Immunotherapy

Explaining the Immune System

Every day our bodies encounter various organisms that could negatively affect our health. To fight against them, we all have an immune system working to identify these attackers and eliminate them, keeping us healthy.

Even though you may be unaware that your immune system is functioning, it is always working. You may notice it when an infection or irritation you can see or feel occurs. An example is when a bug bites your skin. You may develop an itchy, red bump. The bump is a physical sign that your immune system is working. Over a period of days, your immune system counteracts the reaction to the bite and heals it.

Another example is when you develop a cold. Germs can occasionally get past the defenses of the immune system through our nostrils, skin, saliva and mucus coating the inner linings of organs, eyes and mouth. When this occurs, you may experience a cold. Your immune system works to destroy the virus or bacteria that caused your illness. A working immune system helps you recover from the illness.

Understanding the Immune System

The immune system is a complex network of cells, molecules, organs and lymph tissues working together to defend the body against germs, cancer cells and other microscopic invaders. The first job of the immune system is to distinguish between what is part of the body (“self”) and what is not part of the body (“non-self”). Once the immune system determines that a cell is foreign to the body, it begins a series of reactions to identify, target and eliminate the foreign cell.

The key driver of the immune system is the lymphatic system because it circulates clear fluid called lymph through the body to accomplish several jobs:

  • Defend the body against harmful substances, such as germs
  • Fight infections
  • Drain fluids from the body’s tissues from the bloodstream to help the body maintain proper fluid levels
  • Filter lymph through the lymph nodes
  • Filter blood through the spleen
  • Identify and eliminate cancer cells

Lymph nodes, located throughout the body (with larger concentrations near the chest, abdomen, groin, pelvis, underarms and neck), circulate lymph. Although lymph and lymph nodes make up a large part of the lymphatic system, it also includes other organs, such as the skin, thymus, spleen, appendix, tonsils and adenoids. These organs collect, filter and circulate lymph. The lymph is able to contain and filter bacteria, viruses, toxins and chemicals, known as antigens, which are circulating in the lymphatic system and the bloodstream. These bacteria, viruses, toxins and chemicals are considered non-self antigens, meaning they originate outside of the body.

As the lymph passes through a lymph node, white blood cells (lymphocytes) within the node intercept the non-self antigens. Once the body recognizes these types of antigens, it produces antibodies to attack them or activates T-cells to destroy cells with these non-self antigens. When these levels increase in the body, due to an infection, more antibodies are made to fight the specific non-self antigen causing the infection.

Lymphocytes are a major part of the immune system. They begin in the bone marrow and develop from lymphoblasts (immature cells found in bone marrow). Lymphoblasts mature into infection-fighting cells. The two main types of lymphocytes are B-lymphocytes (B-cells) and T-lymphocytes (T-cells).

  • B-cells develop in the bone marrow and mature into either plasma cells or memory cells. Plasma cells make antibodies to fight germs and infection. The function of B-cells is to produce protein antibodies that attach to infectious organisms, such as bacteria and some viruses, marking them for destruction. However, they can only identify them, not destroy them. Memory cells help the body remember which antigens attacked the body so it can recognize them if they return.
  • T-cells also develop in the bone marrow but travel to the thymus to mature into helper T-cells, killer T-cells, regulatory T-cells or memory T-cells. Each type of T-cell plays a part in the immune system. Helper T-cells identify nonself antigens and tell other immune system cells to coordinate with the B-cells for an attack. Killer T-cells directly attack and destroy these cells by inserting a protein that causes them to enlarge and burst. One type of killer T-cell is cytotoxic, which means it specifically targets cancer cells. Regulatory T-cells slow down the immune system after an immune response is finished, and they inhibit T-cells that attack normal, healthy cells that did not get eliminated before leaving the thymus. Memory T-cells can stay alive for years, continuing to fight off the same invading cells. Memory is the basis of immune protection against disease in general and explains why we don’t become infected with some diseases, such as measles or chicken pox, more than once. T-cells are especially effective at eliminating viruses and cancer cells.

Another key part of the immune system is skin. Skin is the immune system’s first barrier of protection. When you skin your knee, for example, the barrier is broken and harmful substances can easily enter the body (see Figure 1). As soon as the injury occurs, immune cells in the injured tissue begin to respond and call other immune cells that have been circulating in your body to gather at the site and release messenger proteins, called cytokines, to call other immune cells to help defend the body. This process is called an immune response. The immune cells can recognize any bacteria or foreign substances as dangerous, non-self antigens and begin to destroy them with a general attack. Although this attack can kill some of the dangerous cells, it may not be able to destroy all of them or prevent them from multiplying.

                      Figure 1

How the Immune System Attacks Cancer

Our immune system basically attacks cancer the same way it attacks dangerous, non-self antigens, but the process is more complicated because cancer cells are created by the body (or “self”). If the immune system sees cancer cells as a normal part of the body, the tumor cells can effectively “hide” from the immune system.

Cancer develops when one or several abnormal cells divide and multiply to become a mass of abnormal cells (tumor). Mutations in DNA may cause normal cells to become abnormal or different enough from the body that the immune system may recognize the cancer cells as non-self, which may stimulate an immune response. But, because the cells started as normal cells, the immune system may still see the cancer cells as self antigens and not coordinate an attack.

To understand how cells in the body interact, it is important to know that the surface of cells is not completely round and smooth. Instead, it contains various proteins, sugars, fats and other molecules that stick out of the cells' surface. These components contain information that is shared between cells through chemical signals and their receptors. One of the key cells needed to stimulate an immune response is the antigen-presenting cell (APC). APCs are able to find and pick up dangerous antigens, “eat” them and prepare them to be presented to other cells by sharing the antigens on their surface to be recognized by T-cells. In this manner, the APC sounds an alarm that there is an intruder in the body, and T-cells respond to this alarm. When a T-cell encounters an APC, it changes into either a killer T-cell to fight the intruder or a helper T-cell to begin assisting or “helping” the immune response.

Cancer cells are smart. Over time, not only can they change, they can use multiple methods to escape or confuse the immune system. Cancer cells produce proteins on their surface that they use to hide from the immune system, like camouflage. In addition, cancer cells can create their own messengers (cytokines), which means that the cancer cells can communicate and confuse other immune cells, allowing the cancer to take control of certain parts of the process that the body uses to regulate the immune response. This means that even if the immune system recognizes the cancer, it may not be able to successfully start or maintain an attack long enough to kill the cancer cells.

The longer the cancer cells face a weakened immune response, the more they are able to adapt, and the easier it is for them to manipulate immune cells inside the tumor’s location (sometimes called the microenvironment). The microenvironment typically contains cancer cells, normal connective tissues that form the structure of the tumor and provide access to blood vessels that drive tumor growth, and several cell types that contribute to tumor development. Immune cells found in this area are often referred to as tumor-infiltrating lymphocytes (TILs). Because the tumor can control the cells in the area, the tumor can trick TILs into becoming useless or even helping the tumor grow.

For example, APCs in the tumor area may be confused by signals from tumor cells, preventing them from functioning properly and making them incapable of sounding the alarm about a threat. In some cases, tumors can increase the activity of regulatory T-cells inside the area. In addition, this naturally slows down the immune system after an attack is completed. By increasing the activity of regulatory T-cells, the tumor is recruiting the body’s own immune cells to fight off the attack, using the very processes that normally protect the body to help the cancer cells multiply undetected. Tumors often contain more than one type of cell and, when a tumor changes the composition of its cells, this can confuse the immune system. The longer the immune system is exposed to the tumor, the weaker the immune response becomes. Immunotherapy treatments and research focus on identifying different ways tumors manipulate the immune system and how to reverse those processes.

 

Inside the Immune System

The immune system faces a variety of challenges as it attempts to protect the body from cancer.

How Cancer Hides from the Immune System

Imagine a police officer (a T-cell) who encounters a suspicious person (a cancer cell). He asks the suspicious person for identification to determine if the suspect should be let go or arrested. If the police officer thinks the person does not pose a threat (a healthy cell), he will let him go. If he thinks he is dangerous (a cancer cell), he will call for backup (activate the immune system). However, the suspicious person may use fake identification to appear friendly with the hope that the police officer will think he is a normal, law-abiding citizen and send him on his way.

Cancer cells are clever and do the same thing by disguising themselves. The cancer cell produces proteins on its surface to alter its appearance, making it look like a normal, healthy cell to the T-cell. If the cancer cell is successful, the T-cell will be fooled and will let the cancer cell continue to attack the body.

How the Immune System Remembers

Although cancer cells can be sneaky, the immune system has a long memory when it comes to battling dangerous cells. When your immune system encounters a virus like chicken pox, the memory T-cells automatically remember if it’s exposed to it again and offers you immunity from that virus. Memory T-cells stay alive for a long time and store information about the cells the immune system attacked. When a memory T-cell interacts with a dangerous cell, it checks to see if it has any characteristics that match any of the cells it previously attacked. If it does, the memory T-cell alerts the rest of the immune system that a virus, for example, is back and to make more immune cells to attack it and keep you from getting the disease again. It offers the ability to be effective long after the treatment is ended.

With immunotherapy, one of the main goals is for the immune system to recognize cancer cells when they try to return. If the body can remember cancer and prevent it from recurring, this can lead to long-term, cancer-free remission and increased overall survival, in a way that no other therapies used to treat cancer can do.

 

Additional Resources

 

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