In the previous tutorial we began to discuss immune cells, and we did this by going over immune cell function in a general way. Now it’s time to get more specific about the different types of immune cells, and which of these functions is performed by each type. Most immune cells originate in the bone marrow and develop from hematopoietic stem cells, which also give rise to red blood cells and platelets. To become a white blood cell, a hematopoietic stem cell can follow one of two major differentiation tracks, those being the myeloid lineage and the lymphoid lineage. Hematopoietic stem cells develop through these lineages into fully developed immune cells by following specific sets of molecular cues in the bone marrow. Historically, many of these cells were characterized based on how they appeared under a microscope. However, we now have molecular tools to define cells based on the proteins they express on their surfaces, and thus based on which genes are turned on inside the cell. Let’s start with the myeloid-derived innate immune cells, which include macrophages, monocytes, granulocytes, and dendritic cells. As we’ve mentioned previously, macrophages are the professional eaters of the immune system. They are very good at killing pathogens by phagocytosis, the process by which a pathogen is engulfed and ingested. Macrophages are also important for keeping tissues free of cellular debris by phagocytosing dead and dying self cells. Macrophages that live in these tissues under normal conditions are called tissue-resident macrophages, and these cells originate in the fetal yolk sac, rather than the bone marrow. Almost every tissue has a specific type of tissue-resident macrophage which performs important maintenance roles during homeostasis. During inflammation, a process we will describe at length a bit later, cells can also enter tissues from the bloodstream as monocytes, which then differentiate into macrophages. Macrophages are also important for secreting cytokines that can shape the immune response. Next, we have a family of immune cells called granulocytes. This name comes from the fact that these cells are preloaded with granules full of antimicrobial chemicals that they can release during an infection to kill pathogens. Neutrophils, eosinophils, basophils, and mast cells are all types of granulocytes. Neutrophils, eosinophils, and basophils are also called polymorphonuclear leukocytes, or PMNs, because of the unique, multi-lobed shape of their nuclei that can be seen under a microscope. Neutrophils are the most numerous immune cell type in the blood, and the first type of immune cell to arrive on the scene when tissues become infected. They are extremely good at phagocytosis and killing pathogens, especially bacteria, but they have a very short lifespan compared to other types of white blood cells. These are also the cells which produce the pus that we can see during an infection. Eosinophils and basophils are much less common in the blood than neutrophils. Eosinophils release many cytokines and other chemical factors that are important for promoting wound healing and tissue repair. Basophils are the least common, but the largest type of granulocyte in the blood. These secrete cytokines and other signaling molecules. Mast cells are similar to basophils, but do not have a multi-lobed nucleus and are usually found in connective tissue instead of circulating in the bloodstream. Mast cells, eosinophils, and basophils are important for killing large parasites that are too big to be destroyed by phagocytosis. However, these cells are also responsible for promoting allergies and asthma. Next up, dendritic cells also are capable of phagocytosis, but unlike macrophages and the granulocytes, they aren’t usually heavily involved in pathogen clearance. Instead, dendritic cells patrol tissues for signs of infection so they can take antigens back to structures called lymph nodes, which we will discuss in the next tutorial, and activate T cells that will be able to specifically neutralize that kind of pathogen. In this way, dendritic cells are critical for linking the innate and adaptive immune systems. There are also innate immune cells that are derived from the lymphoid lineage, and these cells are called innate lymphoid cells. This group of cells includes natural killer cells, which recognize and kill cancer cells and virally infected cells. There are many other kinds of innate lymphoid cells, which sense microbial cues and stress signals, allowing them to quickly respond to a diverse range of microbial threats. Innate immune cells are effective at identifying and clearing different pathogens, but they can only recognize generalized features of pathogens, not specific ones, and they can’t differentiate between good and bad microbes. This is where adaptive immune cells come in. Adaptive immune cells also derive from the lymphoid lineage, and are called lymphocytes. First up are B cells. The main role of these is to make antibodies, which are incredibly specific Y-shaped proteins that can bind to, and coat pathogens and foreign particles. Antibody binding blocks pathogens from entering cells and marks them for destruction by phagocytes. However, B cells require help from T cells to become fully activated. There are 3 main types of T cells, and they are defined by their functional role, as well as their expression of identifying surface proteins, CD8 or CD4. Here, CD stands for cluster of differentiation, which is a designation that immunologists use to name various molecules that are expressed on the surface of immune cells. We will see a variety of CD numbers throughout this series. Killer T cells express CD8, and are able to very specifically identify and kill self cells that are cancerous or infected. Helper T cells express CD4 and are called “helper” cells because they are important for helping to activate B cells. They are also critical for secreting cytokines to guide the immune response, depending on the type of threat. Regulatory T cells also express CD4, and these cells secrete cytokines to tone down the strength of the immune response. They can even kill killer T cells if they start getting out of control. After encountering a certain pathogen once, T and B cells can live for years in the body, so the next time they see that pathogen, these cells are able to mount a faster and stronger reaction, allowing the body to control the infection more quickly. So to summarize, the immune system is made up of billions of myeloid-derived and lymphoid-derived white blood cells that circulate in the bloodstream and patrol tissues for signs of damage or infection. These cells communicate with each other through cytokines and chemokines to carry out their diverse array of effector functions which help destroy pathogens and heal damaged tissue. Once again, each of the cell types we’ve gone over here will get its own tutorial later in the series, but we have some work to do before we get there, so next up let’s investigate the lymphatic system.