A Fascinating Behind-the-Scenes Look at Your Immune System

Immunotherapy is a process that uses your body’s immune system to fight cancer. To better understand how immunotherapy works, let’s get into detail about how your immune system works.

Lymphocytes, T-cells, and B-cells

Your body has immune cells that do this by recognizing specific targets on the surface of the pathogen, a bacterium, virus, or other microorganisms or cancer cell that can cause disease. These cells are called Lymphocytes, which are a special kind of white blood cell.

There are two main types of lymphocytes, B-cells and T-cells. T cells and B cells are major cellular components of the adaptive immune response.

T Cells

The “T” in T cells relates to the fact that these cells come from the thymus, a specialized organ of the immune system. While all of your white blood cells are made in the bone marrow, T cells are a special subset of white blood cells that start in the bone marrow and then migrate to the thymus.

The thymus cells convert the T cells into specialized (CD8+ or CD4+) T-lymphocytes to tell the difference between your cells and pathogens.

T cells are involved in cell-mediated immunity, an immune response involving T cells (T Lymphocytes) that do not involve antibodies. There are four main types of T cells:

  1. Cytotoxic T cells (CD8+) – have a co-receptor called CD8 that allows them to recognize normal cells infected by a pathogen and produces molecules that kill the infected cell and the pathogen.
  2. Helper T cells (CD4+) (Th cells) – have a different co-receptor called CD4 that partners with the T cell receptor to produce molecules called cytokines that signal to other immune cells.
  3. 3. Regulatory T cells (Treg cells) – also have CD4 on their surface but do not activate the immune system as helper T cells do. Instead, they shut off the immune response when it is no longer needed.
  4. Natural killer T (NKT) cells – respond to tumor cells and contribute to anti-tumor immune responses. NKT cells need to be pre-activated and differentiated to work.

Cell-mediated immunity – the activation of:

  • Phagocytes – A cell that engulfs and absorbs bacteria and other small cells and particles.
  • Antigen-specific cytotoxic T-lymphocytes (CTL) – T cells that kill cancer cells, infected cells (particularly with viruses), or cells damaged in other ways.
  • The release of various cytokines – small proteins essential in cell signaling.

B cells

B cells originate from stem cells in the bone marrow and migrate to the lymph nodes. Or B cells come from bursa-derived cells. The bursa is a membrane that acts as a cushion between the muscle and bone.

In contrast to the T cells, B cells are primarily responsible for humoral immunity. (humoral – relating to body fluids)

Humoral immunity – is the release of antigen-specific antibodies. An antigen is a molecule that stimulates an immune response by activating lymphocytes. Antibodies, also called immunoglobulins, are a Y-shaped blood protein that combines chemically with antigens to fight pathogens.

Every so often, B-cells and T-cells will work together in the battle against your body’s invaders.

Two types of immunity: active and passive

There are two types of immunity: active and passive. Let’s try and make this distinction clear.

When a pathogen invades your body, lymphocytes produce antibodies that can kill the pathogen. There are many types of lymphocytes producing unique antibodies. The problem is, each pathogen needs an exact antibody to terminate it.

Because there are so many lymphocyte types, it takes your body some time to decide which one will destroy a specific pathogen. During this time, the pathogen keeps reproducing, causing all sorts of cellular damage and makes you sick. Eventually, your immune system finds the right lymphocyte it needs, and two things will happen.

First, T cells are produced that create antibodies destroying the pathogen, and you get better again. The next thing that happens is at the end of each battle to kill the pathogen, some T-cells and B-cells turn into Memory T-cells and Memory B-cells. These stay in your body and will recognize that pathogen if it comes back.

If the pathogen comes back to your body six months or a few years later, the memory cell will immediately recognize it and produce the cells that produce the antibodies. Quickly the pathogen will be destroyed before you can get sick. Because the memory cells are active within your body, we call it active immunity.

Active immunity is the resistance to pathogens acquired during an adaptive immune response. Before there are memory cells, the immune response coming from the lymphocyte is passive immunity. Not too hard to understand.

CAR T cell therapy

Now that you have learned about lymphocytes, the different types, T cells and B cells, and their various functions, let’s see how it relates to cancer and immunotherapy.

If your immune system is working correctly, it wants to kill cancer cells.  That’s its job, create T cells that patrol your body and protect you from diseases. The T cells inspect suspicious cells and when they find an abnormal one and immediately lead an attack on it while limiting the damage to healthy cells.

The way they do that is T cells have protein receptors on their surface. These claw-like structures latch onto the antigens. When a receptor latches onto a pathogen’s abnormal antigen, the T cell turns on and releases cytotoxic chemicals that damage the abnormal cell. Then it recruits the Helper T cells (CD4+), releasing cytokines to signal other immune cells.

Sometimes cancer cells develop ways to fool your immune system either by:

  • Disguising themselves as healthy cells.
  • Sprouting so many antigens, T cells are thwarted and can’t launch an effective attack.
  • Finding a way to turn off the immune response against them.

One innovative way to see through the deception is CAR T cell therapy. Thousands of a patient’s own T cells are collected in a process similar to a blood donation. Using a modified inactive disease that can’t cause any disease but can introduce genetic information into a cell. The T cells are now reprogrammed, producing special receptors called chimeric antigen receptors, or CARs on their surface.

These newly engineered cells called CAR T cells are grown in a lab, and millions of them are infused back into the patient. The new receptors enable them to latch onto a specific antigen on the patient’s tumor cells and destroy them.

Other Immunotherapy types

Thanks to your immune system, you already have the power to fight cancer inside of you! Although the immune system is typically associated with protecting us from viruses, bacteria, and other disease-causing organisms, it has a significant role in fighting cancer by recognizing and killing cancer cells. In addition to CAR T cell therapy, there is also:

  • Monoclonal antibodies and tumor-agnostic treatments, such as checkpoint inhibitors
  • Oncolytic virus therapy
  • Cancer vaccines

If you’re interested to see if immunotherapy is a solution for you, discuss it with your doctor. They can help you create a program with an immunotherapy type that best matches your particular cancer. 

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