Étiquette : immunity

The Immune System IV

Le par julienforsciencedans Immunology / ImmunologieLaisser un commentaire
When the immune system goes wrong

Today we will finally end our epic journey towards understanding the immune system. We have covered a lot on the subject, and we know that the body is amazing at protecting itself. Unfortunately, the immune system is not prefect, and there are many ways it can go wrong. Today we will review three ways where the immune system is not behaving properly: allergies, autoimmune diseases, and immunodeficiency.

Allergies, or when the body is desperately looking for problems when there are none.

The concept of allergies is simple: the body will react too strongly to a harmless antigen. In cases of allergies, antigens are called allergens. Allergens most often come from food or pollen, but virtually anything could cause an allergic reaction. The development of allergies is similar to any inflammatory reaction: an allergen enters the body and is picked up by dendritic cells to be presented to lymphocytes. Allergens causes the CD4 T cells to develop into a Th2 response, increasing antibody production against the allergens. This time however, a very specific type of antibody, called IgE, will be produced. These IgE will bind to a special type of white blood cell called the mast cells. These cells are loaded with large vesicles containing lots of cytokines. At the end of this phase, the mast cells will have many IgE and will be ready to act the next time the allergen comes. This phase is known as the sensitization. At this point, we have developed an allergy, but we haven’t suffered from it yet. If the allergen comes back, then it will be picked up by the mast cell, which will then unload all of its cytokines, resulting in an immune attack. The problem is, there is nothing to attack. Therefore, you end up with the allergic symptoms (itchiness, sneezing, coughing, etc…) but they usually resolve when the allergen is removed. However, if there is a consistent exposure to the allergen, then more damage will occur: cell death, irritation of the lungs, and many more will occur. Lastly, for still unknown reasons, some allergies are deadly. They lead to what is called an anaphylactic shock, which is due to the massive cytokine release all over the body, leading to a very strong immune response everywhere. Whereas allergies are usually limited to one part of the body, anaphylaxis is on the entire body, making it very dangerous. The most deadly effect is the constriction of heart and lung muscles, which prevent the person from breathing correctly, and the heart may stop. The blood pressure also drops significantly. Fortunately can be stopped if we act fast. The easiest way is using an EpiPen, which injects a hormone called epinephrine (also called adrenaline), which opposes every effects of anaphylaxis: it increases blood pressure, and relaxes muscles [source / source / source / source / source].

Allergies can be very dangerous, but unfortunately we still don’t know everything about them. While we understand how they work, we do not know why certain individual develop allergies while other don’t. We however have many hypotheses, and one of them is the hygiene hypothesis. During evolution, humans have evolved to clean themselves and their environment, which drastically reduced the incidence of diseases. Unfortunately, it also reduced exposure to those diseases. Exposure is what helps the immune system understand what is dangerous and what isn’t. Nowadays, the almost too-clean environment prevents a decent exposure, which makes the body more wary to everything. While this hypothesis is not proven, it is supported by the increase in allergies nowadays. However, the hygiene hypothesis cannot be the only explanation to allergies, and many think that there is a heavy genetic component. It would explain why certain countries are more at risk to allergies than other. In the end, we still need to study allergies to better treat people that suffer from it [source / source / source].

Autoimmune diseases, or the body attacking itself

I mentioned in the article on the innate immune system how essential the self vs. non-self discrimination was. A failure to discriminate both will result in autoimmune diseases. People suffering from these diseases will have their own immune system attacking specific parts of their body. Today I will talk about two common ones: diabetes type I and multiple sclerosis [source].

Type I diabetes is caused by an immune attack against the beta-cells in the pancreas. This results in a complete loss of insulin. Insulin is a hormone essential for glucose control. When you eat something containing carbohydrates, the body will break them down into glucose, and it will go into the blood. Insulin will then make sure that the cell will pick up the glucose to use it as energy. In type I diabetes, the absence of insulin prevents the cell from using glucose, causing hyperglycemia, which means too much glucose in the blood. It causes intense hunger and thirst, and dangerous weight loss. Unfortunately, there is no cure to type I diabetes, and we do not know why the disease occur. There is a treatment however, which is simply to inject insulin to allow the body to use glucose [source / source / source / source].

Multiple sclerosis is a more complicated disease that involves the neurons. People with multiple sclerosis have an immune attack against a part of the neurons called the myelin. It results in neurons being less efficient. It results in many symptoms such as vision or motor problems, balance issues, and more. Multiple sclerosis is unique to every individual, making it very difficult to treat. Worse, many cases worsen over time: for every immune attack, the symptoms get stronger and stronger. Unfortunately, there is no cure for this disease either, and treatment will only prevent the worsening of symptoms. The cause of multiple sclerosis is unclear, but there are evidence of a strong environmental cause such as viral infection or smoking [source / source / source].

Immunodeficiency, or the lack of the immune system

Like the name suggest, immunodeficiency is the absence of an immune system. More commonly, no lymphocytes are present or functional. These disorders are particularly dangerous because while they won’t kill you by themselves, any infection following it will. The two most common cases of immunodeficiency are AIDS and SCID.

AIDS, or Acquired ImmunoDeficiency Syndrome, is the advanced disease caused by the HIV virus. When a person is infected with HIV, the virus will enter CD4 T lymphocyte and prevent their normal function. This will lead to a dysfunctional immune response. If HIV persists and is not removed, some unknown mechanisms cause the complete stop of CD4 T lymphocyte formation, and the immune system is completely inhibited. Again, there are no cure, but if diagnosed soon, living with HIV/AIDS is very manageable. IF the HIV virus is found early on, it can be eliminated, preventing the development of AIDS. [source / source].

SCID, or severe combined immunodeficiency, is a disease affected newborn where they completely lack lymphocytes. Any disease or infection is now deadly. The only cure for SCID is a bone marrow transplant. This syndrome was made famous because of a boy named David Vetter, who suffered from SCID. No transplant was available for him, thus he lived in a bubble in a hospital to protect him from germs. He survived for 12 years, which is very high considering that newborn with SCID at the time died very early. This story influenced the movie Bubble boy [source / source].

This article marks the end of the story on the immune system. There is of course much more to study and understand, but this series is a good start. I hope that I made the topic interesting, and don’t worry, we will come back to the immune system very soon, when we go into microbiology.

The Immune System II

Le par julienforsciencedans Immunology / ImmunologieLaisser un commentaire
The adaptive immune system

This is our second episode on the epic saga that is the immune system. Last week, we talked about the innate immune system, or the rapid way our body answers to a threat. Today, we will talk about the adaptive immune system, a response much slower than the innate one but more deadly. It has evolved to be specific to the threat that is presented, allowing it to hone in on the flaws of the pathogen and remove it very fast.

Where we left of, everything was wrong for our body: our skin fortress was down and compromised, and the leukocytes were not able to kill the pathogens. That’s when our messenger the dendritic cell left, but not without taking the antigen. The dendritic cell left to special immune hubs named lymph nodes. These structures are located all around your body and only contain a special kind of leukocyte: the lymphocytes. These lymphocytes are the heavy hitters in the immune system. But first, they need to be activated. Once the dendritic cell arrives at the lymph node closest to the site of infection, it will present its antigen to every lymphocyte present. Many of them will not do anything because they do not have the receptor that recognizes the antigen. However, once a lymphocyte has recognized the antigen, it will get activated and multiply in great number, causing the expansion of the lymph node. This is why for example when you have a sore throat the doctor is touching the side of your throat: we can feel the lymph node expanding, which indicates that there is an infection. Once ready, it will leave the lymph node and prepare for the attack. To better understand the adaptive immune system, I will go through different kind of lymphocytes one by one and present their functions [source / source / source].

The B lymphocytes: the snipers of the immune system

The first lymphocyte is called a B cell. It possesses a receptor conveniently called the B cell receptor (BCR), which recognizes the antigen. Once at the site of infection, it can do two things: first, it can phagocytose a pathogen and act like a dendritic cell, to activate other lymph nodes if needed, but more importantly, it becomes a plasma cell, and produces antibodies. Antibodies (also called immunoglobulins if you want to shine at parties) are proteins that have the same specificity as the BCR, which means that they can bind the pathogen. The plasma cell will produce many antibodies, which will trap the pathogen, preventing it to move. It is then easier for macrophages to phagocytose it and destroy it. Antibodies and plasma cells are key parts of what is called the humoral immunity: they protect the blood and other tissues from pathogens that do not enter cells, the extracellular pathogens [source / source / source].

The CD8 T lymphocytes: the brawlers of the immune system

Other that the B cells, the other type of lymphocytes are the T cells. These have another conveniently named receptor, the T cell receptor (TCR), which recognizes the antigen and allows for activation and multiplication. But T cells also have another receptor, either CD4 or CD8. We will start by talking about CD8 T cells, also called cytotoxic T cells. Once at the site of infection, CD8 T cell will focus on infected cells: they will bind them and either kill them by creating holes through the membrane, just like NK cells, or force a mechanism called apoptosis, a form of programmed cell suicide. We will talk more about apoptosis in upcoming articles, but it overall causes the cell to implode on itself and die. T cells are part of what’s called the cellular immunity: their aim is to protect non-infected cells from infection by targeting infected cells. They work best against pathogens that lives inside cells, the intracellular pathogens [source / source].

The CD4 T lymphocytes: the master tacticians

CD4 T cells, also called helper T cells, are activated the same way as CD8 T cells. However, their function is very different: they act as immune regulator. Upon being activated and by seeing the pathogen in action, the CD4 T cell will be able to determine what is the best attack against the pathogen. For instance, if we are attacked by a virus, the CD4 T cells will see the presence of intracellular pathogens and make the CD8 T cells more active and stronger, while B cells will stay a bit less active. The opposite is true if we encounter an extracellular pathogen: B cells will be stronger and the CD8 T cells will be a bit weaker. They work by first maturing into a specific CD4 subset. In the presence of extracellular pathogens, they become CD4 Th2 cells. In the presence of intracellular pathogens, they become CD4 Th1 cells. Each subset will release specific cytokines that will help overcome the threat. Many other subset exists, one of which we will discover next week, and several subsets can exist simultaneously depending on the pathogen. CD4 T cells are what makes the adaptive immune system so strong: they make the body adapt and evolve directly based on the threat to better fight it [source / source].

The innate and adaptive immune system are the core of any immune response, and each have a very specific role: the former is very fast and stereotypical, acting the same way every time, allowing for a quick removal of weak threat. The latter is slower but very specific. If a threat is strong, it will adapt to its flaws and remove the threat more efficiently. But both immune responses are interconnected: the adaptive response cannot start without the innate, and during an adaptive response, innate players such as macrophages are still actively working to remove the threat. Once again however, this system is not as perfect as it seems, otherwise we would never get very sick. Many pathogens have evolved to use the adaptive immune response to their advantage, and we will see one example in a few weeks. Next week, we will look at the aftermath of an immune response: the body won and the pathogen is destroyed; how do we calm the immune system down to prevent damages? And more importantly, how can we make sure that the next time we encounter this pathogen, it will be destroyed faster?

The Immune System I

Le par julienforsciencedans Immunology / ImmunologieLaisser un commentaire
The innate immune system

This article will start a series of article on the immune system. This topic is what made me go into science, and get my degree in immunology. First, I found it fascinating how well « thought-out » the immune system is: through centuries of evolution, the immune system adapted to so many different environments that it is able to protect us from virtually anything. It also have many failsafe mechanisms that in theory, it is an invincible system. However, we will see that it is not the case. I also loved the immune system because it is often presented like an epic battle. Learning immunology was more like listening to fairytales that were happening within our own bodies. This specific article will talk about the innate immune system. This is the first line of defense our body has.

Like any epic stories, we first need to introduce the opponents: our body is the good guy, or in scientific terms, the self. The bad guys can be any viruses, bacteria or pathogen that want to infect us. We call them the nonself. The self vs nonself discrimination is at the core of the immune system: any molecule identified as nonself will trigger the immune system. On the contrary, molecules that are from our body will not be attacked. This differentiation is essential for our survival and in later articles we will see that failure to differentiate self and nonself leads to diseases. [source].

When the pathogen decides to attack us, it has to go through our fortress first. It is composed of our skin, our intestines, or any part of our body that can be in contact with outside molecules. However, the pathogen is tricky: it will try to disguise itself to enter the cells. That’s when the cells in our fortress intervene: when the pathogen interacts with the cells, it will bind to proteins called pattern recognition receptors (PRR), and as their name suggest, they try to estimate whether the molecule is self or nonself based on patterns they already know. If the pathogen is recognized as nonself, the alarm is rung. The cells will produce a bunch of proteins to start the immune attack. These proteins are called cytokines, which have various effects depending on the cytokine produced. One of them is to act like messengers. They will tell the body where it is attacked and start a process called inflammation [source / source].

Inflammation is one of the biggest reaction during the immune attack. The release of cytokines will increase the blood flow towards the site of attack. This will help the attacking cells to come for help. Inflammation is always accompanied with these four symptoms: heat, swelling, redness, and pain. Most of these are caused by the influx of blood, except pain, which is due to cytokines activating neurons. While our fortress was holding off the pathogen, more competent cells have arrived at the site of infection. These cells are collectively known as white blood cells, or leukocytes [source / source].

Now the real fight is starting: The fortress was not able to hold off the pathogen, and there is a new problem: most pathogen either hide or reproduce within our own cells, especially viruses. Therefore, cells in our fortress are likely compromised. Infected cells are dangerous: in cases of viruses for example, infected cell will have viral DNA or RNA and express it, which can either cause many other viruses to be produced or kill off leukocytes. Leukocytes now have to fight infected cells and prevent the pathogen to enter the bloodstream. If it does, it will be able to spread in the entire body and cause massive damage. Leukocytes have many ways of preventing this, but I will only mention two. The first one if phagocytosis. Phagocytosis simply means eating cells. Several leukocyte have phagocytotic activities. One of them is the macrophage. It is able to eat pathogens that do not enter cells, like bacteria, and destroy them. It can also eat cellular debris, which contain dangerous pathogenic material. The second one is a way to kill infected cells. Since these cells express proteins from the pathogens, they can be recognized by leukocytes. One such leukocyte is accurately named the natural killer cell, or NK cell. These cells will attach to infected cells and release proteins to perforate the cell. And like a balloon, these cells will lose everything that is inside them and die. The macrophages then pick up the debris to finish up. There are many other ways the leukocytes work but these are the most common ways. [source / source / source].

At this point, this battle can have two outcomes. Either the leukocytes win, and the body is protected. If the pathogen wins, then the body requires more help. For this, a leukocyte named dendritic cell will act as a messenger: they will phagocytose a pathogen and keep a tiny piece of it, called an antigen. It will then exit the infection site and activate the second part of the immune system: the adaptive immunity [source / source].

This is the end of our first « episode » on the immune system. The innate immune system is an essential part of our defense: it is fast, and it is very efficient. It is so efficient that the innate immune system is almost the same in every vertebrate, and even the fly has a very similar innate immune system [source]. Its mechanisms have adapted through the years to offer us a great protection. But there is a flip side to this coin: the pathogens have also adapted to us. Every single event I have mentioned today can be neutralized, blocked, or evaded by some pathogens. Even the self vs nonself discrimination can be tricked. This is also why I love studying the immune system: there is an eternal tug of war between our body and the pathogens, and it will only make us stronger, but being able to study it can make the body even better at protecting itself. Next week, we will continue to follow our dendritic cell and see how it can bring more help.