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Innate Immunity Overview & Mechanisms

Sujata Kumari, Paul Bautista
  • Author
    Sujata Kumari

    Sujata Kumari has taught College level Biology and Biotechnology to undergraduate students for over 7 years. She has a doctorate (PhD) degree in the field of biosciences from Jawaharlal Nehru Centre for Advanced Scientific Research and Masters degree in Biotechnology from Madurai Kamaraj University. She also has certification from Government of India endorsing her eligibility for lectureship in colleges and universities.

  • Instructor
    Paul Bautista
Understand what innate immunity is, and learn about inflammation, neutrophils, macrophages, complement proteins, natural killer cells, and eosinophils. Updated: 01/20/2022

Innate Immunity

The human body is in a constant fight with the ubiquitous enemies, infectious microbes and pathogenic organisms. Some of these may remain extracellular, extracting nutrients from living tissues, while others may invade and live within animal/human cells, replicating and surviving well. These invaders range from being helpful (e.g., E. coli in the intestines) to being major pathogens which can be fatal (e.g., HIV). In spite of all these threatening situations, the human body manages to remain disease free most of the time. This is because it is equipped with a defense system against these deadly organisms. The system by virtue of which the body recognizes and defends itself against foreign and harmful substances or organisms is called the immune system. The immune system recognizes and responds by trying to destroy pathogens through several mechanisms. The two broad categories of the immune system are: 1) the innate immune system and 2) the adaptive immune system.

The innate immune system or innate immunity is the first line of defense and acts immediately and rapidly upon exposure to the foreign bodies or antigens (antigens are anything that elicit immune response). The innate immune system is composed of defenses or barriers that can be activated immediately to limit the spread and pathogenicity of pathogens, thereby protecting the body against them. The innate immune system is structured with multi-layered barriers and defense mechanisms. The types and mechanisms of the innate immune system are tabulated below with examples:

Innate Immunity Examples
Physical/Anatomical Barriers
Skin, Mucous membrane, cilia, eyelashes, body hair Skin acts as a physical barrier and prevents the entry of microbes.
Cilia present in different structures of the respiratory system and beat in an upward direction to repel microorganisms that enter during breathing.
Secretions
Mucus, bile, gastric juice, tears, saliva, sweat Mucus coats the cell surfaces, making it difficult for microbes to bind to these cells.
Lysozyme, secreted in tears and by sweat glands, breaks the cell wall of bacteria.
Physiological Barriers
Body temperature, fever, acidic conditions Body temperature and fever retard the growth of many microbes.
The acidic environment of sweat inhibits microbial growth, and low pH gastric juices kill many ingested pathogens.
Innate Immune Cell Mediated Responses
Neutrophils, macrophages, natural killer cells, eosinophils Neutrophils and macrophages are phagocytes that ingest and kill the microbe.
Natural killer cells mainly kill infected self-cells and some tumor cells by releasing granule contents onto them.
Inflammatory response Inflammation is the process that deals with tissue damage and infection.
It induces a leakage of vascular fluid and an influx of phagocytic cells at the site of infection.
Complement system response The complement system involves a cascade of molecular events leading to enhanced phagocytosis and the killing of microbes.

Innate immunity is the natural or intrinsic defense system with which one is born. It is inherited and present since the time of the birth of an individual and does not undergo much changes throughout their life. Innate immunity does not have any memory. That means the immune system does not remember encounters with previous infections and there are not many changes in its reactivity upon subsequent infections. Also, innate immunity poses a non-specific response as it does not differentiate between antigens and responds similarly against all.

Inflammation

Inflammation is the body's response and process to fight against pathogens, toxins, and injuries. It is a process of healing wherein immune cells are sent to the site of injury in response to certain chemicals (inflammatory mediators) from tissues, microbes, or from other cells, including mast cells and macrophages. Mast cells are central to the inflammatory process and are considered important inflammatory cells, as they release histamine and other inflammatory mediators on stimulation. This triggers vascular changes such as blood vessel dilation (vasodilation) and increased permeability of the blood vessel. Endothelial cells lining the blood cells start presenting adhesion molecules on their cell surface to which immune cells bind and stick to the wall of blood vessels. Due to increased permeability of the blood vessels, these immune cells squeeze out between the endothelial cells to the injured site. Increased blood vessel permeability also causes the leakage of serum proteins and fluids with anti-microbial properties into the injured site, causing edema (fluid accumulation), which results in swelling. Vasodilation causes increased blood flow that results in redness and heat. Pain receptors give rise to pain at the site of tissue damage. Thus, histamine released by mast cells acts as a chemoattractant to attract immune cells to the damaged site and initiate the inflammatory process. There are five key signs of inflammation, namely:

Redness, Heat, Swelling, Pain, and Loss of Function

Neutrophils

Neutrophils are phagocytes (phagocytes are specialized cells that engulf other cells, microbes or cell debris), typically the first cells to arrive at the site of an infection, as numerous neutrophils keep circulating in the blood stream at any given time. Neutrophils are also called polymorpho-nuclear cells (PMNs) because of the multi-lobed nature of their nuclei, which are produced in the bone marrow. Neutrophils possess granules which are capable of killing microbes in their cytoplasm, and hence are known as granulocytes. These short-lived neutrophils comprise the majority of white blood cells. Neutrophils have several different types of surface receptors that recognize specific molecules or patterns present exclusively on microbes. Some surface receptors are chemoattractant receptors, for attraction of neutrophils towards the microbes. Thus, the main function of neutrophils is to patrol the body, looking for the invading microbes and to immediately respond to inflammation to phagocytose them.


Schematic representation of neutrophils containing multi-lobed nuclei, squeezing out of a blood vessel into the site of infection.

Neutrophils


Phagocytosis is the major mechanism by which microbes are removed from the body. It is a multistep process consisting of the following steps:

1. Movement of phagocytes towards pathogen

2. Attachment of pathogen to the phagocytes via surface receptors

3. Engulfing of pathogen through extension of cytoplasm and invagination of plasma membrane of neutrophils around it, resulting in the formation of phagosome

4. Fusion of lysosome with phagosome and formation of phagolysosome

5. Killing of pathogen and exocytosis (throwing out the digested cell material to the cell exterior)

Neutrophils are an important component of the innate immune system as they provide front line defense by responding first to the infection site and killing the microbes. The normal range of neutrophils is around 40-60% of the total white blood cell count. A higher level of neutrophils in the blood indicates an active microbial infection.

Macrophages

Macrophages are tissue-bound phagocytes, unlike neutrophils, which reside in the bloodstream. Macrophages are the part of the mononuclear phagocyte system derived from monocytes. The major function of macrophages is to phagocytize leftover microbes, cellular debris, and dead cells in the tissue; they're equivalent to a clean-up crew. Macrophages take different names while doing the same functions in different tissues; some of those names are:

  • Kupffer cells in the liver
  • Mesangial cells in the kidney
  • Microglial cells in the brain
  • Osteoclasts in the bone
  • Alveolar macrophages in the lungs


Schematic representation of macrophages phagocytizing pathogens. 1- Pathogens, a- Cytoplasm extension of macrophage, 2- Phagosome, 3- Lysosome, b- Lysosome fusing with phagosome, 4- Phagolysosome, c- Exocytosis

Macrophage and phagocytosis


Neutrophils and macrophages are called professional phagocytes, as these cells are not only capable of containing and killing the microbes by phagocytosis, but they also process them for antigen presentation, and they play an essential role in initiating the adaptive immune response. Although neutrophils and macrophages have similar functions, they differ in the following ways:

The Innate Immune System

When people think of the immune system, the first thing that comes to mind is often antibodies or vaccines or some other aspect of acquired immunity to an infectious agent that the body has already seen. But how does the body protect itself against potentially dangerous bacteria and viruses that it has never seen before? The immune system needs a way to quickly respond to a variety of unknown invaders, whether they've been encountered before or not, and all of the aspects of the immune system that respond to these unknown threats contribute to our bodies' innate immunity or the ability of the immune system to respond to unknown threats.

The innate immune system defends the body against malignant cells, viruses, and other invaders
Pathogens

The innate immune system is capable of mounting a defense against a variety of different threats, including malignant or cancerous cells, viruses that have already infected a cell, multicellular parasites and any other potential pathogens or foreign invaders that are capable of causing disease that might enter the body through an open wound or body orifice. So, let's take a look at how the innate immune system works.

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  • 1:16 Inflammation
  • 3:10 Neutrophils
  • 4:31 Marcrophages
  • 5:17 Complement
  • 7:00 Natural Killer Cells
  • 8:00 Eosinophils
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Inflammation

Let's say that our friend Phil is rock climbing when he cuts himself on a sharp edge. It's not a bad cut, so Phil ignores it, but his immune system certainly doesn't! As soon as Phil sustains even the smallest injury, the potential for infection by a foreign invader dramatically increases. In fact, even with the most minor cuts, thousands, if not millions, of foreign entities, most of them bacteria, will enter the wound. So, whenever there is an injury, it is in the body's best interest to mount an immediate immune response to destroy all foreign invaders before they can establish a foothold.

The first response of the body to a localized injury or infection is inflammation or the immediate response of the body to injury or infection that includes an influx of blood plasma and immune cells to a localized area. Injured tissues release a number of signaling molecules, which cause blood vessel dilation, increase blood vessel permeability, and causes endothelial cells that line the blood vessels to present adhesion molecules on their surface. These adhesion molecules are recognized by immune cells in the blood or white blood cells, which bind to the adhesion molecules and stick to the blood vessel wall. The white blood cells then squeeze themselves between endothelial cells of the now more permeable blood vessels and enter the tissue surrounding the vessel.

The signaling molecules are immune cell chemoattractants that cause the immune cells to exit the blood vessel and migrate to the site of injury. One of the best known inflammatory signaling molecules is histamine, which is capable of dilating blood vessels, increasing blood vessel permeability, and causing immune cells to exit the bloodstream and enter the damaged tissue.

Cardinal Signs:

There are five signs that describe an inflammatory response.

The Cardinal Signs of Inflammation

Neutrophils

The first immune cells that arrive at an injured site are mostly neutrophils, which are quick-response immune cells that recognize and destroy bacteria. Neutrophils are the most numerous type of white blood cell in the blood, and their job is to immediately respond to inflammation and kill bacteria by phagocytosis, which is the process by which a cell engulfs, destroys and digests another cell, bacteria or cellular debris.

Neutrophils are the first immune cells to arrive at an injured site
Neutrophils and phagocytosis

Neutrophils have several different types of receptors that recognize several different pathogen-associated molecular patterns that are specific to bacteria and not found on human cells. When the receptors bind to the bacteria-specific patterns, the neutrophil captures the bacteria and engulfs it, surrounding it with its plasma membrane. This intracellular compartment is called a phagosome because it is created during the process of phagocytosis. Lysosomes then fuse with the phagosome to add their digestive enzymes, which kill the bacteria and break it down into its component amino acids, nucleic acids and monosaccharides. These nutrients can then be used by the neutrophil or released into the tissue for use by other cells.

Macrophages

Macrophages are another type of immune cell that phagocytizes foreign organisms, dead cells and cellular debris. Macrophages are a little bigger than neutrophils. They live longer than neutrophils and stay in the tissue even after all of the pathogens are gone. They act like a clean-up crew that phagocytizes left over debris, bacteria and dead cells.

Complement

So far, most of the components of the innate immune system that we've talked about have been different types of cells, but there are non-cellular components of the innate immune system, too. Complement is a group of serum proteins which mark and destroy foreign microorganisms. Complement proteins are capable of forming a membrane attack complex on plasma membrane surfaces through a series of interactions between the different complement proteins. If the complement proteins are allowed to complete the membrane attack complex, it creates holes in the plasma membrane of its target and destroys it.

Complement proteins form a membrane attack complex on foreign microorganisms
Complement proteins

Complement proteins are very non-specific; they will attempt to form membrane attack complexes on any plasma membrane they can. Now this might cause a problem if complement proteins formed membrane attack complexes on the body's own cells and destroyed them, but our cells don't let this happen.

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Video Transcript

The Innate Immune System

When people think of the immune system, the first thing that comes to mind is often antibodies or vaccines or some other aspect of acquired immunity to an infectious agent that the body has already seen. But how does the body protect itself against potentially dangerous bacteria and viruses that it has never seen before? The immune system needs a way to quickly respond to a variety of unknown invaders, whether they've been encountered before or not, and all of the aspects of the immune system that respond to these unknown threats contribute to our bodies' innate immunity or the ability of the immune system to respond to unknown threats.

The innate immune system defends the body against malignant cells, viruses, and other invaders
Pathogens

The innate immune system is capable of mounting a defense against a variety of different threats, including malignant or cancerous cells, viruses that have already infected a cell, multicellular parasites and any other potential pathogens or foreign invaders that are capable of causing disease that might enter the body through an open wound or body orifice. So, let's take a look at how the innate immune system works.

Inflammation

Let's say that our friend Phil is rock climbing when he cuts himself on a sharp edge. It's not a bad cut, so Phil ignores it, but his immune system certainly doesn't! As soon as Phil sustains even the smallest injury, the potential for infection by a foreign invader dramatically increases. In fact, even with the most minor cuts, thousands, if not millions, of foreign entities, most of them bacteria, will enter the wound. So, whenever there is an injury, it is in the body's best interest to mount an immediate immune response to destroy all foreign invaders before they can establish a foothold.

The first response of the body to a localized injury or infection is inflammation or the immediate response of the body to injury or infection that includes an influx of blood plasma and immune cells to a localized area. Injured tissues release a number of signaling molecules, which cause blood vessel dilation, increase blood vessel permeability, and causes endothelial cells that line the blood vessels to present adhesion molecules on their surface. These adhesion molecules are recognized by immune cells in the blood or white blood cells, which bind to the adhesion molecules and stick to the blood vessel wall. The white blood cells then squeeze themselves between endothelial cells of the now more permeable blood vessels and enter the tissue surrounding the vessel.

The signaling molecules are immune cell chemoattractants that cause the immune cells to exit the blood vessel and migrate to the site of injury. One of the best known inflammatory signaling molecules is histamine, which is capable of dilating blood vessels, increasing blood vessel permeability, and causing immune cells to exit the bloodstream and enter the damaged tissue.

Cardinal Signs:

There are five signs that describe an inflammatory response.

The Cardinal Signs of Inflammation

Neutrophils

The first immune cells that arrive at an injured site are mostly neutrophils, which are quick-response immune cells that recognize and destroy bacteria. Neutrophils are the most numerous type of white blood cell in the blood, and their job is to immediately respond to inflammation and kill bacteria by phagocytosis, which is the process by which a cell engulfs, destroys and digests another cell, bacteria or cellular debris.

Neutrophils are the first immune cells to arrive at an injured site
Neutrophils and phagocytosis

Neutrophils have several different types of receptors that recognize several different pathogen-associated molecular patterns that are specific to bacteria and not found on human cells. When the receptors bind to the bacteria-specific patterns, the neutrophil captures the bacteria and engulfs it, surrounding it with its plasma membrane. This intracellular compartment is called a phagosome because it is created during the process of phagocytosis. Lysosomes then fuse with the phagosome to add their digestive enzymes, which kill the bacteria and break it down into its component amino acids, nucleic acids and monosaccharides. These nutrients can then be used by the neutrophil or released into the tissue for use by other cells.

Macrophages

Macrophages are another type of immune cell that phagocytizes foreign organisms, dead cells and cellular debris. Macrophages are a little bigger than neutrophils. They live longer than neutrophils and stay in the tissue even after all of the pathogens are gone. They act like a clean-up crew that phagocytizes left over debris, bacteria and dead cells.

Complement

So far, most of the components of the innate immune system that we've talked about have been different types of cells, but there are non-cellular components of the innate immune system, too. Complement is a group of serum proteins which mark and destroy foreign microorganisms. Complement proteins are capable of forming a membrane attack complex on plasma membrane surfaces through a series of interactions between the different complement proteins. If the complement proteins are allowed to complete the membrane attack complex, it creates holes in the plasma membrane of its target and destroys it.

Complement proteins form a membrane attack complex on foreign microorganisms
Complement proteins

Complement proteins are very non-specific; they will attempt to form membrane attack complexes on any plasma membrane they can. Now this might cause a problem if complement proteins formed membrane attack complexes on the body's own cells and destroyed them, but our cells don't let this happen.

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Frequently Asked Questions

Are neutrophils part of the innate immune system or the adaptive immune system?

Neutrophils are a part of the innate immune system as they are the first cells to arrive and respond (phagocytize) at the infection site.

What is the difference between neutrophils and macrophages?

Neutrophils and macrophages both are immune cells and kill microbes by the phagocytosis process. Neutrophils are short-lived and found in the blood stream whereas macrophages are long-lived and tissue-bound phagocytes.

What type of cells cause inflammation?

Mast cells are central to the process of inflammation as they release histamines and other inflammatory mediators. These inflammatory mediators trigger vascular changes and thus initiate the inflammatory process.

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