LESSONS 5.1 & 5.2 WORKBOOK

Transcription

1 Macrophage Macrophage. LESSONS 5.1 & 5.2 WORKBOOK Our body s barriers the innate immune system In Unit 5 we are going to explore how the body responds to infection and how pathogens bypass these responses. In this lesson we will review the structures / barriers of the immune system that we learned in Unit 1. We will then focus on cellular responses to microbes that enter the sterile areas of the host. This discussion will begin by defining innate and adaptive immunity. Then we will focuses on how cells of the innate immune system recognize and respond to pathogens. These cells see the world as self and nonself with receptors that recognize structures in microbes that do not exist in humans. Once they recognize a nonself entity, innate immune cells respond by removing the threat and sounding the alarm. Most infections are stopped by these innate immune responses! Review the physical, chemical, and cellular barriers of the immune system. Before proceeding with a discussion about how immune responses work, we need to refresh our memory about the immune barriers that we discussed in Unit 1.5. Use your knowledge of these barriers to answer the questions to the right, but if you need to return to Unit 1.5 to refresh your memory. What do the physical barriers of the What do the chemical barriers of the What do the cellular barriers of the Lessons 5.1,2 1

2 Dendritic cell Innate respnses are the first line of defense. We are born with innate immunity encoded in our DNA. Innate responses provide general pathogen recognition, they are not pathogen specific. Adaptive responses add another line of defense when they are called into action by the cells of the innate immune system. Recognition by adaptive cells is learned rather than premade at birth and responses are tailored to fit specific pathogens. Immune responses are generally broken into two classes; innate and adaptive. Once a pathogen gains access to the sterile parts of the body, like the bloodstream, it will meet immune cells. These cells come in two main classes: innate and adaptive. As the names suggest, we are born with innate responses and they don t change in respond to different pathogens. Because they are pre-made they can respond quickly when a foreign entity is encountered. In contrast, adaptive responses need to learn to fit individual pathogens. This process takes time so adaptive responses are delayed when a pathogen is encountered for the first time, but the response is remembered so if the same pathogen is encountered again the response will be swift. There are numerous types of innate cells but only two types of adaptive cells. As we learned before, innate and adaptive immune cells are found in the sterile interior of the body. They are only called into play when a microbe breaches other immune barriers to gain access to the sterile interior. There are many types of innate cells but we will focus on the functions of the three most important: macrophages, dendritic cells, and neutrophils. All of these cells are specialized to remove pathogens by eating them (phagocytosis). They also call for help by releasing cytokines. The cytokines can stimulate or inhibit cells or in some cases they can physically attract them. When the cytokines attract other cells to the site of infection or host damage this is called chemotaxis. If innate cells are not able to control an infection they will activate adaptive immune cells. As mentioned above, there are only two types of adaptive cells: B cells and T cells. We all have a single B and T cell specific for every imaginable pathogen already, but one is not enough! in order to respond to an infection this single cell needs to multiply. Thus there is a delay after the pathogen has been recognized while the B and Lessons 5.1,2 T cells expand to generate a large enough army 2 to fight the invader. Can the receptors that innate cells use to recognize pathogens change to better recognize pathogens? Why are adaptive immune responses delayed?

3 Neutrophil Stem cell: is a cell that can divide into more stem cells or change (differentiate) into other cell types. Differentiation: is the process of a cell changing to become another cell type or subtype. For example, a stem cell can turn into a lymphocyte. All cells in the blood, including immune cells, are made in the bone marrow through a process called hematopoiesis Like most cells in the body, blood cells are constantly dying and being replaced (this is called turning over), and both innate and adaptive cells behave in the same way. All cells in the blood are generated from stem cells in the bone marrow. The stem cells can either divide, which keeps the number of stem cells constant, or they can acquire the specialized characteristics of all the cell types in the blood (this is called differentiation). Immune cells differentiate from stem cells in stages: First, a stem cell differentiates into a myeloid or lymphoid progenitor cells (it is not important to remember these specific names, but you should remember that the first stage does not produce fully mature cells). Then, these immature blood cells further differentiate. The immature myeloid progenitor cells become blood cells, platelets, and innate immune cells. The lymphocyte progenitor cells then become mature adaptive immune cells (either B or T cells). It is important to understand this process because combating infection often requires certain immune cells to expand considerably in number. As we will see later, this rapid expansion requires a considerable amount of energy. In fact, when a person has an infection their metabolic needs may increase by 1,000 calories a day. The rest of this unit focuses on the cellular responses to an infection. Macrophages, dendritic cells, and neutrophiles reside in the blood and tissues of the body, constantly patrolling for foreign invaders. They use their innate receptors to recognize these invaders. The picture on the right shows a neutrophil (yellow) attached to a foreign cell (pink). How are stem cells involved in hematopoiesis? How does cellular differentiation play a role in hematopoiesis? How might the process of hematopoiesis relate to the phrase: feed a cold? Lessons 5.1,2 3

4 Conserved: A structure or sequence that is unchanging or similar across species, cells, or microbes. Endosome: a compartment inside of a cell contained within a membrane. Chemokines: These molecules are a type of cytokines that are used to attract other cells by chemotaxis. Innate receptors see targets that are not found in the host To fight infection, immune cells need to be able to distinguish between a pathogen and a self cell. This ability to distinguish between self and non-self is the foundation of the immune response, and requires specific receptors that can recognize non-self molecules. This is why many pathogens adapt ways to camouflage them selves from immune cells. After all, if immune cells can t see the pathogen they won t respond. The receptors innate cells use to recognize pathogens are inherited and don t change, so they need to recognize parts of pathogens that are highly conserved. These targets of recognition are called Pathogen Associated Molecular Patterns (PAMP). As you can see in the slide to the right, most PAMPs are structures that are required for a pathogen s life cycle, so mutating the PAMP to try to avoid immune recognition is likely to put the pathogen at a selective disadvantage. Because of this the innate immune system can clear about 99% of all infections. However, if the pathogen does mutate, the innate receptors can t adapt in response, so the innate cells may become blind to the pathogen! After innate cells recognize a PAMP they neutralize the threat in two main ways: Phagocytosis and Chemotaxis Phagocytosis: When an innate cell recognizes a pathogen it will engulf it. Once inside, the innate cell digests (kills) the pathogen using an endosome that acts like the stomach of an innate cell. Chemotaxis: Innate cells also sound the alarm by releasing molicules (cytokines and chemokines) that recruit other immune cells. Cytokine release also increases blood flow at the site of infection causing swelling and heat (inflammation). For example, a mosquito bite becomes red and hot because innate cells move to the site. PAMPS that innate cells recognize are generally conserved structures. Why might this be the case? Define phagocytosis: Define chemotaxis: Lessons 5.1,2 Most infections stop here!!! 4

5 If innate responses can t clear an infection they will prime adaptive immune cells. Innate cells activate adaptive cells in three ways: One, they release cytokines that stimulate B and T cells. Two, they release chemokines to attract adaptive cells to the site of infection. Three, they display the peptides from the digested invader on their cell surface for patrolling T cells to see. These molecules are called PAMPS and the process of displaying them is called antigen presentation and it is required to activate T cells. Antigen presentation is shown in the figure above, and we will describe how antigen presentation occurs in subsequent lessons. Lessons 5.1,2 5