Immune System

The Immune System:

The human immune system is an intricate,dynamic drama or stimulaus and response featuring a cast of of billions of cells,a language understood only by the players,and a setting that includes every scene in the human body.

Cells are living sacks of chemicals. Cells communicate with each other. The language that cells use is spelled out in molecules. The chemical messages that arrive at the cell borders are translated by the cell into commands that alter the cell's own chemistry in some way.

Cells detect these signals when the chemicals combine with specific receptors on the cell membrane,which then relay the information to the cell interior's interior. These receptors are special proteins. Proteins,which can be thought of as locks,they will open up only in response to the right key.

Depending on the chemical message that the unlocked lock lets inside, the cell may respond by switching on or off specific genes or may slow down or speed up the activity.

Through this constant monitoring of the chemistry of the environment, a cell acts in a way in keeping with the messages brought to it from near and far.

The result is a living,active human individual whose countless cells,by responding to what they recieve as chemical commands,react by adjusting their own chemistry.

But,things can,and do go wrong. We face two dangers,one from within the body,the other fromm without. Within each cell the very genes inherited from our parents,can include in their numbers that can bring havoc in the form of genetic diseases.

While many diseases have genetric components,only of which some have been identified,there are other contributing factors required for the expression of disorders such as RA.

There are schools of thought (among others) that RA begins by an attack by viruses and bacteria,( none of which has been proven as the factor.) Some of the protective responses of the body to the arrival of those dangerous organisms mirror some of the same responses that the immune systems of RA make towards their own tissues.

In a normal immune system viruses and bacteria are attacked and destroyed by cells and chemicals. In the case of RA patients,the same efficient weapons are turned against the tissues of the joints and elsewhere,and the destruction wrought,brings pain and disability,if left unchecked.

The reactions of our immune systems require cell workers and chemical messages and also a means of carrying these messages throughout the body. For that purpose we use two quite distinct but interconnected anatomical networks,the blood circulatory system and the lymphatic system.

The lymphatic system is much more than simply another route available for recirculating tissue fluid. It is the essential framework of the immune system,a critical resource for the recognignition of danger a supplier of the tools that defend us against the damages.

Situated along the course of the lymphatic vessels are hundreds of lymph nodes,masses of organized lymphatic tissues, which act as filters through which the tissue fluid,now called lymph,trickles.

Large aggregates of these nodes are located under the arms,in the groin,in the neck,and elsewhere. Several organs including the spleen,the appendix,and the tonsils are masses of lymphoid tissue.

These lymphatic filters are filled with cells that are waiting to detect the slightest hint of danger in the tissues.

If invaders such as bacteria get beneath our epithelium they are met by scavenging cells (white blood cells) such as the macrophages. These scavengers engulf the invaders and eat them. Some of the macrophages slip into nearby lymphatic vessels and are carried in the lymph stream to the nearest lymph node.

There,the macrophages present specific fragments of the remains of the invaders to cells waiting in the node for just such a signal. These presented fragments are the antigens,specific pieces of the invader,usually proteins,that the immuhe system recognizes as dangerous.

Alarmed by the prospect of an attack on the body,these waiting cells spring into action and set off a series of interdependent events that result not only in the production of protein antibodies,specifically manufactured to combat the specific offending antigen,but also part of the bacterial cell itself. The antibodies mark it for destruction.

The newly recruited cell helpers leve the lymph nodes,flow through the lymphatic vessels to the blood and soon arrive at the affected tissues. There,powerful chemical signals persuade the cells to slow down,stop,and work their way through the capillary walls to join the ongoing struggle.

Beginning of the immune response (Simplified ): The problems that leads to RA when some still unidentified foreign agent invades the body of one who is susceptible. The body recognizes the invader as other,and the immune system responds. First on the scene are sentries that are ever alert to invaders.

In the synovial membrane that surrounds mobile joints,these sentries consist mainly of cells known as macrophages. They essentially engulf the invader,chew it to bits,and then strip off tiny fragments that can be used to identify other invaders like it. The alert is given.

One research-scientist has called macrophages the "messenger" of the immune system. They sound an alert and wait for the immune system troops to arrive. It is a war going on in our bodies.
Immune system sentries known as helper T cells are the first to respond. They assess the situation and decide what type of immune system soldier should be called to the scene. At this stage there are no symptoms.
The immune response escalates: Now that the immune system has recognized a foreign invader,it initiates a cascade of events meant to ensure that the invader is destroyed.
The helper T cells call for the soldiers. There are two broad categories of soldiers in the immune system:killer T cells,which can attack an enemy head-on,and B lymphocytes,which manufacture and release antibodies specifically designed to home in on and destroy the foreign invader.
Meanwhile,other changes take place to enable additional immune system cells to reach the area. The macrophages(white blood cells) which originally helped sound the alert about the invader,now help new blood vessels to form.
They are assisted by hormone-like substances called cytokines (they have a good part and a bad side),which enhance and amplify the process of inflammation that has now begun.
Other immune system cells (billions) that are circulating elsewhere in the body home in on the joint,attracted by all the commotion. (simplified analogy) these cells start to accumulate in the synovial membrane surrounding the joint.
Meanwhile,other immune system cells known as neutrophils,aanother type of white blood cell,begin to accumulate in the synovial fluid that fills the joint cavity.
Neutrophils exist as a type of cleanup mechanism at the site of infection,they consume the debris of an immune system assault and any other unwanted particles or bacteria. They do this by releasing digestive substances known as lysosomal enzymes that break down and dissolve their targets.
At the same time another component of the immune system known as the complement system is activated. This unleashes proteins that further speed the destruction of foreign particles by antibodies.
In some ways it sounds like a war is going on. In RA for reasons that is still unclear,the attack not only continues beyond the original goal of destroying virus and bacteria but also escalates.
Many as a billion neutrphils may be circulating in the synovial fluid of the knee that is moderately inflamed. The enzymes they release,once directed at a foreign invader,start to attack healthy cartilage and ligaments.
By this time,you are quite aware that something is wrong in your body. You might feel stiff upon awakening,and it may take as much as an hour or more to limber up (some patients claim it never eases up),for some people,increased fatigue.
If it continues without treatment.--loss of mobility,visible swelling of the joint. Unchecked joints may become deformed, or even become disabled.
Immune cells initiate and control the inflammatory process in part by releasing messenger proteins called cytokines (e.g.,interleukins and tumor necrosis factors ),which act like distress signals to all relevant immune cells.
Specifically, cytokines tells other immune cells to initiate "cascade" reactions that yield hormone-like chemicals called inflammatory mediators.
In RA,the inflammatory mediators that immune cells release in response to cytokine "messengers" include histamine,leukotrienes,and certain prostaglandins. There are different prostaglandins in the body.
These inflammatory mediators make small capillaries wider and "leakier",permitting more immune cells to flood the area,where they release enzymes that dissolve connective tissues.
Normally,inflammation is an appropiate immune response to injury or infection. But RA is charachterized by a ungovernable,ongoing inflammation.
We know that when synovial fluid contains high levels of cytokines,collagen damage and the risk of arthritis is increased-and the cells that send the first inflammatory messages,via release of cytokines,may be distant from joint tissue.
We also know that damage to the synovial capsule corresponds to abnormally low levels of antioxidant molecules,including certain enzymes. Furthermore, damage to collagen correlates with high level os inflammatory messenger molecules in synovial fluid (e.g.,tumor necrosis factor-alpha,interleukin-1 etc. )

This scenario is so much a part of what goes on in RA.There is much more to the complex,long,complicated,equation.

Notes:

We continue to hear about new treatments for RA. However, it seems that so many of the treatments available have side effects. What about the side effects involved in biologics- infection ,MS,and TB.

Some people have side effects to almost any treatment where other people seem to tolerate lots of things, and you can never know in advance.

A lot depends on the patient and how they individually respond to an agent. Some people have side effects to almost any treatment where other people seem to tolerate lots of things, and we can never know in advance.

Should a side effect appear,the physician can intervene and change the dose or change the medicine or adjust things so that we don't get severe side effects.

Patients need to know what are the potential side effects so they have an idea what to look for when they are taking a new medication.

It just goes back again to the importance of taking control of your illness and your management of your illness as well as good communication with your physician. Sometimes rheumatologists are puzzled as to why a side effect had occurred.

It's extremely important to,just pay attention to what are some of the possibilities. When you start to notice something, don't be afraid. As soon as you think something's going that shouldn't be occurring, contact your physician right away.

We need to read the brochures about the medicines, know what some of the side effects are. Sometimes it's how you're taking it, when you're taking it, with what other medications you're taking.

It's also critical that the primary care physician works with the rheumatologist and doctors talking to one another in addition to talking to the patient.

People are very worried about the new warnings concerning Arava, Enbrel, and Remicade including some deaths and instances of MS symptoms and TB. Are some people more susceptible to these complications than others?

As many people may be aware, there was recently a petition to ask the FDA to look at the potential for liver complications from Arava or leflunomide.

The FDA have addressed the issue,in question. There's a tendency when these get reported by the news media, perhaps who themselves have not seen the data, to perhaps raise an alarm that doesn't exist.

Tuberculosis is an infection you never really get rid of. Your body just effectively walls it off, and these macrophages are very important in sort of walling that off.

Anyone who's considering going on a TNF inhibitor like Remicade or Enbrel, they need to be checked for a skin test for tuberculosis.

If the skin test is negative, odds are there's really no increased risk, there are situations where that's not true, but generally speaking, and there probably isn't any substantial increased risk.

However, if you have been exposed to tuberculosis in the past, then that would mean a swelling would occur where you got the skin test for tuberculosis, then you need a chest x-ray from the doctor, and to make sure there isn't active lung involvement right now.

Depending on a person's age, the rheumatologist might say, "Well, we're just going to follow this." In the whole situation, they might say, "Yes, we can use a medicine like Enbrel or Remicade, but follow it closely with regular chest x-rays," or they might even consider putting you on medicine to prevent tuberculosis coming back.

There are a number of factors that fit into this -- one is if you're on high doses of steroids because being on more than 10 milligrams of prednisone for sure, that increases the risk of waking up tuberculosis. There are a couple different factors of that.

Now the second is a question about MS, and it comes down to the idea that rare events can occur in populations, and it's like birth defects. We don't really know how often MS really occurs in people with rheumatoid arthritis.

We know that people with rheumatoid arthritis get more lymphomas - that's a kind of lymph node cancer - than the general population, but we don't really know exactly how often MS occurs. Maybe it occurs more frequently or not as frequently.

The other answer is in on multiple sclerosis and any of these TNF inhibitors, but scietists feel strongly that if a person had MS in the past,they should not be treated with these medicines, and if people have new or strange symptoms that worry them, they should be talking with their doctor, and these are questions that most of the time can be pretty easily addressed.

Another issue is that.anyone who's using alternative therapies, particularly if these are therapies that are ingested, whether these are herbs or nutriceuticals or whatever one is using, it's really important that the doctor know about this for a couple reasons.

One, the therapy may actually be working, and the doctor is giving credit to something else. That's one thing. More importantly, there's always the possibility that the therapy could in some way potentially be interacting with what the doctor is giving the patient,it's very important that there's an open dialogue as to things that people are doing.

Alternative therapies can range from things like acupuncture, ways of exercise, biobehavioral therapies, and everybody, including rheumatologists, believe that some of these things are probably terribly important. They've not been well studied, so when we say, "Take control," some of the alternative therapies are probably the patient's best way of personally taking control, and therefore,health-care professionals would encourage people,to open up with their doctor. Have a dialogue about this.