Lesson Explainer: The Nonspecific Immune Response Biology

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

They say the best offense is a good defense. Luckily, the human body has several defensive systems that prevent our bodies from having to fight infections by simply keeping most pathogens out! The nonspecific immune response is the body’s method of preventing the entry of pathogens as well as rapidly responding to the first signs of potential infection.

A pathogen is an organism or agent that can infect a host and cause disease. Common pathogens include microorganisms like bacteria or fungi and nonliving entities like viruses, prions, and viroids. An antigen is a substance that initiates an immune response. Antigens and pathogens are related. Pathogens may have antigens on their surface or secrete antigens such as toxins that are dangerous to cells. The relationship between pathogens and antigens is shown in Figure 1.

Figure 1: A diagram demonstrating how a pathogen (a disease-causing agent) can have two different antigens on its surface.

The immune system can act as a barrier to pathogens, and it can do this in physical or chemical ways. These physical barriers involve the epithelium of the skin because these cells form tight junctions between each other to physically prevent pathogens from entering the body. Chemical barriers include the actions of the immune cells, the chemicals they produce, and other substances within the body that act to slow, damage, or destroy the pathogens that may have entered the body.

There are two main types of immune responses: nonspecific and specific. Specific immunity is also called adaptive immunity or acquired immunity. This is the part of the immune system that adapts to respond to a specific threat in a specific way. We call this type of response antigen specific. Adaptive, specific, immunity develops with your body over time.

Nonspecific immunity is also called innate immunity. It is the part of the immune system that reacts to every threat in the same way. Innate immunity is not antigen specific. Innate, nonspecific, immunity is immunity you are born with. A flow chart outlining the differences between innate immunity and adaptive immunity is shown in Figure 2.

Key Term: Nonspecific Immunity (Innate Immunity)

Nonspecific immunity is immunity you are born with that protects you against all pathogens in the same way.

Figure 2: The human immune system is commonly divided into innate, or nonspecific, immunity and adaptive, or specific, immunity.

Nonspecific, or innate, immunity begins with the barrier defenses, which are barriers that protect the internal environment from foreign particles and potential pathogens. These defenses can also be described as the “first line of defense.”

Every point of entry to our bodies (for example, our skin, eyes, ears, nose, and digestive system) has a specialized defense of its own.

The skin defines the boundaries of the human body. It covers and protects all of the external surfaces. Our skin also houses immune cells, such as mast cells, that rapidly respond to infection if the barrier is broken by an injury, such as a cut or a scrape.

Key Term: Mast Cell

A mast cell is an immune cell found in the skin that releases histamine in response to injury.

The surface of the skin is home to a community of bacteria that are harmless and sometimes beneficial. However, these same bacteria can pose a threat to our internal environment. This is one reason why the skin must function as a robust defense against invasion by potential pathogens.

While the skin protects the external surfaces, mucous membranes serve that same purpose when it comes to body cavities and internal surfaces. Mucous membranes are composed of one or more layers of epithelial cells, and they generally secrete mucus of some sort. The types of cells and types of mucus secreted vary by location. Mucous membranes are found in the eyes, ears, nose, mouth, vagina, urethra, and anus. The mucous membranes function to prevent dirt and pathogens from entering the body. A diagram of a mucosal epithelium is shown in Figure 3.

Figure 3: A diagram showing the cells of mucous membranes, which include ciliated epithelial cells to move mucus, and goblet cells that make and secrete mucus.

The mucous membranes of the ear are found in the middle and inner ear, the parts deep within our head. The outer ear produces a material called cerumen, also known as earwax. Cerumen is an additional barrier method of protection that prevents foreign materials from entering the ear. It has also been shown to have some antimicrobial and antifungal properties.

The mucous membranes of the eyes are found on the inner surfaces of the eyelids. The eyes are also protected and lubricated by tears. Tears are secretions of glands called lacrimal glands, or tear glands, found in the tissue surrounding the eye. The lacrimal glands are constantly secreting fluid that keeps the surface of the eye moist. This fluid also contains enzymes that can destroy certain bacteria. One of these enzymes is called lysozyme, and it has the ability to break open, or “lyse,” certain bacteria to kill them.

The lacrimal glands make more fluid when the surface of the eye is stimulated by contact with a foreign object, like dust, which helps to flush these objects from the eye. Dust and dirt can carry pathogens as well as cause physical damage to the delicate surface of the eye. The lacrimal glands also make the tears humans cry when we experience extreme emotions like joy or sadness.

Nearly the entire surface of the respiratory tract is lined with mucous membranes, from the nose and sinuses to the inside of the lungs. Mucus moistens the surfaces of the lungs, which allows dissolved gases like oxygen and carbon dioxide to pass through. Mucous membranes in the lungs also serve the purpose of trapping foreign particles and potential pathogens.

Key Term: Mucous Membrane

A mucous membrane is a specialized kind of epithelial tissue with cells that secrete mucus and can have ciliated cells that move the mucus from place to place.

Example 1: Recalling the Organs That Possess Goblet Cells

Goblet cells, like the one shown in the diagram, are mucus-secreting cells. They are present in mucous membranes throughout the body and the mucus they release traps pathogens and other foreign particles.

Which organ does not contain goblet cells?

  1. Skin
  2. Stomach
  3. Vagina
  4. Nose
  5. Trachea

Answer

Goblet cells are cells specialized to secrete a fluid called mucus. These mucus-secreting cells are found in mucous membranes. Mucous membranes possess a specialized type of epithelium, or lining tissue, that has some cells that are specialized to make mucus. Some mucous membranes also contain ciliated cells that are specialized to move the mucus from place to place.

In the immune system, mucous membranes function as an aspect of innate, or nonspecific, immunity. Innate immunity is immunity that responds to every pathogen in the same way. Another way to say this is that innate immunity is not antigen specific.

Innate immunity involves barrier immunity or physical and physiological factors that prevent pathogens from entering the body. If a pathogen makes it past the barriers, or first line of defense, the second line of innate immune defense is activated. This involves the action of some cells and chemical components that fight the pathogen to halt or slow the spread of infection.

Mucous membranes are barrier methods of immune defense. They are present as linings to most body cavities and points of entry into the internal environment of the body. The mucous membranes function to prevent dirt and pathogens from entering the body. Mucous membranes are found in the eyes, ears, nose, mouth, vagina, urethra, and anus.

This means that the organ that does not contain goblet cells is the skin.

The mucus in our airways is constantly moved by special cells called ciliated cells. These cells have hairlike structures that sweep the mucus in one direction, toward the throat. Anything trapped in the mucus of the airways is eventually swallowed and passed to the stomach. Excess mucus can cause coughing, which will more forcefully expel mucus and trapped foreign particles from the body through the mouth.

Coughing is an example of an expulsive reflex. Another example is sneezing. Expulsive reflexes are reflexes that forcefully expel foreign substances from the body. Coughing expels material from the airways leading to the lungs. Sneezing does the same for the nasal passages. Some pathogens, like respiratory viruses such as COVID-19, use these expulsive reflexes to their advantage to help them spread to new hosts.

Like the respiratory system, the digestive system is also nearly completely lined with mucous membranes. These membranes serve as barriers that protect the internal environment from foreign particles and potential pathogens. In addition to the protection the mucous membranes provide, different parts of the digestive system have additional defenses of their own.

For example, the saliva produced in the salivary glands of the mouth has enzymes in it that can destroy some types of bacteria.

The gastric juices of the stomach (HCl) have an extremely low pH, which means that they are very acidic. This acid serves to destroy most pathogens that enter the stomach either on our food or in the mucus that is transferred from the respiratory tract.

At every potential point of entry to the body, there are barriers that protect the internal environment from foreign particles and potential pathogens. This is what we sometimes call the first line of defense. However, there are some instances in which pathogens still manage to enter the body. This would activate the “second line of defense.”

Example 2: Identifying Physical Barriers to Pathogens

Which statement is an example of a physical barrier to pathogen entry?

  1. Complement proteins in blood
  2. Keratinized layers of epidermis
  3. Hydrochloric acid in the stomach
  4. Oils and salt in sweat
  5. Lysozyme in tears and saliva

Answer

The innate immune system, or nonspecific immunity, describes the part of the immune system that is not antigen specific. These are barriers and physiological responses that respond to every pathogen in the same way.

The barriers that are a part of the innate immune system are what we call the first line of defense against pathogens. They function to prevent pathogens from entering the body where they can cause damage and develop into illness and disease.

Some barriers are physical and keep foreign particles and pathogens out. Some are chemical like chemicals, enzymes, and other substances that slow, damage, or destroy pathogens that may enter or have entered the body.

Out of the answer choices presented, complement proteins in blood, hydrochloric acid in the stomach, oils and salt in sweat, and lysozyme in tears and saliva are all examples of chemicals and other substances. Many of these function as barriers to pathogens, but they are not purely physical in nature.

The keratinized layers of epidermis describe the outer layers of the skin. The skin is the physical barrier that protects all of the external surfaces of the body. The outer layers of cells are flat, irregular, and overlapping. They form a waterproof layer that is very effective at preventing the entry of pathogens.

This means that the example of a physical barrier is the keratinized layers of epidermis.

Imagine that you accidentally scrape your arm against something sharp and cut your skin. At first, you will experience bleeding and pain. The blood flushes pathogens out to prevent them from entering the blood vessels. The bleeding stops when a clot forms, which is a mass of blood cells that plug the wound. The blood clot contains many immune cells. This clot eventually forms a scab, which further protects the internal environment from invasion.

In addition to this response, you may almost immediately experience swelling, redness, and pain at the site of the wound that last for a number of hours or days after your initial injury. The heat, redness, and pain are all symptoms of an innate immune response called the inflammatory response, or inflammation.

Key Term: Inflammation

Inflammation is a reaction to injury or infection in which part of the body becomes reddened, swollen, painful, and hot.

We mentioned that the skin is home to immune cells, including mast cells. When these cells detect damage or injury to cells in the skin, they release histamine and cytokines. Cytokines are chemicals that facilitate communication between cells during an immune response. The cytokines and histamines initiate the inflammatory response. A diagram illustrating the stages of an inflammatory response after injury to the skin is shown in Figure 4.

Figure 4: A diagram showing the sequence of events, called an inflammatory response, that occurs in the skin in response to injury.

Histamine causes the capillaries and blood vessels in the skin to increase in diameter, allowing more blood to flow to the area around the wound. This is called vasodilation. The vasodilation is the source of the heat and redness. The word inflammation literally means “to inflame, or become hot.”

Histamine also makes the capillaries more permeable, allowing more fluid to leave the bloodstream and enter the tissues of the skin. This is the source of the swelling.

Key Term: Histamine

A histamine is a compound that is released by cells in response to injury and in allergic and inflammatory reactions. Histamine causes vasodilation.

Key Term: Vasodilation

Vasodilation is when blood vessels increase in diameter, which increases blood flow to an area.

Example 3: Recalling the Effect of Histamine on Blood Vessels

How does histamine affect blood vessels near an injured area?

  1. It constricts blood vessels but does not affect capillary permeability.
  2. It constricts blood vessels and increases capillary permeability.
  3. It dilates blood vessels and decreases capillary permeability.
  4. It dilates blood vessels but does not affect capillary permeability.
  5. It dilates blood vessels and increases capillary permeability.

Answer

There are two main types of immune responses: nonspecific and specific. Specific immunity is also called adaptive immunity or acquired immunity. This is the part of the immune system that adapts to respond to a specific threat in a specific way. Adaptive, specific, immunity develops with your body over time.

Nonspecific immunity is also called innate immunity. It is the part of the immune system that reacts to every threat in the same way. Innate, nonspecific, immunity is immunity you are born with.

Innate immunity begins with barrier defenses. These are barriers that protect the internal environment from foreign particles and potential pathogens. Skin is one of the body’s barriers. When the skin is damaged, the barrier is broken, and pathogens, like bacteria, can enter the body.

Histamine is released by mast cells and some other cells in response to injury to the skin or another part of the body. When our skin is damaged by a cut or a scrape, damaged cells send signals that trigger mast cells to release a chemical called histamine. The histamine sets into motion a series of events we collectively call an inflammatory response.

Inflammation literally means “to inflame.” It refers to the signs of inflammation, which are redness, heat, swelling, and pain. The histamine causes blood vessels near the site of the injury to become larger in diameter, which is called vasodilation. This allows more blood to flow through. This causes heat and redness. The histamine also triggers the blood vessels to become more permeable. This means that materials can pass into and out of the blood vessels more easily. Fluid from the blood is transferred to the tissue surrounding the injury, which leads to swelling. Additionally, cells called phagocytes migrate from the bloodstream to the injured area where they engulf any pathogens that may have entered the body.

Using this information, we can conclude that histamine affects blood vessels because it dilates blood vessels and increases capillary permeability.

The early stages of inflammation attract phagocytes: immune cells that can engulf pathogens using a process called phagocytosis. Phagocytosis forms a vesicle around the pathogen that is moved to the interior of the cell. Then, the pathogen can be destroyed or broken apart to allow the antigens to be displayed on the cell surface.

Phagocytosis proceeds according to the following stages:

  1. The pathogen is attached to the cell membrane.
  2. The pathogen is engulfed by the cell.
  3. The phagosome is formed.
  4. The phagosome and lysosome fuse to form phagolysosome.
  5. Lysosome enzymes neutralize and break apart the pathogen.
  6. Digested pathogen products are either released from the cell or presented on the cell surface as antigens.

The stages of phagocytosis are illustrated in Figure 5.

Figure 5: A diagram illustrating the process of phagocytosis, which is a type of endocytosis.

Phagocytic cells include macrophages, neutrophils, and other similar cells. These cells are able to easily migrate to the site of infection due to the increased blood flow and increased permeability of the capillaries.

Key Term: Phagocytosis

Phagocytosis is a form of endocytosis in which cells engulf and internalize solid matter such as a pathogen.

Example 4: Identifying Components of the Inflammatory Response to Skin Injury

The figure shows the cellular response to tissue injury after the skin has been broken by a nail.

What process is illustrated by cell X?

  1. Histamine release
  2. Phagocytosis
  3. Chemotaxis
  4. Edema (swelling)
  5. Clot formation

Answer

When our skin is damaged by a cut or a scrape, damaged cells send signals that set into motion a series of events we collectively call an inflammatory response. Inflammation literally means “to inflame.” It refers to the signs of inflammation, which are redness, heat, pain, and swelling. The histamine causes blood vessels near the site of the injury to become larger in diameter, which is called vasodilation. This allows more blood to flow through, which causes the heat and redness.

An inflammatory response is caused by the release of chemical messengers such as histamine and cytokines. The damaged cells in the skin trigger mast cells to release histamine, which causes vasodilation.

The histamine also triggers the blood vessels to become more permeable. This means that materials can pass into and out of the blood vessels more easily. Fluid from the blood is transferred to the tissue surrounding the injury, which leads to swelling. Additionally, cells called phagocytes migrate from the bloodstream to the injured area where they engulf any pathogens that may have entered the body.

Many types of immune cells are phagocytic, including neutrophils and macrophages. These phagocytic cells engulf pathogens by attaching to them using molecules on their cell surface and pulling them into the phagocytes’ interior. This forms a vesicle called a phagosome. The phagosome fuses with one or more lysosomes that are full of enzymes that break down the pathogen, destroying and neutralizing it. The remaining particles can be ejected from the cell by exocytosis. Some parts of the pathogen, called antigens, will be displayed on the cell surface to trigger further immune system actions.

Therefore, the process illustrated by cell X is phagocytosis.

Another cellular component of the innate immune response is a type of lymphocyte known as a natural killer cell, or NK cell. NK cells have the ability to recognize stressed, infected, or abnormal cells and eliminate them. Unlike the B and T lymphocytes, which are antigen specific and a part of the adaptive immune system, NK cells do not need to be activated by other immune cells or go through clonal selection where cells with more specificity toward an antigen are selected to produce more cells, a process that takes days, so they are able to respond rapidly to infection or to a growing tumor.

Another aspect of the innate immune system’s second line of defense is a series of proteins and their reactions known as the complement system. Complement enhances, or complements, the immune system’s various responses. It plays a role in both innate and adaptive immunity.

Complement proteins are always present in the blood. When they detect certain signs of infection, they work together with cytokines to activate a series of events called a complement cascade.

The complement cascade includes steps that aid in the progress of the inflammatory response, attracting and stimulating phagocytes that “eat” and destroy the pathogens. The complement system can also form a complex of chemicals that attacks and breaks apart the cell membrane of invading bacteria.

The second line of defense also includes some of the chemical messengers collectively known as cytokines. Cytokines function to facilitate communication between cells during an immune response.

An example of a cytokine functioning in the innate immune system is interferon. Interferon is a cytokine that is produced by host cells that are infected with a virus. Interferons interfere with virus replication in nearby host cells as a way of slowing the spread of infection. Interferons also stimulate the action of natural killer cells and macrophages. An illustration of the role of interferon is shown in Figure 6.

Figure 6: A diagram showing how a cell produces interferon when infected by a virus. The interferon is secreted and allows nearby cells to prevent the virus from replicating within them.

The chemical signals and cells involved in innate immunity are what we refer to as the second line of defense. These physiological responses are nonspecific, meaning they treat every pathogen the same way. Another way to say this is that they are not antigen specific.

After our skin is damaged by a cut or a scrape, inflammation works to clear any pathogens that may have been introduced. Normally, once any infection is cleared, cytokine and histamine levels drop and inflammation ends. However, this is not always the case and unregulated inflammation or immune function, such as autoimmune diseases, can lead to chronic inflammation.

Inflammation is an efficient and necessary immediate response to potential infection. However, inflammation can also be dangerous if left unregulated. Many autoimmune diseases, such as rheumatoid arthritis, lupus, and multiple sclerosis, have an inflammatory component where this system, which is designed to help our bodies, ends up attacking the body and causing injury instead.

Chronic inflammation, a low level of inflammation over a long period of time, has been linked to serious diseases like heart disease, type 2 diabetes, and cancer. Chronic inflammation has been shown to be caused by diets high in processed foods and destructive practices such as smoking and drinking alcohol. So, keeping your body healthy helps to keep your inflammation under control, which will prevent chronic disease.

It can take several days for the human adaptive immune system to mount a full response to an invading pathogen. During that time, the innate immune system is fighting off the infection by initiating inflammation like we have described. This inflammation, when occurring because of an infection somewhere besides the skin, can lead to the swelling, pain, and fever that we associate with the symptoms of many illnesses.

For example, a common infection of the tissue of the throat is one of several strains of streptococcus bacteria; we call it “strep throat.” Within a couple of days of being exposed to these bacteria, the host will experience soreness and swelling in the throat as well as fever. As the bacteria multiply in the throat tissue, they cause injury to the cells there that release the histamine that initiates the inflammatory response.

The symptoms we commonly associate with the early signs of illness are actually our innate immune system doing its job to keep an infection under control until the adaptive immune system can mount a specific attack on the pathogen.

Our innate immune system has the tools to prevent most infections by either keeping pathogens out of the body or eliminating them in the early stages of infection. The adaptive immune system only kicks in when innate defenses prove inadequate. The relative times, durations, and strengths of protection of the various lines of immune defense are shown in the graph in Figure 7.

Figure 7: A graph that compares the immunological protection by physical barriers, innate immunity, and acquired immunity.

This two-tier system is highly efficient, preserving the resources of the adaptive immune system for the most severe cases only. Alternatively, the innate immune system keeps serious infections under control while the adaptive immune system prepares to step in and eliminate the threat.

Key Points

  • The role of the nonspecific (innate) immune response is the immediate response to infections.
  • The body’s first line of defense against pathogen entry includes skin, cerumen (earwax), tears, mucus, saliva, stomach acid, and expulsive reflexes.
  • Phagocytosis and inflammatory responses are examples of the second line of defense.
  • Innate immune responses occur more quickly and before adaptive immune responses.
  • Phagocytosis is a type of endocytosis in which a cell engulfs a foreign particle and forms a vesicle around it called a phagosome that fuses with enzyme-filled lysosomes that break apart the potential pathogen.
  • Interferon can be produced by virally infected cells to help eliminate the virus. This interferon can also help recruit NK cells.
  • Inflammation is an innate immune response to injury that involves swelling, heat, and the action of phagocytes.
  • Unregulated inflammation can lead to chronic inflammatory diseases.

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