Skin Cancer

EXPLAINING THE IMMUNE SYSTEM

Your body is constantly threatened by harmful microorganisms, such as bacteria, viruses, fungi and parasites. To keep you healthy, your immune system works steadily behind the scenes to protect you from these organisms. This protection is known as immunity, and two main types protect the body in different ways: innate (natural) and adaptive (acquired).

People are born with natural immunity, which includes physical barriers to the internal body parts and offers several defenses against harmful microorganisms. The first defense is your skin, followed by your nostrils, saliva and mucus that coats the inner linings of organs, eyes and mouth. These defenses help block microorganisms from entering the body. Although babies are born with some white blood cells that will eventually increase, their immune systems are still immature at birth. They receive a boost from their mother’s placenta and milk until their immune systems can mature.

The acquired immune system is built up over time through exposure to germs in the environment. It can adapt to new germs and remember them.

Even though we have these two types of immunity, germs sometimes get past these defenses and cause illness. When you skin your elbow, for example, the barrier is broken and harmful substances can easily enter the body (see Figure 1). Immediately after the injury, immune cells in the injured tissue begin to respond. They 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. The immune cells can recognize bacteria or foreign substances as dangerous and begin to destroy them with a general attack. This is called an immune response.

Key Components of 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 non-self, or foreign, to the body, it begins a series of reactions to identify, target and eliminate the non-self cells.

The driver of the immune system is the lymphatic system. It contains many key components.

Lymph is clear fluid circulated through lymph nodes located throughout the body, with larger concentrations near the chest, abdomen, groin, pelvis, underarms and neck. 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. Lymph moves to the lymph node, where the foreign objects, such as bacteria, viruses, toxins and chemicals, also known as antigens, are eliminated. You may notice swollen lymph nodes in your neck, for example, when you have a cold or sore throat. Those lymph nodes swell as they work to rid your body of infection. Once the immune system detects antigens, it begins to produce antibodies. Each antibody can bind to only one specific antigen, which helps destroy it. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy antigens.

Lymphocytes (white blood cells) are a significant part of the immune system. They develop in the bone marrow from lymphoblasts (immature cells found in bone marrow). Lymphoblasts mature into infection-fighting cells called 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. B-cells 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 have been attacked previously so it can recognize them more quickly if they return.

T-cells travel to the thymus to mature into helper T-cells, killer T-cells, regulatory T-cells or memory T-cells. They are especially effective at eliminating viruses and cancer cells, and each type takes on a different role in the immune system.

  • Helper T-cells identify non-self antigens and tell other immune system cells to coordinate with the B-cells for an attack.
  • Killer T-cells directly attack and destroy infected or cancer cells by releasing a protein that causes targeted cells 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, and they inhibit T-cells that attack normal, healthy cells that weren’t eliminated before leaving the thymus. These cells can also inhibit immune responses in body tissues.
  • Memory T-cells recognize and respond to previously encountered non-self antigens, and do so very quickly. Memory T-cells stay alive in your blood for years, continuing to fight the same invading cells. Memory is the basis of immune protection against disease in general and explains why we don’t usually become infected with some diseases, such as measles or chicken pox, more than once.

How Cells “Talk” to Each Other

Each part of the immune system plays an individual role in defending the body. But like any good team, these parts must be able to signal each other and communicate messages so the system can work together to respond quickly to threats. Most cells communicate by sending chemical signals. The others respond to physical stimuli, such as sensory cells on your skin or cells in your ear that react to sound waves.

To understand how cells communicate, it’s important to know that the surface of each cell is not completely round and smooth. Cells are covered with receptors and proteins, which work like puzzle pieces. Proteins have “tabs” that stick out, and receptors have “spaces” that curve inward. When the puzzle pieces fit together (known as binding), chemical signals and information are exchanged in a biochemical reaction.

Once a cell receives a signal, it reacts by sending its own chemical signals to communicate or coordinate with other cells. Cells can amplify a signal so it can travel to distant areas of the body. For example, hormone cells in the brain must travel and communicate with cells in the ovaries to release an egg.

Not all cells contain the same receptors, but they can have multiple receptors for specific proteins. Some receptors even exist within a cell and bind only with molecules that can pass through the cell’s outer membrane.

Harnessing the Power of the Immune System

Doctors realized the amazing power of the immune system years ago and wanted to harness it to fight cancer. In the 1950s, some researchers thought that in addition to protecting the body against bacteria and viruses, the immune system looked for abnormal cells and killed them before they could become tumors. This theory, called cancer immunosurveillance, was initially rejected, but it has become the foundation upon which immunotherapy was built.

Although tumors may develop in spite of a functioning immune system, the way a tumor grows and develops is influenced by the body’s immune response. Based on this evidence, and confirmed by studies conducted by cancer researcher Dr. Robert Schreiber, the theory was renamed “cancer immuno-editing.” Dr. Schreiber’s theory of cancer immunoediting is composed of the Three Es:

  1. Elimination. The immune system sees and destroys cancer cells. In this phase, our bodies may be regularly introduced to cancerous changes, and our immune systems are capable of handling and eliminating them.
  2. Equilibrium. If the cancer cells are not destroyed right away, they may exist in a delicate balance between growth and control by the immune system. During equilibrium, the body’s immune system is able to keep the cancer cells in check but unable to kill them completely. In this phase, a tumor may remain dormant for an unknown length of time and evade medical testing. According to the theory, however, the constant interactions between the tumor cells and immune system cells may lead to tumors that can adapt to the immune response. This means the immune system may no longer be able to recognize tumors and attack them. Tumors that avoid the immune response can no longer be controlled and move on to the third phase.
  3. Escape. The escape phase refers to the disruption of equilibrium, which allows tumors to escape and begin growing in an environment of immune “tolerance.” It’s at this point that the symptoms of cancer begin to appear. Tumors in the escape phase can grow by using a number of methods to alter the body’s immune response.

The Immune System vs. Cancer

The immune system uses the same process to recognize and eliminate cancer as it does to remove other non-self cells. But the process is more complicated because cancer cells are created by the body, so the normal ways to find and fight invading cells from outside the body aren’t always effective.

The normal process for an immune response begins when B-cells and helper T-cells identify the threat and tell the rest of the immune system. The body then ramps up its production of T-cells to fight. Killer T-cells are sent to destroy the non-self cells. To prevent the T-cells from attacking healthy parts of the body, regulatory T-cells are sent to slow the immune system down once the non-self cells have been eliminated. As a result, the body slows production of T-cells, which then return to normal levels.

Cancer develops when one or several abnormal cells divide and multiply to become a mass (tumor). The tumor may become different enough from the body that the immune system recognizes it as non-self and stimulates an immune response. However, the immune system may have difficulty identifying cancer cells as non-self. It may still see them as part of the body and not coordinate an attack. If the body can’t tell the difference between tumor cells and normal cells, the tumor cells may be able to “hide” and evade the immune system (see How Cancer Hides from the Immune System).

The longer the cancer cells face a weakened immune response, the more they’re able to adapt, and the easier it is for them to manipulate immune cells inside the tumor’s location, sometimes called the microenvironment area.

Immunotherapy offers the immune system reinforcements to keep up its fight, whether that is through taking the brakes off the system, boosting it with modified T-cells or combining it with chemotherapy or radiation therapy (see Exploring Immunotherapy).

 

Illustration: Figure 1 Normal Immune Response (filename: Explaining Fig 1)

Illustration: How cancer hides from the immune system (filename: Explaining Policeman)

 

SIDEBAR: EXPANDING THE IMMUNE SYSTEM'S MEMORY

Although cancer cells can be clever, the immune system has a long memory when it comes to battling dangerous cells. When your immune system encounters a virus, such as chicken pox, the memory T-cells check to see if that virus has any characteristics of cells they have attacked in the past. If so, your memory T-cells offer you immunity from that virus, and most of the time, you don’t get the chicken pox again. The memory T-cells alert the rest of the immune system and tell it to make more immune cells to attack the virus and keep you from getting the disease again. Memory T-cells stay alive and store this information for a long time, remaining effective long after treatment ends. Investigators believe that effective immunotherapy can result in cancer-specific memory cells that provide long-term protection against cancer.