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Topics in Depth

The Theme of Fitting It All Together in Animal Systems

The Puzzle of Life

Science would be a whole lot easier if each system minded its own business. Sorry, they don't. They are all up in each other's business, but they mean well. 

In fact, these three systems we've been discussing (immune, endocrine, and nervous) really like each other, and get together for mixers all the time. It usually ends up being a two-way street, too. Maybe the brain talks to the immune system through the endocrine system, then the immune system responds and affects the brain. 

Since most of these processes are circular, it can become a chicken or egg situation: trying to figure out what causes what. Did the brain activate the immune system or did the activated immune system affect the brain? There's no easy answer, that's for sure; heck, researchers don't even have the whole picture figured out yet. But just to get a general idea of what we're talking about we'll go over some of the major ways these systems communicate with each other. These topics are totally awesome, and we imagine you'll be thinking about them for days to come. 

Just to have an example, let's suppose the immune system senses a dangerous threat, like cancer cells. Part of the immune response's job is to release cytokines that activate local innate responses and the adaptive immune system. But when the cytokine concentration gets high, they head away from the infected area, eager for a new adventure in the bloodstream. It's these cytokines that alert the nervous and endocrine systems of the cancerous threat. 

To talk to the brain, cytokines activate sensory nerves within the periphery, and send electrical signals to the brain. Some of the cytokines can get into the brain themselves, and activate the hypothalamus, for example. Either way, the immune system is initiating a conversation with the nervous system, pleading for help. 

But say the cytokines were in a fight with the nervous system (the nervous system flirted with the immune system's boyfriend at the homecoming dance) and wanted to ignore it completely. It's totally doable since cytokines can also act on the endocrine system itself by activating the pituitary and adrenal glands. 

Once the cytokines have activated certain parts of the brain, there are two primary ways that the brain can respond to the immune system. One is through the autonomic system. Because the autonomic system talks to immune organs like the bone marrow and thymus, the brain has some control over whether or not immune cells get produced and activated. If those cytokines asked the brain nicely, the autonomic system might activate the bone marrow and thymus to release more immune cells to combat those pesky cancer cells. 

The other way the brain talks to the immune system is through the endocrine system. Since the hypothalamus is simultaneously a part of the brain and the endocrine system, it orchestrates a lot of the communication between the nervous and immune systems. But it usually takes lots of endocrine glands, and a hormone cascade pathway, to translate a nervous system message into something the immune system can understand. The thyroid gland is often involved (he's kinda nosey), as are the pituitary and adrenal glands. Any gland can have a role in the neuroendocrine communications. 

If cancer cells instigated all this conversation in the first place, it's likely that the endocrine pathway called the hypothalamus-pituitary-adrenal (HPA) axis gets activated since it's a super hero when there's some sort of a stressful situation—this would include the presence of cancer cells. (Here HPA comes to save the day.) The adrenals don't only get activated when we are emotionally stressed, but internal stress puts them to work, as well. 

When the hypothalamus hears from cytokines or the brain that there's a stressful situation going on somewhere, it whips up a batch of corticotrophin releasing factor (CRF). CRF heads to the pituitary to explain the dealio and to get to work on some adrenocorticotrophic hormone (ACTH). ACTH then skips down to the adrenal glands to make a rush order on some cortisol. Complicated—we know. 

Cortisol is the hormone that communicates with the immune system. It's released by the adrenals, so it's important in the stress response. Since it's a type of glucocorticoid, cortisol regulates blood sugar, but also affects the immune system. If the stressful situation is short-lived, cortisol usually stimulates leukocyte release to help the immune system out. In more chronic, prolonged stresses, cortisol also has anti-inflammatory properties and acts as an immunosuppressant. Specifically, cortisol prevents lymphocytes from dividing, so it keeps the amount of reinforcements in check. 

Why would an activated immune response activate a pathway that suppresses it? If things suddenly get out of hand, cortisol gets released to quiet the immune system down to an appropriate level. It's a way to calm down an overactive immune system. It's sort of how the suppressor T cells of the cell-mediated immune system work. 

This is just one example. There are a lot of different ways these systems talk to one another, and it doesn't have to start with the immune system every time. Maybe the peripheral nervous system senses a threat and the brain activates both the immune and endocrine systems to help out. If the systems are superheroes, this is an Avenger's sequel.

When Things Go Wrong

There's also the possibility that something can go screwy in one system. Because all three are so closely related, it affects another system. What happens when something goes wrong in one, or many, of these systems? 

In each of these systems (the immune, endocrine, and nervous), there are lots of parts and pieces associated with any given number of biological actions. But if just one of those pieces gets out of whack, that biological process can't happen as it's supposed to. The consequence could be big (you can't control your bladder during a final presentation) or small (you must resist your favorite cookies). No matter the effect, it just goes to show how important all these little pieces are.

We'll go over some human diseases, but many also occur in animals for the same reasons they occur in humans. It's just harder for most of us to associate these diseases with Fido since he can't talk to us. If you're hearing from your pet pooch that he's not feeling so hot, you might want to seek some professional help. Hopefully he can avoid the cone of shame. 

As we go through these different diseases, notice that they connect multiple systems. Because these three systems rely on each other so often, when something goes wrong in one place, its off-kilter impact is often felt in another place.

Diabetes

One of the most common diseases of the endocrine system is diabetes mellitus. It affects more than 20 million people in the US alone, and is all due to the body's inability to regulate blood sugar levels properly. As a result, people with diabetes suffer from really high blood sugar levels and a whole host of related symptoms. 

Insulin is the hormone that's released from beta islet cells of the pancreas in response to high blood sugar levels. In healthy people, insulin tells the liver that the body has a wee bit too much sugar floating around, and that it should suck some up for storage to reduce the blood sugar level. But if a person is diabetic, he or she cannot produce enough insulin to get that message across, or the body has just stopped listening to it, or some combination of both. If one part of the body suddenly stops paying attention to another part that's busy waving a red flag, it can cause some serious issues. 

There are two types of diabetes: Type I and Type II. The first type primarily occurs in children and young adults, and it's caused when the pancreas makes insufficient amounts of insulin, or none whatsoever. Those with Type I diabetes have to carefully monitor their blood sugar levels since they don't have insulin on hand to even things out. They take synthetic insulin whenever it gets too high.


Syringe. One way a diabetic gets his or her insulin is through injection of a synthetic insulin.

Type I diabetes is also often thought of as an autoimmune disease, where the immune system sees healthy cells as infected, and strikes out against them. For whatever reason, the immune system fails to recognize healthy islet cells. Instead, it sees them as foreign, and attacks and kills them like it would kill the cold virus. No functioning beta islet cells means no insulin production. 

Type II diabetes occurs when the body becomes resistant to insulin and no longer responds properly when it's released. Although insulin is still released when blood sugar levels get too high, the liver doesn't care, and simply doesn't respond to it. With a bit of attitude, it says, "Talk to the hand, 'cause the liver ain't listening." This diabetes type has a hereditary component, and is common in overweight adults. Sometimes synthetic insulin is used to help keep blood sugar levels nice and smooth, but most times the treatment is just a major dose of healthy living, eating right, and exercising. 

Since diabetes causes prolonged exposure to high blood sugar levels, patients often get blurry vision, are excessively hungry, and pee a lot (the body's way of getting rid of the excess sugar). If it remains untreated, more serious symptoms arise: blindness, infections on the feet, and nerve loss.

Parkinson's Disease

If you like tear-jerkers, check out Love and Other Drugs. It's a movie with Anne Hathaway and Jake Gyllenhaal, and it's all about how they deal with her Parkinson's disease.

Parkinson's disease is one of the most common diseases of the nervous system in adults, affecting about 1% of the population over 60.

In Parkinson's disease, the neurons that release the dopamine neurotransmitter into the basal ganglia (an area of the brain that's in charge of voluntary movement) slowly die. When the basal ganglia doesn't get enough dopamine (or none at all), initiating movement becomes really difficult, and patients have trouble doing so. Parkinson's patients also suffer from shaking, muscle rigidness, and constipation (since it's not just the skeletal muscles that are affected, but the muscles used to make BMs, too). Because this part of the brain only controls voluntary movements, patients still have reflexes. So while they have a tough time picking up a pencil, their knee still jerks when a doctor taps it.

Although no one knows for sure what causes these dopamine-producing neurons to die, scientists do know that they die slowly over time. So it's only when the majority of them have died that symptoms show up. No one is quite sure what causes the disease, although some think certain chemicals or a genetic abnormality are the culprits. There is some evidence that the immune system has something to do with the neuron deterioration since there's inflammation and loads of T cells in the area.

There are a few treatments for Parkinson's disease, but since we can't regrow dopamine-producing neurons in the brain, they only treat the symptoms and not the underlying cause. The most common treatment is to increase the brain's dopamine levels with a drug called L-dopa. It gets converted to dopamine when it reaches the brain. 

Multiple Sclerosis

In Type I diabetes, we saw how a problem within the immune system causes a problem within the endocrine system. In Multiple Sclerosis (MS), a problem within the immune system causes major problems in the nervous system. Because the nervous system controls many different areas of the body, there are major problems elsewhere, too.

Like many diseases, we don't know what causes MS. There seems to be a genetic factor since it runs in families, but it also appears that the environment plays a role, too, since the disease is more common in certain parts of the world.

Whatever the cause of MS, the immune system incorrectly sees the myelin that covers axons in the nervous system as foreign and unwanted. It attacks the myelin, and degrades it. When an axon isn't coated in myelin, electrical signals move much more slowly, and sometimes they stop moving altogether. Because neurons can no longer properly communicate with one another, the first sign of MS is usually declining neurological function. Because the brain can no longer send messages to the rest of the body, other symptoms include muscle spasms, blindness, reproductive problems, and hearing loss.

It's tough to cure a disease when you can't pinpoint what causes it in the first place. The only treatments out there attempt to curb symptoms and (hopefully) prevent other symptoms from getting worse. Since the disease starts out as a problem with the immune system, many of the drugs target this symptom to decrease inflammation. But since the disease targets the nervous system, other drugs work to try to regrow or replace the missing myelin. Since MS causes a lot of motor and muscle problems, physical therapy is usually a key part in treating the disease.

Brain Snack

There are two types of diabetes: Type I and Type II. The first type primarily occurs in children and young adults, and it's caused when the pancreas makes insufficient amounts of insulin, or none whatsoever. Those with Type I diabetes have to carefully monitor their blood sugar levels since they don't have insulin on hand to even things out. They take synthetic insulin whenever it gets too high.

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