or infectious agents, and cellular oxidative stress have all been proposed as contributing factors to this disease.

Scientists at NeuralStem have demonstrated that “neuro-adherent” stem cells can survive, integrate, and differentiate when placed in the central nervous systems of animals. These cells, when used in animals with ALS, exert a protective effect – essentially forming functional “patches” over damaged nerves – that delays the progression of the disease.

Now, with approval from the FDA, NeuralStem has injected its neural stem cells into the spinal cord of a 60-year-old man with advanced ALS. The company, in conjunction with researchers at Emory University, has chosen to begin trials in people with more serious disease, because these subjects are less likely to lose additional function if the stem cell transplants cause unanticipated adverse effects.

In short, this initial trial is not designed to test the treatment’s efficacy; it is meant to evaluate the safety of spinal stem cell injections. Up to 18 patients will be recruited for this phase of the investigation.

With time – assuming that NeuralStem’s cell lines don’t precipitate untoward side effects – this therapy will be directed toward alleviating or even curing a devastating disease. Additionally, other serious disorders of the central nervous system will lend themselves to similar approaches.

In the end, stem cell therapy (regardless of cell line origin) has the potential to allay a great deal of human suffering, improve the quality of life for countless individuals, and reduce the financial burden of disability that weighs on our economy.  

Let’s face it…unless you’ve lived under a rock for the past ten years, you already know that over 60% of Americans are overweight or obese. On the basis of statistics alone, two out of every three people reading this page are struggling with their weight – maybe more, if you consider the bias introduced by internet search engines.

Everyone who is overweight has also already heard the party line: In order to shed those extra pounds, you have to cut down on your calories and get off the couch; you can’t lose weight unless you burn more energy than you consume; and so on, and so forth…

What many people don’t know, and what is still unsettled in the minds of scientists who study the obesity issue, is how much influence our immune systems have on weight gain…and, by default, on weight control.

Enter the “hygiene hypothesis.” This theory postulates that many of our modern-day health issues – from asthma and allergies to rheumatoid arthritis and fibromyalgia – are rooted in our lack of exposure to a sufficient number of germs when we are very young. Such a notion flies in the face of conventional thinking, which holds that improved sanitation, antibiotics, and other trappings of contemporary living are the main reasons we’re all living to be 80 instead of 35.

But our sanitized surroundings may actually be contributing to some health problems along the road to that golden “fourscore-and-then-some” milestone. There’s some pretty compelling evidence that our immune systems first learn to not only protect us from our environment when we are in infancy; they also develop the critical state of balance that prevents them from beoming our antagonists later in life.

Apparently, a great deal of our “immune education” requires the existence of a robust population of probiotics in our intestinal tracts, which leads in turn to an ample supply of immune messenger molecules in our bloodstreams.

Probiotics are “friendly bacteria” that live in our environment – most of them exist in the soil – and their colonization of the human gut stimulates the type of immune response that keeps us healthy throughout our lives. Proponents of the hygiene hypothesis contend that most infants in industrialized nations do not receive their requisite “dose” of probiotic organisms at a time when it will do them the most good.

How does this relate to obesity? Well, research has already demonstrated that obese individuals exhibit highly unusual responses to immune challenges:

• People who are overweight are much more likely to succumb to certain infections due to impaired immunity (abnormally low activity of T cells and NK cells).
• Obesity interferes with the production of cytokines that serve as immune messenger molecules; hence, an appropriate response to an infectious organism or suppression of a hyperactive immune system does not occur in a timely fashion.
• Obesity dampens the effects of hormones that usually trigger immune responses. Thus, infections can gain a foothold – or a revved-up immune response can continue unchecked – before the immune system’s “damage control” function can intervene.

Conversely, several recent studies have demonstrated that obesity – and many of its consequences – may actually be driven by inappropriate activities within our immune systems. In short, obesity (like coronary artery disease) is an inflammatory disorder.

It is probably premature to assume that immunomodulation (i.e., therapies aimed at balancing the immune system) will become a mainstay in the treatment of obesity. However, a great deal of scientific effort is being directed at this very idea; I have no doubt that there will soon be medications on the market for individuals whose obesity can be partly or wholly attributed to immune imbalance (although tests designed to detect the specific immune derangements that cause obesity aren’t widely available).

In the meantime, we should include a good probiotic supplement in our daily routines; no one knows for sure if reestablishing a normal population of bacteria in the gut will “repair” an unbalanced immune system, but it’s certainly reasonable to assume that it will help. Live-culture yogurt is one way to acquire some probiotics, but the number and viability of organisms in yogurt cannot be ensured. Individuals who are immunocompromised should use probiotics with caution.

Additionally, people who are trying to lose weight – particularly those whose best efforts aren’t yielding the expected results – should really consider adding some immune-balancing messenger molecules to their programs. The only such preparations that are available to the general public (and that have sufficient scientific support for their use) contain transfer factors. Transfer factors were discovered over 60 years ago, and hundreds of scientific articles attest to their effectiveness.

Only one company, 4Life Research, has the expertise – not to mention the worldwide marketing rights – to ensure the quality of transfer factor products. They’ve even coined a phrase for their preparations: “Transferceuticals®”  

Specifically, take a look at Transfer Factor Tri-Factor Formula, Shape-Fast Ultra (for people who want to improve the caloric burn) and NutraStart. All of these formulas contain healthy doses of transfer factors.

Good luck in your weight-control efforts, and don’t give up!!