Immune System

The immune system is the body's defense system. It works on three different levels. The first level is the anatomic response. It consists of anatomical barriers to foreign particles and includes the skin and acid in the stomach. Anatomic barriers prevent foreign substances from entering the body. If foreign particles pass through the first line of defense the second line of defense called the inflammatory response kicks in. The third line of defense is the immune response. It is the main player in specific immune defense.

The cells of the immune system mount the immune response. These cells are also called white blood cells.

There are several types: The neutrophils are responsible for killing bacteria and yeast and are the first white blood cells at the site of an infection. The eosinophils play a part in delayed reactions to foreigners. The key players of immune system are the monocytes and the lymphocytes. Monocytes are scavangers. They scour the body for anything out of place. They can engulf foreign particles and chew off pieces of tumor cells. Lymphocytes are not able to engulf any foreign particles or eat tumor cells. They take the information given to them by monocytes and monocyte-like cells and do their job. There are several types of lymphocytes. The most important types are the B lymphocytes, and the T lymphocytes. The B lymphocytes get their characteristics after being nurtured in the bone marrow, hence the B. B lymphocytes are primarily responsible for producing antibodies. Antibodies can inactive bacteria, fungi, and viruses and make them and other foreign particles easier to see by the rest of the immune system. T lymphocytes mature in the thymus gland, hence the T. For the purposes of this topic they can be divided into three major categories: the T helper cells, the T suppressor cells, and the cytotoxic T cells. The T helper and suppressor cells do exactly what their names imply. The cytotoxic T cells are primarily responsible for killing virally infected, and tumor cells.

Immune System and Cancer

In order for cancer to occur, the immune system must have failed. The normal sequence of events when the immune system comes across tumor cells follows.

An immune cell called the macrophage (also called a monocyte) comes into contact with a cancerous or precancerous cell. This cell has some strange surface features. The strange features signal the macrophage that the cell is not healthy and that the macrophage should take a bite out of it.

There are two possible scenarios that can happen next. The macrophage can either hand off these little pieces of tumor cell to another type of immune cell, or it can transform itself into another, specialized immune cell called a dendritic cell. The latter happens most often.

The macrophage then begins to digest the bite of the tumor cell. Several little packets of enzymes act like a cellular stomach and break down the piece into smaller and smaller pieces

Dendritic cells are found in all tissues of the body, and many of them began as macrophages.

Now that the macrophage has digested pieces of the tumor cell, it transforms into the dendritic cell. The dendritic cell is a much more effective messenger. When it is fully mature, it gives the information about the tumor contained in the small digested packets to the rest of the immune system. A key point here is that the dendritic cell must be mature to effectively present the tumor information. The cell needs to have additional markers on its surface that the other immune cells can recognize. These markers are called co-stimulatory molecules and are shown as white crosses on the picture of the mature dendritic cell below.

When the dendritic cell begins to mature, it also starts moving, or migrating toward a lymph node. The lymph nodes contain large numbers of lymphocytes, another type of immune cell. The lymph nodes are where the action is when it comes to the immune system.

So the mature dendritic cell has migrated to the lymph node. There it comes in contact with different kinds of lymphocytes. If it has matured properly, the co-stimulatory molecules on its surface will help pass the tumor information along to the cytotoxic T lymphocytes, or CTLs. The CTLs are the body's main defense against tumor cells. When the right CTL comes in contact with the dendritic cell, it will become activated and begin to divide, effectively making an army of cloned soldiers ready to kill any cancerous or pre-cancerous cell having the same altered membrane discovered by the macrophage.

When the CTL soldiers come in contact with cells that have the same surface as the original cancerous cell, they bind to it. They then release a chemical that pokes tiny holes in the membrane of the tumor cell, and the tumor cell spills its guts and dies.

Let's summarize what happens normally in the body after a normal cell turns cancerous. First, a macrophage comes in contact with the tumor cell, which has a different type of membrane that signals the macrophage to eat part of it. The macrophage then digests the eaten tumor cell fragment and starts to turn into a dendritic cell. It then begins to mature, and travels to a nearby lymph node and hands off the tumor cell information to CTLs. The CTLs then divide, circulate throughout the body, and kill any tumor cells they come in contact with.

This is what happens normally in the body when a cell becomes cancerous. This process occurs countless times as cells get genetic mutations and become cancerous. But, if you have cancer, then something must have gone wrong. Did the macrophage fail to recognize the funny cell surface? Did macrophages not become dendritic cells? Or did the T cells not do their job? It is impossible to tell for sure but there are some clues that the problem is with the dendritic cells.

Dendritic cells in and around tumors are present but they are immature. They don't have the co-stimulatory molecules necessary for the successful hand off of the tumor cell membrane information to the T cells. Moreover, because they are immature, they are much less likely to migrate to the lymph nodes to make the hand off.

To make a football analogy, the dendritic cell is the quarterback and needs to hand off the football to the running back (the T cell). In order to do that, he needs to move toward the running back and hand him the ball without fumbling. When the dendritic cell is immature, it just stands in one place and drops the ball. If that continues to happen, your team never scores and ultimately loses the game.

If you cut up a piece of tumor from kidney cancer or renal cell carcinoma and look at it under the microscope, you'll find millions of dendritic cells many more than in any other type of tumor. Expectedly, the majority of these dendritic cells are immature they don't have co-stimulatory molecules on them. Kidney cancer is the most likely type of cancer to disappear without a trace without any treatment, or spontaneously remiss. Apparently when someone has a spontaneous remission is the conditions in and around the tumor change enough to allow at least some of the dendritic cells to mature. This is more likely to induce a remission in renal cell carcinoma simply because of the larger numbers of dendritic cells.

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