The Deep-Dive Series: How Our Immune System Works

Understanding how our body fights off infections is generally accompanied by a deeper sense of appreciation for all that our body does- and is constantly doing- to protect us.

Being exposed to even a few thousand infectious bacteria can make us sick. Really infectious diseases need an even lower number. Yet, we’re constantly exposed to microbes that could potentially make us sick. An average 5-inch cell phone is believed to have over 600,000 bacterial cells on its surface. A single sneeze can disperse 1,00,000 bacteria into the air, where they can survive for up to 45 minutes. Yoga mats can have millions of bacteria growing on them, depending on how they’ve been used. The examples could go on.

So why aren’t we sick all the time?

We owe this to the complex arrangement of structures, organs and cells that comprise our immune system, which unceasingly works on keeping us healthy.

They can be broadly classified into two groups: the innate immune system comprises the components that provide the first line of defence against infection, while our adaptive immune system is made up of specialised cells that are tailor-made to fight specific antigens (a broad term that describes both microbes and foreign, potentially harmful molecules).

Let’s delve a bit deeper into both.

The Innate Immune System

All individuals have a similar innate immunity. It’s hardwired into our genes and exists before our body is exposed to a pathogen, protecting us from a variety of potential pathogens (as compared to any specific ones).

This is made up of physical and physiological barriers, along with specialised cells. Specifically –

1) Anatomic barriers

These are mechanical barriers that physically prevent the entry of microbes.

Our skin is constantly exposed to the external environment, but has evolved in a way that prevents microbes from entering into its deeper layers. The outermost layer, the epidermis, consists of dead cells containing keratin in a tightly packed structure, that doesn’t allow microbes to pass through. The acidic pH of our sebum, produced by the sebaceous glands in the dermis i.e., the skin’s deeper layer, plays its part by preventing the growth of certain microbes.

Similarly, the mucous secreted by our mucous membranes, such as the inner lining of our digestive system and our nostrils, traps harmful organisms. Mucous membranes also have other defence mechanisms like producing tears in our eyes and saliva in our mouth, both of which have antibacterial and antiviral properties.

2) Physiologic barriers

Many of the things that our body does as part of its normal functioning confer protection against some pathogens.

When we eat, the acid released by our stomach a very low pH, which kills most of the microbes in our food. Our body temperature (~37⁰C) prevents the growth of microbes that tolerate only low temperatures, while fever, our body’s response to infection, can inhibit the growth of certain other pathogens.

3) Specialised cells

Our body has a range of cells that are specialised to function as an immediate response to foreign pathogens.

For example, cells such as macrophages, which are components of our blood, move through our body in a non-specific manner, cleaning up cellular debris and microorganisms that come in its path. They essentially engulf and ‘eat’ microbes through a process called phagocytosis.

Other specialised cells include mast cells, neutrophils (which are similar to macrophages) and dendritic cells (which serve as the link between the innate and adaptive immune systems; more details later).

4) Inflammatory response

Any cellular damage, whether a paper cut, a bruise or an infection, leads to an inflammatory response. This mainly involves increasing the blood flow to the site of damage, bringing with it proteins that fight microbes and the specialised cells mentioned previously.

Although our innate immunity offers a robust first line of defense against infections, many pathogens still make their way through.

That’s where our adaptive immunity comes into play.

The Adaptive Immune System

Unlike our innate immune system, which is present and active at all times, our adaptive immunity kicks in only when it’s exposed to an antigen. It then fights with a high degree of specificity, in that its response is tailormade for that specific antigen.

It does so largely via the response of two types of cells: B cells and T cells.

1) B Cells

These are a subset of white blood cells produced in the bone marrow. They mature in the bone marrow, developing antibodies in the process, which bind to the membranes of a B cell’s surface.

Antibodies are proteins that have a high affinity for a single, specific antigen. When an antibody encounters the antigen it has an affinity for, it binds to it and prevents it from causing our body any harm.

This specificity to a single antigen is possible due to a fascinating mechanism. Our genes have the ability to rearrange themselves within B-cells and produce an array of permutations that can potentially recognise over a billion different antigens.

Naïve B cells are B cells with a specific membrane-bound antibody that haven’t been exposed to an antigen. When a naïve B cell encounters an antigen it recognises (through the specific antibody on its membrane), it triggers an immune response, known as a ‘Humoral Immunity’.

In this response, naïve B cells begin to differentiate into two different cell types: plasma cells and memory B cells.

Plasma cells begin to secrete the antibodies (that were present on the naïve B cell’s surface), which bind to the potentially harmful antigen and prevent it from causing an infection. A single plasma cell can secrete more than 2000 molecules of antibody per second!

Memory B cells retain their membrane-bound antibody, and essentially store a ‘memory’ of the antigen that it just encountered, to help trigger a stronger response the next it recognises the same antigen.

They’re responsible for keeping us immune to a particular disease over time, and are the reason vaccines work.

2) T Cells

T cells are also created in the bone marrow, but don’t mature there. They migrate to the thymus (a gland behind the sternum, between the lungs) for their maturation, during which they develop T-cell receptors (TCRs) on their surface. Their TCRs allow them to bind to antigens and fight them off.

Unlike B cells, T cells cannot recognise antigens on their own. They need to have the antigens “presented” to them with the help of antigen-presenting cells (APCs).

All cells have proteins known as MHC molecules on their surface. General cells contain class 1 MHC molecules, whereas specialised cells of our immune system (like macrophages and dendritic cells, covered earlier) have class 2 MHC molecules.

After a specialised cell of our innate immune system breaks down an antigen into tiny parts (during phagocytosis), one of these parts is taken to and binds to its class 2 MHC molecule.

On the other hand, when a general cell is infected by an antigen, a part of the antigen is bound to its class 1 MHC molecule.

Any cell that has an antigen in its MHC molecule thus becomes an antigen-presenting cell (APC).

How a T cell now responds to the antigen, when presented by an APC, depends on the type of T cell it is. There are two types: T helper cells (Th) and Cytotoxic T cells (Tc).

T helper cells (Th) are activated by antigens that are bound to class 2 MHC molecules. When activated, Th cells begin secreting various proteins known as cytokines, which play an important role in activating B cells, Cytotoxic T cells (Tc), macrophages and various other cells that participate in the immune response.

Tc cells, when activated by cytokines, recognise any antigens bound to a class 1 MHC molecule, which indicates that the general cell in question has been infected by the antigen. It then proceeds to eliminate any cells that have been infected, such as in virus-infected cells or tumour cells.

The immune response by T cells and APCs is known as the ‘cell-mediated response’, as the presence of these cell types is essential for the response to take place. Humoral immunity, in contrast, can be provided just through antibodies. For example, antibodies from an immune individual can be transferred to confer immunity to the same pathogen in someone who has not yet been exposed to it (see the snake example given below).

Here are certain situations that illustrate the complex and effective manner in which our immune system works.

Vaccines

Vaccines are pathogens that are inactive, and so trigger an adaptive immune response without the risk of an infection.

Our body responds to vaccines by triggering an immune reaction, which is normally accompanied by a mild fever.

B-cells then form plasma cells, which begin to secrete antibodies, and memory B cells confer long-term immunity to the same pathogen.

The common cold

After a few days of exposure to one of the many viruses that cause the common cold (e.g. Rhinoviruses), symptoms begin to show. The virus enters our body and takes hold in the mucous membranes of our sinuses or throat.

Our innate immunity kicks in, which mounts an inflammatory response that leads to the symptoms of the common cold – sore throat, runny nose, congestion and a fever.

In a few days, the adaptive immune response takes over and clears the infection.

Allergies

Allergies occur when our body mounts an adaptive immune response to a foreign particle that isn’t necessarily harmful.

Pollen, for example, can be highly allergenic to certain individuals. This is because the previous exposure to pollen was recognised as a foreign particle by their adaptive immune system, which led to the formation of antibodies.

Every time the individual is subsequently exposed to pollen, memory B cells kick into high gear and mount an immune response to the same.

Snake bites

Snake venom can be highly toxic to our nerves and/or our blood cells, depending on the snake.
Bites from poisonous snakes are treated with an ‘anti-venom’ – a passive, humoral response that protects the victim.

To make this anti-venom, small, non-toxic doses of venom are injected into animals (generally horses), which begin to produce antibodies to the venom. These antibodies are removed from the horse and purified.

This is then injected into a victim, to neutralise the venom in their body.

References:

1. Immunology, Fifth Edition, Richard A. Goldsby, Thomas J. Kindt, Barbara A.Osborne, Janis Kuby.
2. Hara-Kudo Y, Takatori K, Epidemiology and Infection 2011.
3. Williams, Annual Review of Microbiology, 1960.
4. https://www.sciencealert.com/bacteria-in-your-coughs-and-sneezes-can-stay-alive-in-the-air-for-up-to-45-minutes
5. http://abc13.com/health/whats-living-on-your-yoga-mat/520032/