A Primer on Immunology

Immunology Basics: Essential Information in the Time of COVID-19

Every day, news articles and headlines about COVID-19 include technical terms, such as antigens, cytokine storm, neutralizing antibodies, and memory cells. Though most people have not studied immunology in depth, a basic understanding of the immune system is now essential to navigating through the pandemic. This primer, and the next articles in our series Immunity and Vaccines, are intended to provide basic information to help you make informed decisions. Resources and references for more detailed information are listed at the end of each article.

What is the immune system?

The immune system acts to protect the body against harmful invaders, which include bacteria, viruses, fungi, parasites, and other microbes (together, these are called pathogens). The human body has many defenses to protect against these pathogens getting inside. Examples include:

Skin and corneas to act as a barrier to pathogens;
Mucus in the nose, mouth, eyes, and genitals to trap and kill pathogens;
Tears to wash away pathogens;
Stomach acid to kill pathogens that might be swallowed.

Still, pathogens sometimes make their way inside the body. The immune system, which is spread throughout the body, is constantly on alert for any pathogens that can cause illness.

There are four functions of the immune system:

Recognize pathogens in the body;
Mobilize its forces to defend against the pathogens;
Defend against the pathogens;
Keep the fight within limits so the body itself is not damaged, and end the fight when the pathogens are eliminated.

The immune system is made up of several types of white blood cells, tissues, and organs. White blood cells (also calledleukocytes) are cells that circulate throughout the body but do not carry oxygen or carbon dioxide. Instead, they keep watch for pathogens, and mount a defense against them.

Recognizing pathogens in the body

In order to recognize harmful invaders in the body, the immune system must figure out what should be in the body (“self”) and what should not be in the body (“non-self”). One key way that the immune system can tell “self” from “non-self” is by checking the body for substances produced by pathogens. These substances, called antigens, are not normally found in the body. They may be proteins, certain types of sugars, or fragments of genetic material, and they are “red flags” to the body that a pathogen is present.

First wave of defense: the innate immune system

The immune system defends against pathogens in two waves. The first wave is the innate immune system (also called innate immunity). The innate immune system is the front guard that is always watching and always ready to take action at the first sign of invasion. Certain types of white blood cells that are part of the innate immune system can act like sentries – they are constantly on the lookout for antigens throughout the body. When these white blood cells detect antigens, they will alert many other white blood cells. White blood cells communicate with each other using different types of protein molecules that act as chemical messengers in the body. These chemical messengers are called cytokines. There are many types of cytokines that can communicate a variety of messages.

As soon as the sentry white blood cells of the innate immune system send out the alert using cytokines, other white blood cells of the innate immune system swing into action. There are at least seven different types of white bloods cells that are part of the innate immune system. Here are some of the functions they can perform:

Directly killing pathogens by surrounding and engulfing them – literally “eating” the pathogens whole.
Releasing toxic chemicals that punch holes in the outer membrane of pathogens like bacteria and parasites.
Releasing cytokines that cause more white blood cells to rush to the site of the infection. A side effect of this rush is swelling, redness, and pain (called inflammation).
Killing “self” cells that have been damaged or infected by pathogens.

Second wave of defense: the adaptive immune system

The adaptive immune system (also called acquired immunity) is the second wave of defense. This part of the immune system reacts more slowly but is very strategic. The adaptive immune system can remember and learn from previous invasions, and respond much more effectively the next time it sees pathogens again. There are two types of white blood cells that are part of the adaptive immune system: T cells and B cells.

T cells specialize to take on a specific function. Among the functions of different types of T cells are:

Help kill any “self” cells that have become damaged or infected by pathogens. It is important that damaged “self” cells get killed quickly, before they can damage the healthy “self” cells around them. To do this, the specialized T cells usually work together with some types of innate immune system white blood cells.
Make and release cytokines, the chemical messengers of the immune system, into the bloodstream. These cytokine-producing T cells are very important for keeping all parts of the immune system coordinated, just like messengers in the army are vital to keeping the troops coordinated.

B cells also have several functions, but their main function is to make antibodies. Antibodies are Y-shaped protein molecules that bind to antigens. The antigens can be free-floating in the blood (such as botulinum toxin) or can be part of the pathogen itself (such as proteins that are on the outside of a virus).

When antibodies bind to antigens, different scenarios may play out. For example:

If antibodies bind to antigens that are free-floating in the blood, they may signal to nearby white blood cells that pathogens are in the area, ramping up the immune response in that area.
If antibodies bind to antigens that are on the surface of pathogens themselves, sometimes they may completely incapacitate the pathogen. These powerful antibodies are called neutralizing antibodies, because they neutralize the threatening pathogen immediately. The pathogen will later need to be killed and cleaned up by white blood cells, but the neutralizing antibodies attached to it render it totally helpless in the meantime. In effect, neutralizing antibodies wound the attacker so that it can no longer attack, and is simply waiting to be killed. Neutralizing antibodies can take the body many days to figure out how to make, but once accomplished, B cells will pump out up to 10,000 antibodies per cell per second.

Wrapping up the defense

Once both the first wave (innate immune system) and the second wave (adaptive immune system) work together to kill all of the pathogens in the body and to kill all of the damaged and infected “self” cells, it is time to wrap up the immune response. It is important to stand down, or white blood cells might unintentionally begin to kill healthy “self” cells. To start this process, some white blood cells release cytokines that send the message out that the defense was successful and is now over.

Some white blood cells that were activated will begin to shut down and die. They are no longer needed, and so the body clears them away. Because the body is always making new white blood cells, there will be always fresh reserves to replace those that shut down and die. The fresh reserve white blood cells have never yet been part of a defensive fight. There is little chance that they might accidentally hurt a healthy “self” cell. These fresh reserves of white blood cells will have their turn to become active the next time pathogens invade the body.

Wrapping up the immune response is a process that can go on for many months. Some white blood cells continue to make antibodies for months after the defense is over, in case the same pathogen invades again. These antibody levels will slowly become lower and lower over time.

Memory cells

Even though the immune system wraps up the defense, the immune system still learns and keeps a memory of many of the different types of pathogens that it encounters. Memory cells are the way that the immune system learns. Both B cells and T cells can become memory cells. These cells mainly live in the spleen, tonsils, lymph nodes, and bone marrow, although some of them circulate throughout the body as well. Memory cells live for many years, or in some cases a person’s entire lifetime, just waiting for their target pathogen to try to invade again.

The minute memory cells recognize their old foe, they mount a defense. Memory B cells start pumping out thousands and thousands of neutralizing antibodies per second. Memory T cells quickly begin to kill any damaged “self” cells, and they swiftly communicate to the entire immune system that a repeat invasion is underway. Often the memory B and memory T cells are so quick and so strong that the person never even knows they are fighting off a repeat invasion from a pathogen they killed before. They do not feel sick at all!

Memory cells can be produced at the tail end of a successfully fought-off invasion. They can also be produced after the immune system is exposed to vaccines. In future articles in this series, we will look at how vaccines can produce immune memory.

Cytokine storm

We have been describing an immune system response that proceeds normally and is well controlled. However, sometimes the immune system does not stay in control. Sometimes certain white blood cells release far too many cytokines (chemical messengers) that signal the immune system to attack. A cytokine storm happens when the immune system keeps ramping up and attacking harder and harder, to the point that the immune system is damaging healthy “self” cells. Sometimes, the immune system becomes so out of control that the person dies from it. Researchers still do not entirely understand why certain pathogens are more likely to cause a cytokine storm, and why certain people’s immune systems are more likely to have it happen.

— Jillian Lokere and Aliaa Barakat

Glossary

Adaptive immune system: The part of the immune system that reacts more slowly than the innate immune system but more specifically. The adaptive immune system is only activated when the innate immune system senses an attacking pathogen. The key players of the adaptive immune system are T cells and B cells.

Antibodies: Y-shaped protein molecules that bind to antigens.

Antigens: Any substances that the immune system recognizes as “non-self” and which cause the immune system to respond. These may be proteins, certain types of sugars, or fragments of genetic material that are caused by pathogens invading the body.

B cells: White blood cells in the adaptive immune system that make antibodies.

Cytokines: Small protein molecules that act as chemical messengers. White blood cells use cytokines to communicate with each other and with other parts of the immune system.

Inflammation: An innate immune system response in which blood and fluid is directed to the site of an infection or injury. This allows white bloods cells more access to the area. Side effects include redness, warmth, and swelling.

Innate immune system: The front guard of the immune system that is always watching and always ready to act at the first sign of invasion by pathogens. There are at least seven types of white blood cells that are part of the innate immune system. These cells can directly eliminate pathogens by engulfing them, release chemicals that punch holes in pathogens, kill “self” cells that are damaged or infected by pathogens, and release cytokines to cause other white blood cells to rush to the area where the pathogens are detected.

Leukocytes: Another name for white blood cells. White blood cells are part of the immune system, and they play a role in monitoring for pathogens and/or attacking pathogens.

Memory cells: These immune cells circulate throughout the body at low levels for many years, or in some cases a person’s entire lifetime, just waiting for their target pathogen to try to invade again. The minute memory cells recognize their old foe, they mount a defense. They provide long-term protection against pathogens that the body has fought off before.

Neutralizing antibodies: Antibodies that bind to antigens that are on the surface of pathogens themselves and which completely incapacitate the pathogens. Neutralizing antibodies wound the attacker so that it can no longer attack and is simply waiting to be killed by white blood cells.

Pathogens: Harmful bacteria, viruses, fungi, parasites, and other microbes that can cause illness.

T cells: White blood cells of the adaptive immune system. They help kill damaged or infected “self” cells, and they send cytokines (chemical messages) to other cells in the immune system.

References and further reading

Delves, PJ. Overview of the Immune System. Merck Manual Consumer Version [online]. Kenilworth, NJ: Merck & Co., Inc.; 2020.
George, A. Cytokine Storm. New Scientist [online].
U.S. National Library of Medicine. Medline Plus. Immune System and Disorders.