Immunology 101 PDF

PROPRIETARY. DO NOT SHARE. Transcript: Immunology 101 Section 1: Immune System Welcome In this course, we will discuss the immune system, how it functions to prevent disease, and the basics of how these functions are used in biotechnology. This course is broken into 3 sections. The first section gi...

PROPRIETARY. DO NOT SHARE. Transcript: Immunology 101 Section 1: Immune System Welcome In this course, we will discuss the immune system, how it functions to prevent disease, and the basics of how these functions are used in biotechnology. This course is broken into 3 sections. The first section gives an overview of the immune system. The second section discusses the basics of disease so that we can then discuss how the immune system attacks diseases. The third section looks at the basic components of the immune system. Section 1: Immune System Objective Section 1 will start the course with a basic overview of the immune system. In this section, we have four objectives: • The first is to simply define the terms immunology and immunity to ensure that we are all on the same page. • The next is to list all of the tissues of the immune system and explain their functions. • Next, we will describe the key functions of the immune system. • Finally, we will discuss the relationship between the immune system and the biotechnology industry. Immunology Let’s begin by defining immunology. Immunology is the study of the systems and mechanisms an organism uses to protect itself. How do we get to an immune system? It all starts - as always in biotech! - with the DNA, with genes. There are specific genes that code for the different components of the immune system, namely proteins. Here we show an antibody, a classic protein used by the immune system to protect the body. But there are many other immune proteins as well which also have their genes. Then we have immune cells, such as macrophages, B-cell, T-cells, and many more that we will learn about in the coming sections. Of course, cells determine which genes are expressed, which in turn determines which 1 Copyright 2023 Biotech Primer, Inc. PROPRIETARY. DO NOT SHARE. proteins are expressed. And then there are immune-specific tissues, such as lymph nodes, that play a major role in your immune response. We will discuss the tissues of the immune system over the next few sections. Tissues of the Immune System Let’s look at the major tissues of the immune system. As you can see, the tissues of your immune system are scattered throughout your body. Bone Marrow Perhaps, the most important tissue, known as the primary immune tissue, is your bone marrow. Your bone marrow is where all of your immune cells originate from or “stem from.” All immune cells begin as stem cells and then differentiate - change or mature - into more specific cells with specific functions. Some of these immune cells, such as macrophages, neutrophils, and B-cells differentiate or mature in the bone marrow. Other immune cells will migrate out of the bone marrow and differentiate in other tissues. Thymus The Thymus is located behind your sternum, between your lungs. It is only active until puberty and after puberty, it slowly shrinks. By the age of 75, the thymus has been replaced with fatty tissue. Fortunately, the thymus has produced all your T-cells by the time you’ve reached puberty. So as mentioned, the T-cells originate in the bone marrow as stem cells, but then they leave the bone marrow and migrate to the thymus where they get chemical messages to differentiate or mature to become T-cells. The chemical message is thymosin, a hormone secreted by the thymus, which stimulates the development of T-cells. Lymph Nodes Lymph nodes are scattered throughout your body, and they are reservoirs for millions of B- cells, and T-cells. Their job is to nourish and maintain immune cells. It is also where certain cells of the immune system, specifically B-cells and T-cells, become activated. We will learn more about this 2 Copyright 2023 Biotech Primer, Inc. PROPRIETARY. DO NOT SHARE. activation process and what that means later in the course. For now, it is enough to know that lymph nodes are crucial to fighting disease. Spleen The spleen is the largest organ in the lymph system. It is an important organ, but you could live without it. The spleen is located under the rib cage and above the stomach. Adult spleens are usually 5 inches wide. The Spleen plays multiple supporting roles in the body: • It acts as a blood filter. • It controls the volume of red blood cells. • It fights infection- this is where the WBC is stored. Immunity Immunity consists of the mechanisms used by an organism to protect itself against external and internal agents that are potentially harmful. External agents are non-self, meaning our body did not produce these cells. Non-self agents include viruses, bacteria, fungi, and parasites. All come from our environment, enter our body, and have the ability to cause disease. Internal agents are self, meaning our body did produce these cells. The classic agent that our body produces is cancer, and as we all are well aware, cancer causes disease. Immune System Function: External Pathogens The immune system evolved to protect us from disease-causing organisms which are known as pathogens. Here we list groups of pathogens from the smallest to the largest, from microscopic viruses to large, multicellular parasites. Immune System Function: Internal Disease Our immune system may also protect us from internal diseases such as cancer. Your immune cells actually can detect and destroy cancer cells before you even know that they’re present. 3 Copyright 2023 Biotech Primer, Inc. PROPRIETARY. DO NOT SHARE. Because cancer cells originate within our bodies, however, the immune system does not always recognize them as a threat. The Immune System Is Universal Every living organism has some form of the immune system, even bacteria. There are two types of immune systems, the non-specific immune system which is always active and attacks all invaders in the same way, and the specific immune system which is activated and is targeted to a specific invader. We will discuss these two types of immune systems more later in this course, and full details of them will be discussed in our second Immune System course. For now, it is enough to know that these types of immune systems exist. Immunology & Biopharma The Biopharma industry uses the knowledge gained from the study of immunology to make immune-based products for research, diagnostic, and therapeutic purposes. Examples of products include antibodies used in research, home pregnancy kits that incorporate antibodies for diagnostic purposes, and vaccines used as therapeutics. So there are a wide variety of products that can be developed once we understand how the immune system works. Section 1: Immune System Overview Summary To summarize section 1: • We first defined immunology as the study of the systems and mechanisms an organism uses to protect itself. • We then defined immunity as all of the mechanisms used by an organism to protect itself against external and internal agents that are potentially harmful. • We then discussed the tissues of the immune system including the bone marrow, thymus, lymph nodes, and spleen. The bone marrow is where your immune cells “stem from” and where your B cells mature; the thymus is where your T-cells mature; the lymph nodes are where your B-cells and T-cells become activated, and your spleen acts as a trash can and disposes of all your dead immune cells and pathogens. • We next describe the key function of the immune system; to protect from both nonself and self-agents that cause disease. 4 Copyright 2023 Biotech Primer, Inc. PROPRIETARY. DO NOT SHARE. • Finally, we explained that the biopharma industry uses the knowledge gained from the study of immunology to make products. These products can be used for research, they can be used as diagnostic, or therapeutic purposes. 5 Copyright 2023 Biotech Primer, Inc. PROPRIETARY. DO NOT SHARE. Section 2: Disease Welcome In section 2, we will delve a little deeper into the concept of disease and learn how the disease is caused. Section 2: Disease Objectives In this section: • We will first define the word disease. • Having defined disease, we will then list the broad categories of disease. • Lastly, we will define pathogens, and give some examples of common pathogens and the diseases associated with them. Disease A disease is a specific disorder causing abnormal function within an organism. It is characterized by a recognizable set of signs and symptoms that can be directly traced or linked to an infection, to heredity, to diet, or to your environment. When the organism is out of balance, we say that you have a disease. To restore that balance, we must find a way to eliminate or neutralize the disease. Hopefully, if it’s a disease caused by a pathogen, your immune system does this all on its own. If not, sometimes we need to step in with something like antibiotics or biologics -- some kind of external help to get you through. Pathogen & Pathogenic A pathogen is derived from the Greek word “pathos” which means suffering. A pathogen is any non-self agent capable of causing disease. An agent is something that causes infection or disease, especially a microbe, such as a bacterium or a virus. Pathogenic simply means capable of causing disease. Sneezes protect your body by clearing the nose of bacteria and viruses, but of course, those bacteria and viruses are spread when you sneeze so it is entirely possible that you could infect a bystander with a pathogen from your sneeze. 6 Copyright 2023 Biotech Primer, Inc. PROPRIETARY. DO NOT SHARE. Broad Categories of Disease The disease is either communicable or non-communicable. Communicable diseases can be transmitted or communicated via an agent that is passed on from one individual to another. Or disease can be non-communicable, which means the disease is not caused by an agent and cannot be passed on. Our broad categories of disease are deficiency disease, hereditary disease, physiological disease, and pathogenic disease. As you can see all diseases are non-communicable except for pathogenic disease and it is this type of disease that your immune system is optimized to eliminate. Because of this, we will not discuss the first three disease types, deficiency diseases, hereditary diseases, or physiological diseases. Instead, we will focus on pathogenic diseases, the pathogens that cause these diseases, and how the immune system combats these diseases. Categories: Pathogenic Disease Pathogenic disease is caused by an infectious agent such as a virus, bacteria, fungi, or parasite. The pathogenic disease is communicable- it can be passed from one individual to another. Description of Pathogens Let’s pause here and take a closer look at pathogens and the human diseases with which they are associated. First are viruses, non-living particles that reproduce by taking over living cells. Common examples of diseases associated with viruses are the common cold, flu, herpes, measles, HIV, and chickenpox. Next is bacteria, a single-celled organism without a nucleus. Common examples of diseases associated with bacteria are strep throat, tuberculosis, food poisoning, and pneumonia. Then there are fungi (or the singular form fungus), the simple organism that grows as single cells or thread-like filaments. Common examples of diseases associated with fungi are Ringworm, athlete's foot, tineas, and candidiasis. Lastly, there are parasites, organisms that live in or on another organism and derive nutrients at the host’s expense. Common examples of diseases associated with fungi are Malaria, “traveler's diarrhea”, giardiasis, sleeping sickness, and hookworms. 7 Copyright 2023 Biotech Primer, Inc. PROPRIETARY. DO NOT SHARE. Section 2: Disease Summary To summarize this section: • We first defined disease as a specific disorder causing abnormal function within an organism characterized by a recognizable set of signs and symptoms that can be directly traced or linked to infection, heredity, diet, or the environment. • We then introduced two broad categories of disease. The first are communicable diseases, which are diseases that are passed from one organism to another, and the second are non-communicable diseases, which are diseases that cannot be passed on. In this course, we focus only on communicable diseases known as pathogenic diseases because those are the types of diseases that will be combated by the immune system. • Lastly, we defined a pathogen as any non-self agent capable of causing disease. Common pathogens are viruses, bacteria, fungi, and parasites. 8 Copyright 2023 Biotech Primer, Inc. PROPRIETARY. DO NOT SHARE. Section 3: Components of The Immune System Now that we have learned which organs make up the immune system and the characteristics of pathogens, let’s take a closer look at the components that make up the immune system. Section 3: Components of The Immune System Objectives In this section: • We will first differentiate between the non-specific and specific immune systems. • Next, we will give an overview of the cells that make up the immune system. • Lastly, we will explain each immune system cell’s role in the immune response. Immune System Overview This chart shows the branches of the immune system. Overall, your immune system is divided into two major parts. On the left, we have the non-specific, which is also known as the innate immune system. The terms non-specific and innate are used interchangeably, but for this course, we will use the term non-specific to keep it simple. The non-specific immune response is the defense system with which you were born. It protects you against all pathogens. It involves barriers that keep harmful materials from entering your body. These barriers form the first line of defense in the immune response. On the right, we have the specific or adaptive immune system. Again, these two terms mean the same thing, of these two we will use the term specific throughout this course. The specific immune system recognizes specific pathogens. This side of your immune system knows the difference between smallpox and salmonella, which as you will see is imperative to keeping you healthy. These two systems communicate with and interact with each other as much as necessary to eliminate the disease. 9 Copyright 2023 Biotech Primer, Inc. PROPRIETARY. DO NOT SHARE. Phases of Complete Immune Response In this section, we give a high-level overview of the phases of the complete immune response and the relative time of each phase of the immune response. In Phase 1, between 0-4 hours, we get the non-induced, non-specific immune response. Another term for the immune response at this stage is performed defenses. We will discuss preformed defenses in more detail in the next section. At 4-96 hours, we have our Phase 2 response. Here the cells of the non-specific immune response are beginning to become activated- this is called an induced, non-specific response. So certain cells of the immune system are now coming into contact with the pathogen. They’re beginning to engulf or eat these invading pathogens. As your immune cells respond to the threat an inflammatory response is triggered. An inflammatory response is your body’s way of recruiting other immune cells to the site of the infection. Often in these 4-96 hours, your non-specific immune system has dealt with the pathogen and there’s no need to go escalate to Phase 3. However, if your body was unsuccessful in stopping the pathogen in phase 2, your specific immune response will kick in 96 hours after first being infected. Now, the cells of your specific immune system are activated and they create very specific molecules to eliminate the pathogen that has invaded. This phase takes anywhere from 5-10 days to become fully activated. Immune System Cells Cells of the immune system are classified or known as white blood cells often abbreviated WBCs. All blood cells are derived from stem cells in the bone marrow, and these stem cells are known as hematopoietic stem cells, abbreviated as HSCs for hematopoietic stem cells. Here we show an example. In your bone marrow, we have stem cells. After the HSCs receive different molecular signals, they differentiate into precursor cells which ultimately differentiate into mature immune cells - specialized cells of the immune system. This is a very complex process and it occurs through multiple steps. Let’s take a look at those steps in the next slide. 10 Copyright 2023 Biotech Primer, Inc. PROPRIETARY. DO NOT SHARE. Lineage All the cells in the immune system come from a single population of identical cells – hematopoietic stem cells. HSCs reside in the bone marrow where they divide to produce identical stem cells. Stem cells then become progenitor cells. A progenitor cell is a cell that, like a stem cell, tends to differentiate into a specific type of cell, but is already more specific than a stem cell. A progenitor cell will ultimately become committed to becoming any of the different types of immune cells. This pathway of the differentiation of hematopoietic stem cells into specific types of immune cells is known as a lineage. The individual steps as we go from a stem cell to the final adult cell, require many different molecular signals. Most of these molecular signals are known as growth factors or stimulating factors. These molecular signals turn off and on different genes that express different proteins which cause the cell to change or differentiate to become what it is supposed to be: an eosinophil, neutrophil, macrophage, dendritic cell, B-cell, T-cell, etc. Here, we have shown you a very simplified diagram of a lineage that does not show all the steps, nor all the immune cells, but does give you an idea of the concept. There are often 5 to 10 steps involved and the gene expression is changing constantly as the cell differentiates from a stem cell to a progenitor cell, terminating into an adult cell of the immune system. Key Immune Cell Roles In this section, we will briefly discuss the key immune cells and their roles. This is not an exhaustive list but it includes the most frequently occurring cells of the immune system and the cells that the biotechnology industry most often studies and uses in terms of trying to develop new products. Neutrophils are the most abundant immune cell circulating through your blood. They are nonspecific and their mission is to detect and engulf or eat pathogens. Eosinophils are also circulating through your blood in search of pathogens. They too are nonspecific and their mission is to secrete cytotoxins, toxic chemicals that kill pathogens. 11 Copyright 2023 Biotech Primer, Inc. PROPRIETARY. DO NOT SHARE. A macrophage is usually found inside your tissues, so different tissues have tissue-specific macrophages. There are lung-specific macrophages, brain-specific macrophages, and liverspecific macrophages, and their first mission is to detect a pathogen and destroy it. But in addition to that, it processes the pathogen, breaks it down, and then takes those pieces of the pathogen to the lymph nodes where it presents those pathogen pieces to the cells of the specific immune system, especially T-cells to activate them. Macrophages are the bridge between the specific immune system and the non-specific immune system. These play a very critical role in your overall immune response. We will explain the macrophage in great detail in our second course on the immune system. Dendritic cells act very similar to macrophages and there are many different types of dendritic cells. Dendritic cells play a key role in the memory aspect of immunology, and, therefore, they’re being studied heavily in terms of how to create longer-lasting vaccines. B-cells ultimately secrete antibodies. These are one type of cell that is in our specific immune system. There are different B-cells for each pathogen. B-cells are highly specific and they respond to a specific threat. T-cells are also specific and there are two main classes. There are helper T-cells, which create signaling molecules known as cytokines, and killer T-cells kill tumor cells and virally infected cells. We will cover each of these cells in greater detail in the coming sections and see how they all work together to keep us healthy. Section 3: Components of The Immune System Summary To summarize this section: • We first define the non-specific immune system and the specific immune system. The non-specific immune system is the defense system with which you were born; It protects you against all pathogens, and the specific immune system evolves in your body and recognizes specific pathogens. • We then discussed a few key immune system cells and their roles in the immune response: o Neutrophils, macrophages, and dendritic cells engulf pathogens. o 12 Macrophages and dendritic cells also activate T-cells. Copyright 2023 Biotech Primer, Inc. PROPRIETARY. DO NOT SHARE. o Eosinophils secrete cytotoxins – poisonous chemicals - to kill infected cells and pathogens. o B-cells secrete antibodies that flag the cell for destruction. o T-cells secrete molecular signals to activate the immune system and directly kill virally infected cells and tumor cells. 13 Copyright 2023 Biotech Primer, Inc.