Transcription
So far we looked at how the body responds to damage through inflammation and cellular level mechanisms. Now we will move on to the next major topic, immunology.
The responses of the immune system can sometimes become a cause of disease themselves. In general, immunological disorders are divided into four main groups, which you can see here. Hypersensitivity reactions, also known as just hypersensitivities, are one of these groups. These represent situations where the immune system becomes a source of pathology rather than protection. So first, we will focus on these hypersensitivity reactions. These are exaggerated or misdirected immune responses that can damage the body's own tissues. And also, there are four classical types, each with a different underlying mechanism. We will spend most of the time looking at type one hypersensitivity. The first type of hypersensitivity is the fastest, the most common, and also the most dangerous reaction. That's why we will look at it in more detail compared to other types.
In general, all hypersensitivity reactions mean that the immune system does not protect the body. Instead, it attacks it. What differs between these types is the mechanism and the main components involved. In this case, the key players are IgE antibodies, or immunoglobulin E. Essentially, what we are talking about here are allergies, because this type accounts for most allergic reactions. The antigens that trigger these reactions are called allergens. Allergies are reactions to substances that come from outside the body. Substances that most people do not react to, but some individuals do.
In some cases, whether something becomes an allergen depends on genetic factors, although there can be exceptions. For example, there is a species of tick found in the United States that can trigger an unusual immune response. After being bitten, a person may develop a long-term allergy to red meat, such as pork and beef. Okay, chicken and fish then are still fair game. But in general, the person cannot eat pork and beef for the rest of their lives. That is pretty awful if you ask me.
Now, returning to allergies in general. An allergic reaction occurs in two phases. The first phase is the initial exposure, called sensitization. During this phase, there are no visible symptoms yet. The second phase is the re-exposure to the same allergen, which can happen even years later. This is when the actual allergic reaction occurs.
A key role in this process is played by a subtype of T lymphocytes known as helper T cells. These cells help determine which substances are recognized as allergens. If they become hypersensitive to a specific substance, this can lead to the development of an allergic reaction. So, how does this actually happen? Let's imagine a person who inhales a specific type of pollen for the first time. So, my example will be with pollen here.
First, the antigen is recognized by immune cells located along the mucous membranes of the airways. These cells capture the molecule through endocytosis, and then these immune cells migrate to the lymph nodes. These immune cells can include macrophages, for example, but also other immune cells. Importantly, this process of capturing the substance and transporting it to the lymph nodes happens regardless of whether the person is allergic to it or not. It is a normal function of the immune system, which constantly monitors and evaluates substances entering the body, checking whether they might be harmful.
Next, in the lymph node, this foreign substance, whether we call it an antigen or, in this case, an allergen, is presented to a T lymphocyte, specifically a helper T cell. If this substance is recognized as an allergen, the helper T cell then signals B lymphocytes to produce antibodies. However, instead of producing the usual antibodies like IgM, the B cells are instructed to produce IgE antibodies. These IgE antibodies are highly specific. They are directed against the particular allergen that entered the body. For example, a specific type of pollen, which we are discussing here.
At the same time, there is often a broader genetic predisposition, meaning that if someone is allergic to one type of pollen, they may also react to multiple related pollens. However, the antibodies themselves remain specific to the exact allergen that triggered their production. This communication between T helper cells and B lymphocytes only occurs if there's a genetic basis for recognizing that substance as an allergen. If this predisposition is not present, the process stops at antigen presentation, and no allergic response develops. In fact, as I said, most substances we encounter are presented to helper T cells. But in the majority of people, these cells simply do not respond. For most individuals, substances like pollen do not trigger any further immune activity at all. But in cases where this communication does occur and IgE antibodies are produced, the stage is set for the allergic reaction.
Next, what happens to these antibodies? So, firstly, they attach to mast cells. So, here we have again mast cells as a very important cell type. So, you probably notice that mast cells play quite a significant role in this lecture. So, once the IgE antibodies have attached, the sensitization phase is complete. After that, nothing happens until the person comes into contact again with the same pollen or other allergen.
So, now we have the second exposure. This time, the antigen or allergen binds to the specific IgE antibodies which were there already attached to the mast cell. This binding then gives a signal to the mast cell. And as you can see here, the result of the signal is, in the picture, vomiting of the mast cell, which represents release of various substances from this immune cell. And these substances released are various inflammatory mediators. One of the most important substances released, as you know, is histamine, and we already know quite a lot about what histamine does. It causes vasodilation, increases capillary permeability, and also leads to bronchoconstriction in the airways. Since the blood vessels are now wider and, so to say, more leaky, there is increased blood flow, but at the same time, fluid also leaks out. The result is swelling and can also lead to urticaria, or in other words, hives, as additional effects of this process.
In addition, mast cells also release various substances to attract other leukocytes, including, for example, eosinophils, basophils, and neutrophils. They also release cytokines and leukotrienes. As I already mentioned, leukotrienes are particularly important in bronchoconstriction, and they also cause airway spasms and, at the same time, attract these other immune cells that I just mentioned. These cells then arrive, so to speak, to deal with the antigen, which in this case is actually not harmful at all.
For most people, these allergic symptoms are relatively mild. They may appear as hives, as I said, eczema, itchy rashes, or allergic rhinitis, which means a runny nose. Allergic asthma can also occur. However, in some individuals, there can be very strong reactions to specific allergens, such as shellfish. Okay, this is not shellfish, but seafood could be also any other seafood besides shellfish, peanuts, or bee venom. In these cases, these immune responses become extremely intense, leading to a rapid drop in blood pressure. This means that the brain and other organs are no longer sufficiently supplied with oxygen. Breathing difficulties also develop due to strong bronchoconstriction. And additionally, there can be various skin symptoms, palpitations, dizziness, and even loss of consciousness. Swelling of the throat, tongue, or face is especially dangerous because it can lead to suffocation, and this severe reaction is called anaphylactic shock. In such cases, the patient is given epinephrine, so adrenaline, which helps constrict blood vessels and dilate the bronchi, essentially counteracting these effects written here. And of course, emergency medical help must be called immediately.
So, this is type one hypersensitivity. Now let's move on to the second type of hypersensitivity. I won't go into as much detail here as with the first type, but it is still important to understand the main idea. This type is also called the cytotoxic hypersensitivity. Cyto meaning cell, and toxic meaning damaging. In this case, the immune system targets the body's own cells, but very specific ones. The antibodies involved here are mainly IgG and IgM. And these antibodies bind to specific cells which are mistakenly recognized as foreign. In most cases, this misrecognition has a genetic basis, meaning the immune system incorrectly identifies certain cells as harmful.
One example is autoimmune hemolytic anemia, where the immune system attacks red blood cells, leading to their destruction and resulting in anemia. Of course, another example is Graves' disease, which leads to hyperthyroidism. In this case, antibodies bind to receptors on thyroid cells and continuously stimulate them, causing excessive production of thyroid hormones. And the third example here is myasthenia gravis, which works in the opposite way. Here, antibodies bind to acetylcholine receptors in skeletal muscles. I have called them here acetylcholine receptors, but probably you know from physiology that these are nicotinic type receptors. Anyway, as a result, acetylcholine cannot bind to these receptors because they are occupied with the antibodies, and that means muscle contraction is impaired over time. This leads to muscle weakness and atrophy.
Moving on to the third type of hypersensitivity. In this case, the main problem is caused by antigen-antibody complexes, also known as immune complexes, which form in the bloodstream. After forming, these complexes can deposit in tissues. The antibodies involved here are again mainly IgG and IgM. The key issue is an imbalance between the formation of these immune complexes and their removal from the body. For example, if processes like phagocytosis are not efficient enough, these complexes are not cleared properly. As a result, they accumulate in tissues. In addition, the complement system is also activated, which further amplifies the inflammatory response, and in the end, this leads to inflammation and tissue damage.
And finally, the fourth type of hypersensitivity. This is the only type that is not mediated by antibodies. Instead, the main players here are T lymphocytes. Functionally, these T cells are working correctly, but their response is either inappropriate or excessive, which leads to tissue damage. As a result, a localized inflammatory reaction develops. This type of reaction is slower than antibody-mediated responses. It typically develops over 24 hours or even more. However, because it is usually localized, the consequences are generally less severe.
A common example is contact dermatitis, such as a reaction to nickel. In such cases, the solution is usually simple: avoiding contact with the triggering substance. Another example you may encounter is latex-induced contact dermatitis, which can be managed by using alternative materials in gloves, for example. A non-pathological example of this reaction is the tuberculin, or also called Mantoux, test. In this test, bacterial proteins are injected into the skin, and after 24 hours or more, the local reaction is observed. Based on this response, we can determine whether a person has previously been exposed to tuberculosis or not.
And so, this completes our overview of hypersensitivity reactions. The next category is autoimmune diseases. In simple terms, these are conditions in which the immune system is unable to distinguish between the body's own cells and foreign substances. As a result, it begins to attack the body's own tissues. Autoimmune diseases can be divided into two main types. They may be organ-specific, where only one organ is affected, or systemic, where multiple organs or systems are involved. Unfortunately, these diseases are often chronic and progressive, and they can affect several systems in the body at the same time.
At this point, you may wonder, how does this differ from hypersensitivity reactions? Well, in reality, there is a significant overlap. Many autoimmune diseases can actually be classified within specific hypersensitivity types, meaning these are not completely separate categories. In essence, autoimmunity is a form of hypersensitivity directed against the body's own tissues. So, a few examples here. An organ-specific autoimmune disease is type 1 diabetes, where the immune system targets the pancreas, damaging insulin-producing beta cells. A systemic example is rheumatoid arthritis, which affects multiple joints and systems. And rheumatoid arthritis is also a good example of overlap, as it involves immune complex formation. This is type 3 hypersensitivity, and as it involves T cell-mediated chronic inflammation, this involves type 4 hypersensitivity. So, as you can see, in immunology, the boundaries between different conditions often overlap rather than being strictly separated.
Now let's move on to something quite different: immunodeficiencies. In contrast to autoimmunity, where the immune system is overactive, here we see the opposite. The immune system is too weak. Immunodeficiencies can be divided into primary (congenital) and secondary (acquired) forms. Congenital immunodeficiencies are caused by genetic mutations and usually present in childhood. Examples include conditions like Bruton's agammaglobulinemia, where B lymphocytes are absent and therefore antibodies are not produced, or DiGeorge syndrome, where T lymphocytes are lacking. However, these are not something we will focus on in detail here.
More relevant and also frequent are acquired immunodeficiencies, where the immune system becomes weakened over time due to external factors. One of the most well-known examples is HIV infection. The virus destroys T lymphocytes, leading to a gradual breakdown of the immune system, which can result in AIDS, especially if no treatment is provided. But HIV is not the only cause. Other factors can also weaken the immune system. For example, severe malnutrition can significantly impair immune function. Certain treatments, such as chemotherapy, as well as cancer itself, can also lead to immunodeficiency. So, overall, immunodeficiency represents a state where the body's ability to defend itself is reduced, making it more vulnerable to infections.
Finally, the last category we will discuss is transplant rejection. In this case, it is quite intuitive. The body recognizes the transplanted organ as something foreign. There are three types of rejection. The first is hyperacute rejection, which occurs almost immediately after transplantation. It happens when the recipient already has antibodies against the donor's antigens, and this leads to severe outcomes such as thrombosis and tissue necrosis, and is usually prevented by carefully matching donors and recipients.
The second type is acute rejection, which is the most commonly encountered. It develops days to weeks after transplantation and is mainly driven by T lymphocytes attacking the transplanted organ. This type can be treated with immunosuppressive drugs. However, these drugs weaken the immune system, connecting back to what we discussed about immunodeficiency, but they are necessary to prevent this rejection.
And the third type is chronic rejection, which develops over months to years. It is a slower process involving a long-term, low-grade immune response that gradually leads to loss of organ function. Unfortunately, chronic rejection is usually irreversible. While treatment can slow it down, it cannot fully restore the organ.
So, as you can see, immunology includes a wide range of complex mechanisms where the immune system itself becomes the source of the problem. We have only briefly touched on the main categories: hypersensitivity reactions, which are excessive responses to external stimuli; autoimmune diseases, where the body attacks its own tissues; immunodeficiencies, where the immune system is too weak; and transplant rejection, where the immune system rejects foreign tissue. But this concludes then our brief introduction to immunopathology.