T-Cells: The Dark Side
What we thought was cancer’s worst enemy can actually become the brain’s biggest threat.
My grandfather was diagnosed with bladder cancer when I was only a few years old. He suffered throughout his late sixties and is still recovering today. His treatment involved many chemotherapy sessions, but doctors have been suggesting for him to try other therapies — therapies involving T-cells.
T-cells are responsible for terminating cancerous cells in our bodies. There are even immunotherapies that involve engineering T-cells from patients’ blood samples and optimizing their cancer-terminating capabilities (CAR-T cell therapy).
Cancer emerges when unregulated mitosis becomes uncontrollable. This results in rapid cell division of abnormal, mutated cells.
When T-cells become uncontrollable, autoimmune diseases emerge. This results in autoimmune diseases we know as HIV, rheumatoid arthritis, and multiple sclerosis. Before I dive into the dark side of T-cells, let’s begin with how the immune system is supposed to operate — beginning with the lymphatic system.
The Lymphatic System
Everyone knows the purpose of wearing face masks. Attackers (viruses, microorganisms, bacteria) can get into the body through our mouth or nose by traveling alongside the air particles we constantly inhale.
These invaders can then travel throughout the body with the help of the circulatory system and lymphatic system.
The lymphatic system is a secondary transport system that is separate from standard blood circulation and produces and transports B and T-cells. It is made up of an array of lymph vessels and lymph nodes.
Lymphs containing white blood cells or disease-causing toxins in the lymphatic system do not get pushed around like nutrients or red blood cells being circulated throughout the circulatory system. The lymphatic system is not pumped by the heart. Instead, the lymphs move through the contraction of neighboring muscles. Here’s a better way to understand it:
When you turn your garden hose off, the water obviously stops moving out of the hose. If you step on the hose with your foot, you’re forcing the remaining water in the tube to move in a certain direction, whether it is towards the main water tank or outside the hose.
Your foot stepping on the hose acts as the contraction of neighboring muscle groups. The lymphs of the lymphatic system is represented by the water left in the hose. Lymphs play key roles in the body’s vast immune system.
The Immune System
In order for a foreign attack to be successful, they must evade or overcome the immune system which divided into three main lines of defense.
The first line of defense
The skin and mucus membranes make up the first line of defense. At this level, an immune response is classified as non-specific (or does not have a fixated defense against a specific pathogen).
The second line of defense
NK (natural killer) cells and antimicrobial proteins make up the second line of defense. NK cells are known to kill virus- and cancer-infected cells, while antimicrobial proteins are known to attack bacteria and fungal cells by drilling holes into their cell membranes.
Inflammatory responses occur at this level of attack. You may notice that inflammation of the skin is hot-to-the-touch because the temperature of infected tissue must be able to denature pathogenic enzymes and proteins.
In addition to a rise in temperature, capillaries dilate and white blood cells, red blood cells, and platelets are delivered to the infected site to fight off attackers and form blood clots.
The third line of defense
B-cells, T-cells, and antibodies make up the third line of defense. Antibodies are proteins that bind to a specific antigen (or a protein on a pathogen). They are similar to handcuffs because when an antibody clamps onto its complementary antigen, the antigen can no longer trigger immune responses and affect neighboring tissue. Once an antigen is secured, free-floating antibodies are then engulfed by macrophages via endocytosis to be sliced up and reused for other bodily needs.
The common responsibility among B- and T-cells is to recognize foreign particles in order to individually attack them and trigger the rest of the body to follow suit.
The role of B-cells is to recognize antigens of the pathogens and produce what is called a humoral response, only attacking foreigners circulating in the blood or lymphs in order produce antibodies for antigens expressed by the circulating, infected cells.
When a pathogen slips past the B-cells or has reproduced so much to the point where they outnumber B-cells, T-cells come to the rescue. The main duty of T-cells is to recognize antigens of the infected cells.
Helper-T-cells (Th-cells) alert other T-cells to kill off invaders and alert B-cells to make antibodies (acting as a general of an army). Cytotoxic (killer) T-cells attack infected cells upon command (acting as the soldiers of the army).
Th-cells can tell which cells are infected because MHC or major histocompatibility proteins present antigens on the surface of cell membranes in order to flag themselves as infected. Specific TCRs (T-cell receptors) bind to the presented antigens and trigger a cascade of alarms within the body. These alarms are called cytokines or special chemical signals secreted by Th-cells to alert other white blood cells.
But what happens when Th-cells and killer T-cells do not do their jobs properly?
The Dark Side: Multiple Sclerosis
Any autoimmune disease involves the body targeting its own healthy cells. According to a 2014 study conducted by the Department of Immunology and Translational Research of Canberra Hospital in Australia, women get autoimmune diseases at a rate of about 2 to 1 compared to men — 6.4 % of women vs. 2.7% of men. The disease often begins during a woman’s childbearing years (ages 15 to 44).
The substantial causes of autoimmune diseases are still unknown.
A common theory called the hygiene hypothesis states that children and young adults are not as exposed to as many germs as they were in the past — because nowadays, vaccines and antibiotics exist — therefore, their immune systems are not as prepared to battle so many different pathogens from the external environment.
There is another hypothesis that suggests that autoimmune diseases are linked to eating a Western diet (high in sugar and fat) resulting in inflammation, the first stage of numerous autoimmune diseases.
We also must not forget carcinogens and mutagens such as tobacco, UV radiation, and asbestos that can possibly contribute to the development of such diseases.
Certain autoimmune diseases such as multiple sclerosis and lupus are genetic and run in families. Not every family member will have the disease, but they inherit a susceptibility to an autoimmune condition.
An autoimmune disease I have been currently studying is multiple sclerosis (MS). I’ve been focusing on how it is linked to T-cells invading the blood-brain barrier.
MS damages the myelin sheath, the protective coating surrounding nerve cells within the central nervous system (CNS). Damage to the myelin sheath slows the transmission speed of messages between the brain and spinal cord to and from the rest of the body.
This damage can lead to symptoms such as numbness, weakness, balance issues, and immobility. The disease comes in several forms that progress at different rates.
According to a 2012 review of MS conducted by Dr. Marvin Goldenberg, about 50% of people with MS need help walking within 15 years of the disease starts.
*Note: Th# is an abbreviation for a type of T-helper-cell
These cells wreak havoc in the CNS by releasing a special class of cytokines specific to white blood cells called interleukins to invade the selectively-permeable blood-brain barrier.
The sole purpose of the blood-brain barrier is to guard the CNS from toxins and combative white blood cells. The study has shown that T-cells are not the only culprit for causing MS.
In the initial relapsing–remitting phase of MS, CD4+ T-cells, CD8+ T-cells, B-cells, and macrophages migrate across the blood–brain barrier to disrupt the structures of microglia and myelin sheaths protecting neurons.
To understand the function of the blood-brain barrier and its cellular components in greater detail, please check out this article.
There are nonpathogenic and pathogenic T-cell subtypes. Th17 is a subtype that can have both qualities.
Nonpathogenic (non-disease-causing) Th17 cells secrete IL-9 and IL-10, while pathogenic Th17 cells secrete IL-17, IFN‐γ (interferon gamma), GM-CSF (granulocyte-macrophage colony stimulating factor), IL-22, and even IL-12.
*Note: IL-# is an abbreviation for interleukin-#
IL-12 is the most dangerous of interleukins in MS cases. IL-12 activates platelets or the “blood-clotters” of the body to trigger an enhanced inflammatory response to myelin sheathes.
As mentioned above, T-cells typically attack abnormal cells due to their recognition of antigens. In T-cell-related MS, this is not the case.
One hypothesis suggests that CD80 and CD86, proteins that lie on the surface of T-helper-cells, is linked to brain inflammatory lesions, such as active stroke lesions and MS plaques.
Before the world can be presented with a cure for autoimmune diseases like MS, research must debunk the many mysteries that lie within the immune system. Immunologists should especially uncover what I nicknamed the dark side of T-cells.
Thank you for reaching the end of my article.
Who knew T-cells, the body’s greatest warriors, had an evil, mysterious side?
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