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Lesson Video: The Nonspecific Immune Response Biology

In this video, we will describe how the body prevents pathogen entry and explain ways in which the nonspecific immune system responds to a pathogen invasion.

13:25

Video Transcript

In this video, we’ll find out all about the nonspecific immune response, the innate human system, which acts to prevent infection by pesky pathogens. We’ll explore the structures, secretions, and reflexes which limit the entry of infectious agents into the body. And we’ll discover how the processes of inflammation and phagocytosis work together to target pathogens that manage to evade this first line of defense.

It all begins with a pathogen. This can be a bacterium, a fungus, a virus, or even a protist. These biological agents are not harmful in themselves. But if they gain the ability to infect a host, such as a human, and cause disease, they become dangerous, with the potential to make us really ill. This is when we refer to them as pathogens. When pathogens are preparing to invade, the human body has only one option. It must defend itself against attack in order to survive. And luckily for us, it has a specialized system for doing just that, the immune system.

The human immune system has three lines of defense. The first comprises all the mechanisms which stop the pathogen from getting inside the body in the first place. The second line of defense involves a chemical and cellular response, which is nonspecific. In other words, it protects us against all pathogens in the same way, which means it can happen very rapidly. The third line of defense involves a chemical and cellular response that’s specific to the pathogen that’s causing the infection. This is known as the adaptive or acquired immune response. And it typically takes between four and seven days to be initiated in someone who is otherwise healthy. For someone with an underlying health condition, it can take even longer than this.

The first and second lines of defense are known collectively as the innate or nonspecific immune response. This is initiated immediately and can keep serious infections at bay while the adaptive immune response is being prepared. In this video, we’ll be concentrating on the nonspecific immune response. So let’s start by having a closer look at the first-line defenses the pathogen will encounter when it tries to invade.

The skin is the body’s largest organ, covering and protecting all of its external surfaces. It therefore acts as a physical barrier to pathogen entry. While the skin protects the external surfaces, the human body has many natural openings and internal surfaces that pathogens could use to get inside. These are protected by mucous membranes. As the name suggests, mucous membranes secrete sticky mucus, which lines the internal surfaces and traps any pathogens that try and get inside.

Mucous membranes are primarily found in the eyes, the ears, the nose, the mouth, the airways, the anus, and the vagina. The eyes are also protected by fluid secreted from the lacrimal glands. This fluid forms our tears. As well as being able to flush foreign matter, like dust, away from the eyes, tears also contain enzymes which can destroy certain bacteria. The ears also have a second protective secretion in the form of earwax, which has the scientific name cerumen. Cerumen is produced by the outer ear and works by trapping pathogens and other foreign material. It has also been shown to have some antimicrobial and antifungal properties.

Saliva, which is produced in the mouth by the salivary glands, contains enzymes which can destroy some types of bacteria. In addition to mucus secretion, some mucous membranes, such as those which line the airways, contain ciliated epithelial tissue. Cells of this ciliated epithelium have tiny hair-like structures on their surface called cilia. The cilia are there to waft mucus containing trapped pathogens and other foreign materials back up the airways to be swallowed.

Anything that gets swallowed ends up in the stomach. The stomach contains gastric juices, which have a pH of around two, meaning they’re highly acidic. Most pathogens that enter the stomach, either in our food or in mucus from our airways, will be destroyed by this acid.

The final kind of first-line defenses are the expulsive reflexes. These are reflexes which forcefully expel potentially infectious agents from the body. The best examples of expulsive reflexes are coughing, which expels material from the airways; sneezing, which expels material from the nose; and vomiting, which expels material from the stomach.

Despite all these mechanisms, some pathogens still manage to fight their way into the body. But just because they’ve managed to breach the first line of defense, it doesn’t mean things are gonna get any easier for them. It’s now time for them to face the second line of defense.

When pathogens get into the body and infect a particular tissue, in this example when bacteria infect the skin through an open wound, the site of infection immediately becomes reddened, swollen, painful, and hot. These are all effects of the inflammatory response or inflammation.

Let’s examine this response in a bit more detail. The skin is home to a particular type of white blood cell called a mast cell. Mast cells detect injury or infection and respond by releasing a chemical called histamine, as represented by the yellow dots on this diagram. Histamine causes the blood vessels in the skin to increase in diameter, allowing more blood to flow to the site of infection. This is known as vasodilation, and it’s the reason why the infected area becomes hot and red. Histamine also makes the capillaries more permeable, allowing more fluid to enter the tissues of the skin from the blood. This explains the swelling.

As well as histamine, mast cells also release other chemicals called cytokines, shown here as green dots. Cytokines are responsible for attracting phagocytes, another type of white blood cell, to the site of infection. Because of the increased blood flow and permeability of the capillaries, lots of phagocytes are able to migrate to the infected area really quickly. Later, the cytokines will attract other important types of white blood cell, but they’re part of the specific immune response. So we won’t be looking at them in this video.

Once our army of phagocytes have located the infecting bacteria, they must attempt to take out these pathogenic invaders the only way they know how, by a process called phagocytosis. This is where a phagocyte engulfs a pathogen before digesting it with enzymes.

Let’s have a look at the five stages which describe this process. Stage one is membrane binding. This is where receptors on the membrane of the phagocyte recognize and bind to proteins on the surface of the pathogen. Next, the pathogen is engulfed by the phagocyte, forming a specialized organelle called a phagosome. Although it looks a bit like the pathogen is eaten by the phagocyte at this stage, we need to make sure we use the word “engulf” instead of “eat” because a phagocyte doesn’t have a mouth or a digestive system. So it can’t actually eat anything.

Stage three is where the phagosome fuses with lysosomes. You may recall that lysosomes are membrane-bound organelles containing enzymes that work best under acidic conditions. When they fuse with a phagosome, a large vesicle called a phagolysosome is formed. During stage four, the pathogen is neutralized and digested by enzymes inside the phagolysosome. The harmless products of pathogen digestion are then either released from the phagocyte or presented on its cell surface membrane as part of the specific immune response. Although phagocytosis will destroy most pathogens, some bacteria, such as those which cause leprosy and tuberculosis, are thought to survive and escape the phagolysosome, which is why these diseases can be so dangerous.

In addition to phagocytosis, there are several other mechanisms which form part of the nonspecific immune response. Natural killer cells are a type of white blood cell which can recognize stressed body cells. If a body cell is under stress, it can be a sign that it’s either infected with a pathogen, such as a virus, or that it’s a tumor cell, which is proliferating uncontrollably. If a natural killer cell detects a stressed body cell, it will destroy it.

As we’ve already seen, cytokines are chemicals which play an important role in cell-to-cell communication during an immune response. Interferon is a cytokine which is produced by body cells that have been infected with a virus. It acts on nearby cells to inhibit viral replication. If the virus can’t replicate, then the infection won’t be able to spread as quickly. Interferon is also responsible for activating natural killer cells.

Finally, the complement system is a collection of soluble proteins found in the blood. They work together in what’s known as a complement cascade to form an attack complex. This complex makes holes in the cell membranes of invading bacteria, destroying them. Proteins of the complement system are also involved in promoting inflammation and stimulating phagocytes to initiate phagocytosis.

Now, let’s find out what happens when these immune responses malfunction. The reason we feel ill when we have an infection is largely down to the inflammatory response that we’ve already talked about. As you can see on this graph, the inflammatory response is initiated upon infection and increases rapidly. After about a week, it falls back down again as the immune system clears the pathogen from the body. This is when we start to feel better.

However, in some circumstances, the level of inflammation can remain very high, as represented by the blue line on the graph. This is known as chronic inflammation and can lead to a number of different health problems. Although we still don’t fully understand all the causes of chronic inflammation, we do know that they can either be infectious or noninfectious. Some pathogens are able to evade our immune system and, therefore, can’t be fully cleared from the body. Gut microbes that we ingest in our food can also sometimes activate the inflammatory response inappropriately. These are examples of infectious causes. Noninfectious causes include obesity and tissue damage resulting from tumors, autoimmune disorders, atherosclerosis, and heart disease.

Chronic inflammation can cause permanent changes to the tissues, such as cell death, scarring, blood vessel growth, and cell proliferation. It can also be responsible for metabolic changes, for example, impaired hormone signaling. These changes can ultimately lead to a number of serious conditions, including type two diabetes, organ failure, cancer, and Alzheimer’s.

Now we’ve learnt all about the nonspecific immune response, let’s have a go at a practice question.

How does histamine affect blood vessels near an injured area? (A) It dilates blood vessels and decreases capillary permeability. (B) It dilates blood vessels and increases capillary permeability. (C) It dilates blood vessels but does not affect capillary permeability. (D) It constricts blood vessels but does not affect capillary permeability. Or (E) it constricts blood vessels and increases capillary permeability.

When we injure ourselves, the affected area quickly becomes red, swollen, painful, and hot. Although this is pretty unpleasant for us, it’s actually a sign that the body is reacting to the injury and beginning to repair itself. It does this through a nonspecific immune response known as inflammation.

Inflammation, which is sometimes called the inflammatory response, is initiated by a special type of white blood cell called a mast cell. Mast cells detect injury or infection and respond by releasing a chemical called histamine. This is what the question is asking us about. Histamine has two important effects on the blood vessels near the site of injury. The first is that it causes them to dilate, allowing more blood to flow to the injured area. This is known as vasodilation, and it’s what causes the redness and heat. As answer options (D) and (E) say the blood vessels constrict, which means that they become narrower, these options must be incorrect.

The second effect of histamine is that it increases the permeability of capillaries near the site of injury. This allows more fluid to enter the injured area from the blood, bringing with it specialized white blood cells, such as phagocytes, which can help to clear any infection. This is what causes the swelling. We have therefore determined how histamine affects blood vessels near an injured area. The correct answer is (B). It dilates blood vessels and increases capillary permeability.

Let’s summarize what we’ve learnt in this video by reviewing the key points. The first line of defense is a collection of mechanisms which prevent pathogens from getting inside the body. Inflammation and phagocytosis are key processes in the second line of defense. Inflammation is initiated and regulated by chemical messengers. Phagocytes help to clear infection by engulfing pathogens. And other mechanisms in the nonspecific immune response also have important roles to play.

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