Macrophages, Cytokines, and Immunity

Estimated Reading Time: 7 minutes

Immunity is complicated. After centuries of research, scientists are still discovering new information about what makes it tick. It’s a complex network of cells, antibodies, organs, and more. Honestly, it would take YEARS to cover all the information in-depth. That’s why we’ll be taking it just a few pieces at a time. 

You might think this knowledge is only useful for medical professionals or biologists. But think again! Your everyday lifestyle choices play a major role in the health of your immune system even at the cellular level. Certain foods cause inflammation by influencing cytokine production, while supplements like Echinacea have a positive impact on cytokine production.

So, even if you’re not a scientist, this is valuable information! Read on and learn about macrophages, cytokines, and the important role they play in immunity. 

 

A Brief Overview of Your Immune System

We’ve said it before, but we’ll say it again. Your immune system is like a highly sophisticated security department. When your body is exposed to stimuli, your immune system performs a threat assessment and responds in a variety of ways. That stimulus could be allergens, injuries, germs from a sticky door handle, or even things like food or emotional distress.

In order to thoroughly analyze and respond to such a wide array of stimuli, your immune system needs a vast network of “security employees.” That could be white blood cells that help fight infections and diseases, the lymphatic system that helps remove cellular waste, or even the mucous lining in your digestive tract that contains antibodies. 

Honestly, that doesn’t even begin to cover the complexity of the immune system. So many different parts of your body are constantly working together to maintain energy, fight off infections, heal and recover, and more. Basically, your immune system is the unsung hero of health and wellness. It’s so good at keeping you healthy, you don’t even think about it until you have a weak immune system.

This brings us to macrophages (pronounced mak-ruh-feyj) and cytokines (pronounced sahy-tuh-kahyn). While all of the immune components we mentioned earlier are incredibly important, these little guys are constantly working at the cellular level to keep you safe and healthy. Plus, they play important roles in both innate and acquired immunity.

 

Innate Immunity

You’re born with this type of immunity (also known as long-term immunity). Think of this as your first line of defense against microbes. You possess this natural resistance against certain infections because of your genetics

 

Acquired Immunity

Also known as adaptive immunity, this is the resistance to various foreign substances you’ve acquired during the course of your life. Oftentimes, various activities of the innate immune system will trigger responses from your acquired immune system.

What Are Macrophages?

Macrophages are a type of white blood cell. It helps to think of them as the deadly super spies of the immune system—you’ll see what we mean by that in a moment.

These specialized cells are formed when your body has an infection or a buildup of damaged or dead cells. For example, imagine you have some type of infection. It could be something as simple as a scrape that wasn’t cleaned properly, or even a respiratory tract infection. In response to the infection, monocytes leave the bloodstream, become smaller macrophage cells, and then locate and enter the infected area. 

Once this transformation is complete, they’ll change again and again to form different structures that can fight whatever “enemy” they encounter (microbe, virus, etc.). Basically, they’ll use whatever alias is best to get close to and fight their enemy i.e. the infection. After they’ve identified the threat, macrophages do two things. They’ll engulf and consume these threats, and then alert other white blood cells about the potential invaders.

So, just like super spies, macrophages are great at swiftly eliminating enemies and sending relevant information back to headquarters. 

Macrophages, Innate Immunity, and Acquired Immunity

Their ability to share information with the rest of the immune system is particularly important when it comes to long-term immunity against pathogens. In this way, macrophages almost act as a link between your innate and acquired immune responses. 

Immunobiology says that innate immune system cells like macrophages, “…play a crucial part in the initiation and subsequent direction of adaptive immune responses, as well as participating in the removal of pathogens that have been targeted by an adaptive immune response.” Confused? Let’s break it down…

Innate immunity reacts immediately to general microbes, oftentimes releasing macrophages in the process. When a macrophage digests a microbe, it will actually change its appearance and display that microbe’s antigens on its surface. This acts as a “Wanted” sign that tells other white blood cells to look out for those specific microbes. After that, your immune system creates more white blood cells to assist in the immune response against that specific threat. 

However, macrophage lifespan can last anywhere from a few weeks to several months. So, a macrophage that’s adapted to a particular pathogen will continue alerting the rest of your immune system until it undergoes apoptosis (pronounced ap-uhp-toh-sis) or programmed cell death. Put more simply, your immune system will “remember” how to identify and respond to specific pathogens. Depending on how long that “memory” is, that response will become part of your acquired immunity.

That’s why, after catching and recovering from some viruses, your body remembers how to identify and respond to them. Depending on the virus, that protection could last a few months, years, or even your entire life. However, the duration and extent of that type of virus immunity depends on a number of different factors. That makes it difficult to determine how long that protection will last for different people.

What Are Cytokines?

Cytokines are a group of proteins and, according to the British Society for Immunology, their two main producers “are helper T cells (Th cells) and macrophages.” While their functions are vast, their main purpose is to act as chemical messengers to help regulate immune responses. You can think of them as the informants and coordinators for your “security department.” 

There are many different cytokines, so the list below is just a brief glimpse. Sometimes they act alone, together, and sometimes they can even work against each other.

 

Chemokines [ kē′mō-kīn′ ]

These cytokines call in other cells to an infection site (this process is called chemotaxis). Essentially, chemokines coordinate other cells before moving forward with an “attack.” 

 

Interferons [ in-ter-feer-on ]

These particular proteins make it more difficult for viruses to replicate. A cell that becomes infected with a virus will release interferons. That tells other cells to protect themselves against the virus. They also activate Natural Killer T Cells which destroy infected cells and make it even more difficult for a virus to spread.

 

Interleukins / (ˌɪntəˈluːkɪn) /

Interleukins are mainly produced by white blood cells and their purpose is to regulate immune and inflammatory responses. They signal to other white blood cells that it’s time to show up and get to work. Additionally, there are different kinds of interleukins with unique purposes within the immune system.

 

Lymphokines [ lim-fuh-kahyn ]

These proteins are produced by lymphocytes (white blood cells). Lymphokines can be produced by both T-cell and B-cell lymphocytes to attract even more immune cells in preparation for a response.

 

Tumor Necrosis Factor

This type of cytokine destroys cells, including cancer cells. TNFs can be produced by many cells, but they’re mainly created by macrophages. Once released, they can bind to cells and destroy them. 

Obviously, cytokines are a varied and complex bunch of proteins. Some cytokines increase inflammatory responses from the immune system (proinflammatory cytokines) and some decrease inflammatory responses (anti-inflammatory cytokines).

Macrophages, Cytokines, and the Inflammatory Response

Both macrophages and cytokines play important roles when it comes to inflammation. Let’s look at a normal inflammatory response to see precisely how macrophages and cytokines are involved. 

Very quickly after developing an infection, macrophages or other white blood cells will identify pathogens and alert the rest of your immune system that an inflammatory response is necessary. This often requires the secretion of cytokines by macrophages to get the word out faster. 

When this happens, you’ll likely experience swelling, heat, redness, and/or pain at the affected site. These are all indicative of changes in local blood vessels associated with an inflammatory response. 

The heat and redness are a result of increased vascular diameter which also slows blood flow. The swelling is usually a result of increased vascular permeability. While this can result in painful swelling, it also means plasma with various immune cells has an easier time accessing the affected area. Endothelial cells lining your blood vessels will also activate and express molecules that make it easier for white blood cells to bind wherever necessary. Additionally, microvessels clot near the affected area to prevent the spread of any pathogens.

This inflammatory response helps the body defend itself against microorganisms, creates a physical barrier preventing any infection from getting into the bloodstream, and it also promotes healing. Depending on the situation, various types of cytokines may be secreted. For example:

  • C5A (a protein fragment) boosts vascular permeability, helps the endothelium express adhesion molecules, and encourages local mast cells to release granules containing histamine and TNF
  • When macrophages identify a pathogen, they rapidly produce TNF because it’s really good at activating endothelial cells. That last part is necessary for the inflammatory response.
  • Like we said earlier, cells that become infected with a virus will release interferons to slow the spread of the virus. Macrophages may also release interferons if a larger response is needed.

Cytokines and Inflammatory Pain

But what happens when an inflammatory response is too aggressive? A cytokine storm is one example of an overactive inflammatory response. This happens when your immune system floods your body with proinflammatory cytokines in response to an infection. While the purpose of this is to aggressively destroy any pathogens, it can also destroy tissue and damage organs.  

While inflammation is a normal part of an immune response, those with autoimmune disorders may regularly experience cytokine storms or chronic inflammatory pain.

The Journal of Interferon and Cytokine Research says several human studies have illustrated how proinflammatory cytokines “contribute to the initiation and propagation of autoimmune inflammation, whereas anti-inflammatory cytokines facilitate the regression of inflammation and recovery from acute phase of the disease.”

While osteoarthritis (OA) isn’t considered an autoimmune disorder, cytokines play a part in the overall pain and inflammation those with OA experience. Mediators of Inflammation says that various cytokines are secreted during the progression of OA. They stress, however, that “The most important effect that cytokines have involves disturbing the catabolism and anabolism processes, particularly important in tissues that are often subject to high mechanical load, such as human joints.”

Need a breakdown? Anabolism and catabolism are metabolic processes that work synergistically together to accomplish things like producing energy or repairing cells. So, when cytokines disrupt these processes in joint tissues, it’s a problem. It leads to degeneration of cartilage, then inflammation, MORE degeneration, and eventually loss of joint function. All of this is pretty painful. 

If someone’s immune responses are healthy, cytokines won’t cause problems and macrophages resolve inflammation once the response is no longer needed. Unfortunately, while some disorders have effective treatments, scientists are still struggling to understand the precise mechanisms and triggers behind many autoimmune and inflammatory disorders.

How Can YOU Benefit From Macrophage & Cytokine Knowledge?

In the end, knowledge is necessary and you deserve to know what makes your immune system tick! We’re pretty obsessed with all things health and wellness, so be sure to subscribe to our newsletter for more updates on living better. Join the HakaLife Family and take charge of your health today.

 

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