Monday, July 03, 2006

Time For Another Science Lesson

When we went to Clinic on Friday we were told that Parker had started making his own IgM. Ig stands for immunoglobulin and the M is a specific type of immunoglobulin. Parker receives IgG every six weeks or so to help his immune system. We are not sure if Parker has created his own IgG yet, since his complete blood count (CBC) shows that it decreases in numbers from week to week. Last week, it decreased less than it normally does, so there is the possibility that he may be creating his own IgG as well. We will not know this for sure until we go to clinic and they say that it is up from the previous week. If it is not up at his next CBC then he will get another high dose of IgG though an IV. I have been meaning to write a more educational article for a while, so I thought that this would be the perfect time.

Now, I know that most of what I talk about in my articles are about Parker's lymphocytes but these are only one portion of his immune system. That said, they are a very big portion of his immune system. But today, I thought I would I explain how the lymphocytes work with the rest of his immune system to fight infections.

I shall begin by just reviewing a few terms that I most likely have mentioned in previous articles. I hope this makes the rest of the article a little easier to understand. Parker's disease has caused his body to be void of lymphocytes. Lymphocytes are composed of three types of cells, T-cells, B-cells, and Natural Killer (NK) cells. To further differentiate between these types of cells, the T-cells can be divided into three different types of T-lymphocytes. These being cytotoxic T-cells, Helper T-cells and Regulatory T-cells.

Below is a T-cell fighting a tumor cell.

The three types of T-cells are identified by the type of receptor they contain. Tc are incharge of destroying infected cells and contain the receptor CD8. TH are called helper T-cells and aid the rest of the immune system in fighting infection and contains the receptor CD4. This can be seen later in the article when I talk about how it works with the macrophages and the B-cells to produce antibodies to fight infection. Finally, regulatory T-cells aid in the supression of the immune system. These T-cells contain two receptors (surface proteins), CD4 and CD25. The receptors allow for specific cells to bind to them. The purpose of the Natural Killer cells are to contain viruses while the cytotoxic T-cells can clear the infection.

I have spent quite a bit of time in previous articles writing about the T-lymphocytes, but now I would like to talk abit about how the B-lymphocytes take part in an immune response. This is also where we will look at what an immunoglobulin really is.

There are usually millions of B-cells that circulate through the body at any given time. Once a B-cell encouters a particular antigen (something that produces an immune response - something foreign to the body), and a signal from a Helper T-cell it turns into one of two types of B-cells. The first is a Plasma B cell and the second is a Memory B-cell. Once a new antigen enters the body and comes in contact with a B cell, the B cell creates plasma cells. The purpose of the plasma cell is to create antibodies (immunoglobulins) that the antigens may bind to. Once bound, it becomes easier for specific cells called phagocytes to engulf the bad antigen. Memory B-cells are created for specific antigens and are meant for fighting antigens that the body has previously seen before. This is why when you catch something that is caused by something you have previously had your body already has cells that have seen it and are ready to fight. This allows you to get rid of what ever you have caught more readily. But what about the flu? See, the flu changes all the time and for that reason when the flu virus enters your body the following year it does so with a different shape. The Memory B-cells do not have the receptors that allow it to bind to the newly modified antigens of the flu virus. Thus, the B-cells must create new plasma cells that may in turn create an antibody with receptors that will allow it to bind.

Let's take a closer look at the antibody that the plasma cells create. I just mentioned that the word antibody can be used interchangably with immunoglobulins. So, when I talk about Parker's IgG and IgM I am talking about his antibodies.

An immunoglobulin (Ig) is a protein that is shaped like the letter Y. Each antibody is made of two Heavy Chains and two Light Chains. Think of the chains as a bunch of molecules linked together. At the two top ends of the Y, are located recepters, where the antigens may bind to. Once bound, it is an easy target for the phagocytes. I do not want to go to indepth with the different heavy and light chains, but I will say that there are five heavy chains. Depending on which type of heavy chain the antibody is made of will define the type of immunoglobulin. Therefore, there are five types of immunoglobulins. They are IgG, IgM, IgA, IgE, and IgD. The smallest of the immunoglobulins and the most prevelent in the body are the IgG. These are the only type that are smallest enough to pass through the placenta of a childs mother. For that reason, this is the only type of immunoglobulin that an infant has at birth. To be honest, I am not sure how many Parker had when he was born because the toxins in his body would have destroyed them quite quickly. A normal infant would be able to have them to fight off pathogens while there body was still learning how to make IgG. As I previously mentioned, I think Parker may actually be creating his own IgG now.

IgM are immunoglobulins in which five different immunoglobulins are bound together in the shape of a pentagon. By having five immunoglobulins there are ten binding sites for antigens and therefore has greater flexibility when performing an immune response. That said, we have all heard the saying that it is better to do one thing extremely well, then to do alot of things mediocre. IgG has a high affinity meaning it has a high binding strength of the antibody to the antigen. IgM has a high avidity meaning it has a high number of binding sites. IgM remains in the bloodstream where it can kill bacteria that enter the blood stream. IgG has the ability to enter tisse. It can coat the pathogens, helping other cells to seek and destroy them.

The purpose of IgE is to help the body with allergic reactions. When an allergen is ingested, inhaled or absorbed through the skin, it stimulates the production of an antibody called immunoglobulin E, or IgE.

The role of the other two types of immunoglobulins are not that well defined and for that reason I have decided to omit them here.

The lymphocytes are part of a broad form of cell called the white blood cells. The white blood cells consist of the three types of cells called lymphocytes, monocytes, and granulocytes. Now, I have already reviewed the different types of lymphocytes, but the granulocytes can also be broken down into different forms of cells.

Granulocytes consist of neutrophils, basophils, and eosinophils. At one time Parker's neutrophil count was quite low (neutropenic) as a result of what we believe to be a medication he was on at the time. I have covered neutrophils in another article but I will refresh everyone with what its purpose is. Neutrophils fight bacterial infections by engulfing bacterium. Any form of cell that injests and destroys cells are refered to as phagoctyes and neutrophils are one form of phagocyte. Here is a link to a neutrophil seeking out a bacterium as it tries to rid it from the body. Whenever a large number of neutrophils are working and die they form pus. Basophils are responsible for releasing histamine whenever you have an allergic reaction. This causes inflammation. The eosiniphils main funtion is to fight infections in the body caused by parasites. Although, I have mentioned eosiniphils and basophils, with Parker our main concern are the neutrophils since he was neutropenic at one time.

Monocytes are another form of phagocyte (cell that engulf -"vacuum cleaner' - other cells) similar to the neutrophils. Monocytes are also known as macrophages, which I will refer to them as from now on. There are many places that you can find macrophages, they begin in the blood stream but can migrate to other tissue. The problem that Parker had with his lungs when we first entered the hospital (Pulmonary Alveolar Proteinosis - PAP) can be repaired by stimulating macrophages. PAP is caused by protein that has accumulated in the lung tissue. In a sense it causes it to become "dirty". By stimulating the production of alveloar macrophages the proteinosis can be repaired. Currently, Parker's proteinosis is not active. It is the reason that we brought Parker to the hospital originally as the need for oxygen, rapid breathing and loss of appetite that it caused mirrored the symptoms of many infections that may take place in the lungs. We are unsure why it is not active, as we never treated it. The intent was to stimulate macrophage production with a drug called GM-CSF (Granuloyte Macrophage Colony-Stimulating Factor). It is a protein secreted my macrophages that stimulates stem cells to produce granulocytes and macrophages.

Macrophages are similar to neutrophils but they do have some differences in function. First they last longer in the system than do neutrophils, but they also work with the Helper T-cell so that an antibody response may be activated. On the left is a monocyte and on the right are two neutrophils.

Here is an image from an electron microscope of a T-cell riding along a macrophages that has come in contact with a bacteria.

When the macrophage eats bacteria, antigens from the bacteria are then broken down and displayed on the macrophage. If that T-cell that is riding along with the macrophage sees a B-cell with the same antigen it tells the B-cell to create antibodies so that it may help fight infections. The antibodies bind to the bacteria allowing them to be more easily injested by the white blood cells. This can be illustrated below.

I know that is quite a bit of information for everyone to digest, like a phagocyte, but I have been looking forward to writing an article like this for a while. I hope that it helps a few people understand what is going on in their body. Let's just hope that Parker continues to produce the different immunoglobulins, that the three different types of T-cells start to increase, and he does not become neutropenic again.

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