To Learn Immunology Well: Section 1

  • Categories:Learn about the Vaccines
  • Origin:WeChat official account -- Quick View of Pharmacy
  • Time of issue:2021-01-29
  • Views:0

(Summary description)

To Learn Immunology Well: Section 1

(Summary description)

  • Categories:Learn about the Vaccines
  • Origin:WeChat official account -- Quick View of Pharmacy
  • Time of issue:2021-01-29
  • Views:0

▉ Introduction

The term immunity is derived from the Latin word "immunis" in Roman times, which originally meant "exemption from taxes" and was later extended to mean "exemption from epidemics". Immunology is the science of studying the immune responsiveness and methods of organisms to antigenic substances. More commonly, immunity is a physiological function of the body to recognize "self" and "non-self" antigens, form innate immune tolerance to "self" antigens, and produce rejection of "non-self" antigens. Normally, this physiological function is beneficial to the body and can have anti-infection, anti-tumor and other immune protective effects that maintain the physiological balance and stability of the body. However, under certain circumstances of immune dysfunction, it will also cause harmful reactions and results to the body, such as triggering hypersensitivity, autoimmune diseases, and tumors.


Figure 1: Immune system


The immune system is like a football team, and the process of its work is a teamwork involving many different players. These players can be divided roughly into two groups: those that are members of the innate immune system team and those that are part of the adaptive immune system. These two groups work together to provide a powerful defense against invaders. Therefore, when learning the immune system, we should look at it from a macroscopic and overall perspective, rather than just clinging to a certain component.

Imagine you're watching a football game on TV, and the camera is isolated on one player, say, the tight end. You see him run at full speed down the field, and then stop. It doesn't seem to make any sense. Later, however, you see the same play on the big screen, and now you understand. That tight end took two defenders with him down the field, leaving the running back uncovered to catch the pass and run for a touchdown. The immune system is a lot like a football team. It's a network of players who cooperate to get things done, and focusing on a single player doesn't make much sense. You need an overall view. (Tight end and running back are the positions of players in football games)


Figure 2: Football game


▉ Physical barriers

Our first line of defense against invaders consists of physical barriers, and to cause real trouble viruses, bacteria, parasites, and fungi must penetrate these shields. Although we tend to think of our skin as the main barrier, the area covered by our skin is only about 2 square meters. In contrast, the area covered by the mucous membranes that line our digestive, respiratory, and reproductive tracts measures about 400 square meters – an area about as big as two tennis courts. We can therefore intuitively feel that there is a large perimeter which must be defended.


▉ The innate immune system

Any invader that breaches the physical barrier of skin or mucosa is greeted by the innate immune system – our second line of defense. Immunologists call this system "innate" because it is a defense that all animals just naturally seem to have. Indeed, some of the weapons of the innate immune system have been around for more than 500 million years.

Imagine you are getting out of your hot tub, and as you step onto the deck, you get a large splinter in your big toe. On that splinter are many bacteria, and within a few hours you'll notice that the area around where the splinter entered is red and swollen. These are indications that your innate immune system has kicked in. Your tissues are home to roving bands of white blood cells that defend you against attack. To us, tissue looks pretty solid, but that's because we're so big. To a cell, tissue looks somewhat like a sponge with holes through which individual cells can move rather freely. One of the defender cells that is stationed in your tissues is the most famous innate immune system player of them all: the macrophage. If you are a bacterium, a macrophage is the last cell you want to meet after your ride on that splinter! Here is an electron micrograph showing a macrophage about to devour a bacterium.


Figure 3: A macrophage devouring a bacterium


You will notice that this macrophage isn't just waiting until it bumps into the bacterium purely by chance. No, this macrophage actually has sensed the presence of the bacterium and is reaching out a "foot" to grab it. But how does a macrophage know that a bacterium is out there? The answer is that macrophages have antennae (receptors) on their surface which are tuned to recognize "danger molecules" characteristic of common microbial invaders. For example, the membranes that surround bacteria are made up of certain fats and carbohydrates that normally are not found in the human body. Some of these foreign molecules represent "find me and eat me" signals for macrophages. And when macrophages detect danger molecules, they begin to crawl toward the microbe that is emitting these molecules.

When it encounters a bacterium, a macrophage first engulfs it in a pouch (vesicle) called a phagosome. The vesicle containing the bacterium is then taken inside the macrophage, where it fuses with another vesicle termed a lysosome. Lysosomes contain powerful chemicals and enzymes which can destroy bacteria. In fact, these agents are so destructive that they would kill the macrophage itself if they were released inside it. That's why they are confined within vesicles. Using this clever strategy, the macrophage can destroy an invader without "shooting itself in the foot." This whole process is called phagocytosis, and the following image shows how it happens.


Figure 4: Phagocytosis


Macrophages have been around for a very long time. In fact, the ingestion technique macrophages employ is simply a refinement of the strategy that amoebas use to feed themselves – and amoebas have roamed Earth for about 2.5 billion years. So why is this creature called a macrophage? "Macro," of course, means large – and a macrophage is a large cell. Phage comes from a Greek word meaning "to eat." Therefore, it can be seen from its name that a macrophage is a big eater. In fact, in addition to defending against invaders, the macrophage also functions as a garbage collector. It will eat almost anything. Immunologists can take advantage of this appetite by feeding macrophages iron filings. Then, using a small magnet, they can separate macrophages from other cells in a cell mixture.


Figure 5: Macrophage


Where do macrophages come from? Macrophages and all the other blood cells in your body are the descendants of self-renewingblood stem cells – the cells from which all the blood cells "stem." By self-renewing, I mean that when a stem cell grows and divides into two daughter cells, it does a "one for me, one for you" thing in which some of the daughter cells go back to being stem cells, and some of the daughters go on to become mature blood cells. This strategy of continual self-renewal insures that there will always be blood stem cells in reserve to carry on the process of making mature blood cells.


Figure 6: Schematic diagram of stem cell differentiation


As the daughters of blood stem cells mature, they must make choices that determine which type of blood cell they will become when they grow up. As you can imagine, these choices are not random, but are carefully controlled to make sure you have enough of each kind of blood cell. For example, some daughter cells become red blood cells, which capture oxygen in the lungs and transport it to all parts of the body. In fact, our stem cell "factories" must turn out more than two million new red blood cells each second to replace those lost due to normal wear and tear. Other descendants of a blood stem cell may become macrophages, neutrophils, or other types of "white" blood cells. And just as white wine really isn't white, these cells aren't white either. Actually they are colorless. Immunologists use the term "white" to indicate that they lack hemoglobin, and therefore are not red.

When the cells that can mature into macrophages first exit the bone marrow and enter the blood stream, they are called monocytes. All in all, you have about two billion of these cells circulating in your blood at any one time. This may seem a little creepy, but you can be very glad they are there. Without them, you'd be in deep trouble. Monocytes remain in the blood for an average of about three days. During this time they travel to the capillaries looking for a crack between the endothelial cells that line the inside of the capillaries. These endothelial cells are shaped like shingles, and by sticking a foot between them a monocyte can leave the blood, enter the tissues, and mature into a macrophage. Once in the tissues, most macrophages just hang out, do their garbage collecting thing, and wait for the body to get injured and infected with pathogens so they can do some real work.


Figure 7: Monocyte


When macrophages eat the bacteria on that splinter in your foot, they give off chemicals which increase the flow of blood to the vicinity of the wound. The buildup of blood in this area is what makes your toe red. Some of these chemicals also cause the cells that line the blood vessels to contract, making the capillaries exude fluid into the tissues. It is this fluid that causes the swelling of the wound. In addition, chemicals released by macrophages can stimulate nerves in the tissues that surround the splinter, sending pain signals to your brain to alert you that something isn't quite right in the area of your big toe.

During their battle with bacteria, macrophages produce and give off (secrete) proteins called cytokines. These are hormone-like messengers which facilitate communication between cells of the immune system. Some of these cytokines alert monocytes and other immune system cells traveling in nearby capillaries that the battle is on, and encourage these cells to exit the blood to help fight the rapidly multiplying bacteria. Pretty soon, you have a vigorous "inflammatory" response going on in your toe, as the innate immune system battles to eliminate the "invaders".


Figure 8: Cytokines



So here's the strategy: You have a large perimeter to defend, so you station sentinels (macrophages) to check for invaders. When these sentinels encounter the enemy, they send out signals (cytokines) that recruit more defenders to the site of the battle. The macrophages then do their best to hold off the invaders until reinforcements arrive. Because the innate response involves warriors such as macrophages, which are programmed to recognize many common invaders, your innate immune system usually responds so quickly that the battle is over in just a few days.

In addition to the professional phagocytes such as macrophages, which make it their business to eat invaders, there are other players on the innate team. For example, the complement proteins that can punch holes in bacteria, and natural killer cells which are able to destroy bacteria, parasites, virus-infected cells, and some cancer cells. We will talk more about the macrophage's innate system teammates in the later sections.


Figure 9: Complement and NK cells


▉ Summary

As the first section of the working principles of the immune system, this section briefly describes the working principle of the innate immune system, and the next section will provide an overview of the adaptive immune system. The series is based on How the Immune System Works, which tells the basic knowledge of the immune system in an approachable and storytelling tone. The book is not boring at all and it deepens our understanding of immunology. It is hoped that readers who have not learned about the immune system and are interested in immunology can easily learn some immunological knowledge like listening to stories!




Reference link:

Figure 1: Janeway's immunobiology

Figure 2:

Figure 3, 4, 6: How the Immune System Works

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Figure 9: and

Bibliography: How the Immune System Works


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Time of issue:2022-03-29 08:59:20

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