The second line of defense comes into play when a pathogen has penetrated the surface barriers and entered the body. Second line defenses attempt to limit the spread of pathogens through the body by taking a multifaceted approach to pathogen elimination. Although these innate internal defenses are fast-acting, they are nonspecific and provide only a kind of crude protection against any and all pathogens that enter the body. Think of them as being like the guards inside the castle. There are five lines of innate internal defense. One line of innate internal defense consists of the phagocytic cells, primarily the neutrophils and macrophages. A second set of cells, the natural killer (or NK) cells, kill body cells that have turned traitor by becoming either virus-infected or cancerous. Another line of defense does not involve cells at all, but rather antimicrobial proteins such as complement and interferons. The last two lines of defense are neither cells nor proteins, but processes. They are inflammation and fever. Sometimes the innate defenses are no match for invading pathogens, just as a massive invasion can overwhelm the guards on a castle wall. In this case, the armies of the adaptive defenses must be called out. Having already met the enemy, the innate defenses can influence the kind of response the adaptive immune system makes by passing chemical messages to the adaptive immune system, rather like this guard gesturing to his friends. This process is one of the many ways in which the innate and adaptive defenses work together. Pathogens that enter the body are often rapidly ingested by phagocytes, this process begins when a phagocyte recognizes and binds a pathogen. You might wonder how the phagocyte knows that something is a pathogen and not part of the body. Phagocytes use special cell membrane receptors, such as the mannose receptor and the Toll-like receptors (or TLRs), to recognize and bind molecules that are found only on certain pathogens, particularly bacteria, and not on normal body cells. At least 10 different Toll-like receptors have been identified on human phagocytes, each binding to a different pathogen molecule. When phagocytes recognize a pathogen, two events are triggered. The first is the ingestion of the pathogen. The second is the release of chemical alarm signals that mobilize other cells of innate and adaptive immunity. Let’s observe a phagocyte bind pathogens. Pathogens and the immune system are involved in an evolutionary arms race. Many pathogens have evolved strategies to avoid being killed by phagocytes. Let’s watch the macrophage try to destroy each type of bacterium (encapsulated and unencapsulated). Now let’s try the other kind. One strategy certain bacteria have evolved is to enclose themselves in a capsule that makes it more difficult for phagocytes to grab them. In response, the immune system has evolved molecules that can coat these bacteria and provide “hand-holds” that allow the phagocytes to bind and engulf these bacteria. This process of coating bacteria to enhance phagocytosis is called opsonization. Two immune molecules that can act as opsonins are antibodies and complement. We will learn more about both of these later, but here we will focus on antibodies. Observe a bacterium as it is coated with antibody. Phagocytes have receptors that attach to the opsonins. The opsonins form a link binding together the pathogen and the phagocyte, triggering phagocytosis. There are several other strategies that pathogens have evolved to escape destruction by phagocytes. These include secreting molecules that block the fusion of lysosomes with the phagosome, developing resistance to the effects of lysosomal enzymes and reactive oxygen intermediates, and finding ways to escape the phagosome, take up residence, and replicate within the cytoplasm of the phagocyte. The bacterium that causes tuberculosis is known for its ability to hide out and replicate inside macrophages. In response to bacterial strategies such as those already mentioned, the immune system has evolved a counter-strategy. Certain T cells of the more sophisticated adaptive defense mechanisms can enhance the entire killing process within the macrophage. This enhancement only happens when the macrophage presents antigen from such bacteria to the T cell. The interaction between T cells and phagocytes is another example of the interaction between innate and adaptive defense systems. Let’s watch the macrophage try to destroy the tuberculosis bacterium. Now we’ll enhance the macrophage’s killing ability by bringing the T cell to it. Natural Killer (NK) cells are unusual, in that they are a type of lymphocyte, and yet they are involved in innate immunity. They make up 10-15% of the lymphocytes circulating in the blood. Let’s compare these unusual lymphocytes to B and T cells. Like T cells, NK cells kill the body’s own cells under two circumstances— if those cells have been invaded by intracellular pathogens, or if they have become cancerous. NK cells also attack transplanted tissues, playing a role in the rejection of transplanted organs. NK cells are larger than B and T cells, and contain granules in their cytoplasm. Thus, NK cells are sometimes called “large granular lymphocytes”. While B and T cells express specific receptors for antigen, no such receptors are found on NK cells. Yet, NK cells can recognize a variety of cells as abnormal, bind to them and kill them. Now let’s learn how the NK cells recognize abnormal cells. Abnormal cells, such as cancerous cells or those infected by viruses, often reduce the expression of certain membrane proteins. The suppressed proteins are those that tell the immune system that a given cell is “self,” in other words that it belongs to the body. NK cells look for the absence of these “self” proteins. It’s as if NK cells were saying, “If I can’t identify you as one of us, then you are a traitor, and I will kill you.” Let’s watch the NK guard identify the traitor. NK cells and T cells are the two kinds of cells that continually scan our cells for abnormalities, a process called immune surveillance. They act in complementary fashion. T cells look for the presence of abnormal antigens on the cell surface, while NK cells look for the absence of normally occurring self-proteins. How do NK cells kill abnormal cells? The same way that cells called cytotoxic T cells kill— a process we will explore in detail later. For now, let’s just say that killing involves direct contact and induces the target cell to undergo apoptosis, which is programmed cell death or cellular suicide. NK cells are important in the early response to pathogens, acting to contain pathogens before the adaptive immune responses can take over. They continue to play a role after B and T cells are activated. Like macrophages, NK cells become more effective killers following activation by cytokines from certain T cells. Likewise, coating cells with antibody makes them better targets for killing by NK cells, just as coating pathogens with antibodies make them better targets for phagocytes. These processes show of how innate and adaptive host defenses work together to protect us from infections. The first set of antimicrobial proteins we will consider are the interferons. Interferons are members of a larger group of chemicals called cytokines that modulate the immune system. Interferons interfere with viral replication, modulate inflammation, and activate immune cells. The 3 types of interferon— alpha, beta, and gamma—are distinct proteins, but have common as well as unique functions. Gamma interferons act in a variety of ways to signal other immune and non-immune cells, and we will consider later. Here, we will learn about the anti-viral properties of alpha and beta interferons. Let’s begin by examining how viruses replicate within cells. Recall that viruses must enter cells to replicate. This is because a virus is little more than a protein-covered packet of nucleic acids— the genetic instructions for how to create a new virus. When a virus penetrates the target cell's membrane, it releases its nucleic acid and takes over the host cell’s machinery to make more copies of that virus. The presence of a virus replicating inside it causes the cell to produce and secrete interferons. Interferons bind to plasma membrane receptors on nearby cells. They act as warning signals for as-yet-uninfected cells, telling them that there is a virus on the loose. In response, the uninfected cells produce proteins that inhibit viral replication. These proteins act by degrading viral RNA and by preventing the synthesis of viral proteins. Let’s see how this process works. Now let’s see if a virus can reproduce itself when it tries to enter a cell, that has been alerted by interferon. Chewing up viral RNA and blocking protein synthesis are non-specific, in that they work against any virus. In the short term, these mechanisms protect uninfected cells not only against the virus that invaded its neighbor, but also against any other viruses that may be in the area. The next set of antimicrobial proteins we will consider is the complement system. Complement gets its name from the fact that it complements or enhances other components of both innate and adaptive defenses. Like the blood clotting cascade, complement is actually a complex cascade of interdependent plasma proteins. As each protein is activated, it becomes an enzyme that activates the next protein until the final product is formed. When activated, these proteins can mark cells for phagocytosis, promote inflammation, and even kill some bacteria all by themselves. Now let’s watch what happens when complement proteins enter this bacterium and see how it is lysed by the end-products of the complement cascade.
Table of contents
- 1. Introduction to Anatomy & Physiology5h 40m
- What is Anatomy & Physiology?20m
- Levels of Organization13m
- Variation in Anatomy & Physiology12m
- Introduction to Organ Systems27m
- Homeostasis9m
- Feedback Loops11m
- Feedback Loops: Negative Feedback19m
- Feedback Loops: Positive Feedback11m
- Anatomical Position7m
- Introduction to Directional Terms3m
- Directional Terms: Up and Down9m
- Directional Terms: Front and Back6m
- Directional Terms: Body Sides12m
- Directional Terms: Limbs6m
- Directional Terms: Depth Within the Body4m
- Introduction to Anatomical Terms for Body Regions3m
- Anatomical Terms for the Head and Neck8m
- Anatomical Terms for the Front of the Trunk8m
- Anatomical Terms for the Back9m
- Anatomical Terms for the Arm and Hand9m
- Anatomical Terms for the Leg and Foot15m
- Review- Using Anatomical Terms and Directions12m
- Abdominopelvic Quadrants and Regions19m
- Anatomical Planes & Sections17m
- Organization of the Body: Body Cavities13m
- Organization of the Body: Serous Membranes14m
- Organization of the Body: Serous Membrane Locations8m
- Organization of the Body: Thoracic Cavity8m
- Organization of the Body: Abdominopelvic Cavity12m
- 2. Cell Chemistry & Cell Components12h 37m
- Atoms- Smallest Unit of Matter57m
- Isotopes39m
- Introduction to Chemical Bonding19m
- Covalent Bonds40m
- Noncovalent Bonds5m
- Ionic Bonding37m
- Hydrogen Bonding19m
- Introduction to Water7m
- Properties of Water- Cohesion and Adhesion7m
- Properties of Water- Density8m
- Properties of Water- Thermal14m
- Properties of Water- The Universal Solvent17m
- Acids and Bases12m
- pH Scale21m
- Carbon8m
- Functional Groups9m
- Introduction to Biomolecules2m
- Monomers & Polymers11m
- Carbohydrates23m
- Proteins25m
- Nucleic Acids34m
- Lipids28m
- Microscopes10m
- Prokaryotic & Eukaryotic Cells26m
- Introduction to Eukaryotic Organelles16m
- Endomembrane System: Protein Secretion34m
- Endomembrane System: Digestive Organelles15m
- Mitochondria & Chloroplasts21m
- Endosymbiotic Theory10m
- Introduction to the Cytoskeleton10m
- Cell Junctions8m
- Biological Membranes10m
- Types of Membrane Proteins7m
- Concentration Gradients and Diffusion9m
- Introduction to Membrane Transport14m
- Passive vs. Active Transport13m
- Osmosis33m
- Simple and Facilitated Diffusion17m
- Active Transport30m
- Endocytosis and Exocytosis15m
- 3. Energy & Cell Processes10h 7m
- Introduction to Energy15m
- Laws of Thermodynamics15m
- Chemical Reactions9m
- ATP20m
- Enzymes14m
- Enzyme Activation Energy9m
- Enzyme Binding Factors9m
- Enzyme Inhibition10m
- Introduction to Metabolism8m
- Redox Reactions15m
- Introduction to Cellular Respiration22m
- Types of Phosphorylation11m
- Glycolysis19m
- Pyruvate Oxidation8m
- Krebs Cycle16m
- Electron Transport Chain14m
- Chemiosmosis7m
- Review of Aerobic Cellular Respiration19m
- Fermentation & Anaerobic Respiration23m
- Introduction to Cell Division22m
- Organization of DNA in the Cell17m
- Introduction to the Cell Cycle7m
- Interphase18m
- Phases of Mitosis48m
- Cytokinesis16m
- Cell Cycle Regulation18m
- Review of the Cell Cycle7m
- Cancer13m
- Introduction to DNA Replication22m
- DNA Repair7m
- Central Dogma7m
- Introduction to Transcription20m
- Steps of Transcription19m
- Genetic Code25m
- Introduction to Translation30m
- Steps of Translation23m
- Post-Translational Modification6m
- 4. Tissues & Histology10h 3m
- Introduction to Tissues & Histology16m
- Introduction to Epithelial Tissue24m
- Characteristics of Epithelial Tissue37m
- Structural Naming of Epithelial Tissue19m
- Simple Epithelial Tissues1h 2m
- Stratified Epithelial Tissues55m
- Identifying Types of Epithelial Tissue32m
- Glandular Epithelial Tissue26m
- Introduction to Connective Tissue36m
- Classes of Connective Tissue8m
- Introduction to Connective Tissue Proper40m
- Connective Tissue Proper: Loose Connective Tissue56m
- Connective Tissue Proper: Dense Connective Tissue49m
- Specialized Connective Tissue: Cartilage44m
- Specialized Connective Tissue: Bone12m
- Specialized Connective Tissue: Blood9m
- Introduction to Muscle Tissue7m
- Types of Muscle Tissue45m
- Introduction to Nervous Tissue8m
- Nervous Tissue: The Neuron8m
- 5. Integumentary System2h 20m
- 6. Bones & Skeletal Tissue2h 16m
- An Introduction to Bone and Skeletal Tissue18m
- Gross Anatomy of Bone: Compact and Spongy Bone7m
- Gross Anatomy of Bone: Periosteum and Endosteum11m
- Gross Anatomy of Bone: Bone Marrow8m
- Gross Anatomy of Bone: Short, Flat, and Irregular Bones5m
- Gross Anatomy of Bones - Structure of a Long Bone23m
- Microscopic Anatomy of Bones - Bone Matrix9m
- Microscopic Anatomy of Bones - Bone Cells25m
- Microscopic Anatomy of Bones - The Osteon17m
- Microscopic Anatomy of Bones - Trabeculae9m
- 7. The Skeletal System2h 35m
- 8. Joints2h 17m
- 9. Muscle Tissue2h 33m
- 10. Muscles1h 11m
- 11. Nervous Tissue and Nervous System1h 35m
- 12. The Central Nervous System1h 6m
- 13. The Peripheral Nervous System1h 26m
- Introduction to the Peripheral Nervous System5m
- Organization of Sensory Pathways16m
- Introduction to Sensory Receptors5m
- Sensory Receptor Classification by Modality6m
- Sensory Receptor Classification by Location8m
- Proprioceptors7m
- Adaptation of Sensory Receptors8m
- Introduction to Reflex Arcs13m
- Reflex Arcs15m
- 14. The Autonomic Nervous System1h 38m
- 15. The Special Senses2h 41m
- 16. The Endocrine System2h 48m
- 17. The Blood1h 22m
- 18. The Heart1h 42m
- 19. The Blood Vessels3h 35m
- 20. The Lymphatic System3h 16m
- 21. The Immune System14h 37m
- Introduction to the Immune System10m
- Introduction to Innate Immunity17m
- Introduction to First-Line Defenses5m
- Physical Barriers in First-Line Defenses: Skin13m
- Physical Barriers in First-Line Defenses: Mucous Membrane9m
- First-Line Defenses: Chemical Barriers24m
- First-Line Defenses: Normal Microbiota7m
- Introduction to Cells of the Immune System15m
- Cells of the Immune System: Granulocytes28m
- Cells of the Immune System: Agranulocytes26m
- Introduction to Cell Communication5m
- Cell Communication: Surface Receptors & Adhesion Molecules16m
- Cell Communication: Cytokines27m
- Pattern Recognition Receptors (PRRs)48m
- Introduction to the Complement System24m
- Activation Pathways of the Complement System23m
- Effects of the Complement System23m
- Review of the Complement System13m
- Phagocytosis17m
- Introduction to Inflammation18m
- Steps of the Inflammatory Response28m
- Fever8m
- Interferon Response25m
- Review Map of Innate Immunity
- Introduction to Adaptive Immunity32m
- Antigens12m
- Introduction to T Lymphocytes38m
- Major Histocompatibility Complex Molecules20m
- Activation of T Lymphocytes21m
- Functions of T Lymphocytes25m
- Review of Cytotoxic vs Helper T Cells13m
- Introduction to B Lymphocytes27m
- Antibodies14m
- Classes of Antibodies35m
- Outcomes of Antibody Binding to Antigen15m
- T Dependent & T Independent Antigens21m
- Clonal Selection20m
- Antibody Class Switching17m
- Affinity Maturation14m
- Primary and Secondary Response of Adaptive Immunity21m
- Immune Tolerance28m
- Regulatory T Cells10m
- Natural Killer Cells16m
- Review of Adaptive Immunity25m
- 22. The Respiratory System3h 20m
- 23. The Digestive System2h 5m
- 24. Metabolism and Nutrition4h 0m
- Essential Amino Acids5m
- Lipid Vitamins19m
- Cellular Respiration: Redox Reactions15m
- Introduction to Cellular Respiration22m
- Cellular Respiration: Types of Phosphorylation14m
- Cellular Respiration: Glycolysis19m
- Cellular Respiration: Pyruvate Oxidation8m
- Cellular Respiration: Krebs Cycle16m
- Cellular Respiration: Electron Transport Chain14m
- Cellular Respiration: Chemiosmosis7m
- Review of Aerobic Cellular Respiration18m
- Fermentation & Anaerobic Respiration23m
- Gluconeogenesis16m
- Fatty Acid Oxidation20m
- Amino Acid Oxidation17m
- 25. The Urinary System2h 39m
- 26. Fluid and Electrolyte Balance, Acid Base Balance Coming soon
- 27. The Reproductive System2h 5m
- 28. Human Development1h 21m
- 29. Heredity Coming soon
21. The Immune System
First-Line Defenses: Chemical Barriers
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