Innate immune system: Everything You wanted to Know About It

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The innate immune system is the natural immune system of the body. This is the inborn defense mechanism that is genetically determined. This arm of the immune system is divided into the barrier function and the cellular/protein defense function.

A. The barrier Function of the Innate immune system

Before your underlying cells and tissues can be accessed, there lie several barriers that are in the interface between your tissues and the outside world. If these barriers work well, then we cannot have entry and hence no infection.

The natural barriers are classified into biological, chemical, physical, and physiological barriers. We shall now discuss how each of them prevents the entry of pathogens into the body.

1. Physical Barriers

The physical barriers provide mechanical protection owing to their large surface area that covers the body making an interface with the outside world. They include:

The skin

The skin covers nearly all tissues. Your skin’s outer layer is made up of dead cells, which are renewed from time to time. If there were any microorganisms that had adhered to the dead cells they would be removed in the process.

Mucous membranes

Mucous membranes line all your hollow systems including the gastrointestinal system, urinary tract system, and respiratory system. The mucus membranes make an interface with the external environment. The epithelial layer’s tight junctions of these membranes make it difficult for microorganisms to penetrate.

Mucosal barrier of the innate immune system
Structure of the Mucosal Barrier of innate immune system (Source: Deposit Photos)

The Cilia

These structures are very important in the respiratory system. They propel microorganisms towards the outside making it difficult to adhere to the cells.

2. Chemical Barriers

The physical barriers can be classified into two:

Micro-environmental factors

An example of this is the level of pH. Some microorganisms cannot survive in acidic environments like in the vagina where the pH is around 4.4 and in the gastric mucosa where the pH is 1.3.

Antimicrobial molecules

We have several antimicrobial molecules that can directly destroy the pathogens when they attempt to attack. These include:


Some cells of the innate immune system like macrophages and neutrophils have Defensins. Defensins are proteins that can damage pathogens directly.


You may have these enzymes in your saliva, tears, sweat, and urine. Lysozymes kill bacteria by cleaving them, which damages their cell walls.  

Immunoglobulin A (IgA)

Naturally, IgA can be isolated in your tears, mucus, and saliva. This immunoglobulin can bind and neutralize microorganisms or mark them for destruction by phagocytic cells.


The mucous membranes produce mucus. Mucus traps the microorganisms and prevents them from adhering to the epithelial cells. The rapid movement of the mucus by the mucociliary escalator in the respiratory system minimizes the exposure time and hence prevention from adherence. In the gut, the fast movement of mucus through peristalsis prevents the adherence of microorganisms.


Besides lysozymes, other enzymes including endopeptidase can help your body kill pathogens. This happens through proteolysis which makes the pathogen lose important protein building blocks.

3. Biological Barriers as Part Innate Immune System

The most important biological barrier is the normal flora. These non-pathogenic microorganisms are found in the gut, skin, throat, mouth, vagina, and nasopharynx area. Normal flora prevents pathogenic microorganisms from causing disease by outcompeting them for some essentials. Such essentials include attachment sites and nutrition among others.

Some normal flora produces antimicrobial chemicals that can kill or inhibit the growth of microbes. You are discouraged from careless use of antibiotics because they may interfere with the integrity of your body’s normal flora. This will leave you vulnerable to pathogenic microbes.

Normal flora are an important part of the innate immune system
Normal flora bacteria which form an important part of biological barriers of the innate immune system (Source: Deposit Photos)

Examples of normal flora include Staphylococcus aureus in your nose, pseudomonas spp in your outer ears, Lactobacillus in the stomach, and Enterococci in your small intestines, Escherichia coli in your large intestines, and candida spp on the skin.

4. Physiological Barriers

These are the body’s responses to infection. They include diarrhea, vomiting, sneezing, and coughing. The responses are meant to expel the pathogens from the body before they can enter the blood or cells of your body.

Therefore, though all these responses carry some level of discomfort, we should be excited to have the responses because they can avert an infection.

B. Cellular/protein defense function of Innate Immune System

If a microbe crosses all the barriers that we have discussed above, the microbe would still be unlucky. It will be dealt with by cells of your innate immune system in a ruthless manner.

Recognition of Antigens by Innate immune cells

The innate immune cells possess on the surface of their plasma membrane some receptors. These receptors are called pattern recognition receptors (PRRs). The PRRs are receptors with broad specificity and are encoded in the germline (Genetically acquired).

The PRRs attach to microbe structures that appear as patterns. Those structures are called Pathogen Associated Molecular Patterns (PAMPs). Therefore, we can say recognition has happened when PRRs of your innate cells have bound PAMPs of the attacking microbe. Nearly all microorganisms have PAMPs on their surface.

Examples of PRRs include the Toll-like receptors (TLRs), and Nod-like receptors (NLRs). Others are extracellular PRRs for example the C-reactive protein (CRP) and the mannose-binding lectin (MBL). It is only after the recognition that the various effector mechanisms meant to eliminate the microbe can set in.

Effector Function of the Innate Immune Cells

An immune response can only be helpful to your body if it ends up with an effector mechanism that clears a microbe. The main effector function of the cells of the immune cells is phagocytosis. Others include inflammation and complement activation.

1. Phagocytosis

This process is important because several cell types of the innate immune system are involved including neutrophils, eosinophils, basophils, macrophages, and dendritic cells. After specific binding following recognition of the antigen, these cells engulf (Swallow) the microorganisms (Antigens).

Further, the process (Chewing catalytically) the antigens for presentation. Then these antigens can be presented to T cells if the cells phagocytosing are antigen-presenting cells.

2. Inflammation

This is an important effector arm of the innate immune system. When you are infected or have an injury in your tissues, the immune system embarks on recruiting immune cells to the site of infection. The endothelium of your blood vessels creates spaces between them for immune cells to exit (Process called extravasation).

The cells of the immune system using some surface receptors (integrins) attach to the endothelial cells and finally leave the blood vessels. They are then guided by some proteins called chemokines (A process called chemotaxis) to the exact place of infection.

At this point, each cell does what it is specialized for. Neutrophils will phagocytose the microorganisms killing them instantly. The macrophages will phagocytose bacteria, process them and present them as peptides to T cells.

During this process, the vascular permeability that makes it possible is marked by what are called cardinal signs of inflammation including redness, heat, swelling, and pain. Inflammation should be acute are resolve quickly after the elimination of microorganisms. However, it can sometimes be chronic leading to the death of cells and hence loss of their function.

3. Complement Activation

This is another important natural defense mechanism of your body. Your blood has about 30 proteins that are encoded in the germline (Heritable). When there is an infection the complement system is activated. The complement system can be activated through one of the three pathways namely:

a) Classical pathway – Initiated through Antigen-Antibody complex

b) Mannan-binding Lectin (MBL) pathway – Initiated by mannose on microbes

c) Alternative pathway – Begins by spontaneous hydrolysis of C3

The effector components of the complement system include the membrane attack complex (MAC) which lyses the microbes. Others are C3a and C5a which are mediators of inflammation and C3b which is an opsonin that makes phagocytosis of microbes easier.

Membrane attack complex is an important component of innate immune systemof
The complement system’s MAC is important in innate immune system

4. Antibody-dependent Cell Cytotoxicity (ADCC)

This effector function is not purely an innate function because of the involvement of the antibodies which are products of the adaptive immune system. But it is considered partly innate because the main players are natural killer cells (NK cells) which are innate cells.

Antibodies are attached to the antigens that provoked their production. Then the antibody-bound antigens are easily removed by NK cells by unleashing their toxic granules.

NK cells have special receptors that they use to recognize the Fc regions of the IgG antibodies that are attached to the microbes. Other cells that can be involved in ADCC include neutrophils, eosinophils, and macrophages.

The Innate Immune System is the Inborn Defense Mechanism

The rigidity of the receptors: The pattern recognition receptors (PRRs) can only recognize antigens with pathogen-associated molecular patterns (PAMPs). They are not flexible meaning that they only maintain the receptors encoded in the germline – inherited

Speed of response: The rapid action of the immune cells on innate immunity shows that they are ever ready which means that they are genetically determined.

Antigen Presentation: Innate immune cells present peptides to cells of adaptive immunity. The professional antigen presenters are macrophages and dendritic cells both of which are cells of the innate immune system


The innate immune system forms an integral part of our first-line defense mechanism against microbes. It is a natural mechanism but also links to the acquired immune system in many ways. This makes it easy for our bodies to fight antigens and remain safe.

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