Innate Immunity (Host Defense I) - Non-Specific Host Defenses - Summer 2020 PDF

Chapter 14 Innate Immunity (Host Defense I: Non-Specific Host Defenses) 3 parts to Immunity I. Nonspecific surface defenses – Structural, Mechanical, Biochemical II. Innate Immunity (Nonspecific) – Complement, Phagocytosis, Inflammation, Fever, and Viral specific defenses III. Adaptive Immunity...

Chapter 14 Innate Immunity (Host Defense I: Non-Specific Host Defenses) 3 parts to Immunity I. Nonspecific surface defenses – Structural, Mechanical, Biochemical II. Innate Immunity (Nonspecific) – Complement, Phagocytosis, Inflammation, Fever, and Viral specific defenses III. Adaptive Immunity (Specific) – Humoral immunity, Cellular immunity Summary of the major components of the host defenses. Fig. 14.1 Flowchart summarizing the major components of the host defenses. Firstline of defense • Barriers – Anatomical – Chemical – Genetic Representation of the primary anatomical and chemical defense barriers. Fig. 14.2 The primary physical and chemical defense barriers. Anatomical barriers • Skin – Outermost layer – Hair follicles – Skin glands • Mucous membrane – – – – Digestive Urinary Respiratory Eye I. Nonspecific surface defenses A. Structural 1. Epithelial surfaces, tight fit of cells is useful, first barrier against attack a. Keratinized skin- thick, strong, waterproof b. Mucous membranes – thinner, weaker but has mucous c. Sloughing of skin sheds microbes and nutrients quickly Figure 15.1 Surface of human skin (SEM) • The Role of Mucous Membranes in Innate Immunity – Mucous membranes line all body cavities open to environment – Two distinct layers • Epithelium – – – – Thin outer covering of the mucous membranes Epithelial cells are living Tightly packed to prevent entry of pathogens Continual shedding of cells carries away microorganisms • Deeper connective layer that supports the epithelium © 2012 Pearson Education Inc. B. Mechanical (actual physical removal) 1. Peristalsis keeps bacteria from settling, moves it along GI tract. 2. Mucociliary system – Mucus is produced to trap organisms and ciliary movement sweeps it up and out. 3. Body fluids mechanically removing microbes from surfaces, urine, tears etc. C. Biochemical (inhospitable environment) 1.Sebum/Fatty acids on skin 2. Sweat makes skin salty 3.Stomach secretions, HCl acid 4. Bile disrupts cell envelope 5. Lysozyme in all skin secretions breaks down peptidoglycan (gram +, or gram - ?) Chemical barriers • • • • Sebaceous secretions Eyelid glands – meibomian gland Tears and saliva – lysozyme Acidic pH – – – – – Sweat Stomach Skin Semen Vagina Genetic barriers • Different level of sensitivity and resistance to infectious agents – Malaria – Tuberculosis – Leprosy – Fungal infections If the pathogen gets past all of that, then the second layer of defenses, Innate Immunity, comes into play Immunology • Study of the development of resistance to infectious agents by the body – Surveillance of the body – Recognition of foreign material – Destruction of foreign material or agent • Involve nonspecific and specific immune defense systems • White blood cells (wbc) or leukocytes are involved WBC do not destroy self cells, while nonself cells are recognized and destroyed. Fig. 14.4 Search, recognize,and destroy is the mandate of the immune system. Systems • All systems are integrated – Recticuloendothelial system (RES) – Extracellular fluids system (ECF) – Blood or circulatory – Lymphatic The integration of the systems enable the recognition and destruction of foreign particles in the human body. Fig. 14.5 Connection between the body compartments. Reticuloendothelial (RES) • Network of connective tissue fibers (Reticulum) • Interconnects cells • Allows immune cells to bind and move outside the blood and lymphatic system Extracellular fluid (ECF) • The spaces surrounding tissue cells and RES • Enable immune cells to move Components of blood • White blood cells (WBC) or leukocytes • Red blood cells (RBC) • Platelets Figure 15.4 A schematic representation of hematopoiesis Blood stem cell in bone marrow Myeloid stem cell Erythroid stem cell Erythrocyte Platelets Basophil Inflammation Clotting, inflammation Gas transportation Neutrophil Lymphoid stem cell Eosinophil Monocyte Lymphocyte Phagocytosis Innate immunity, second line of defense Leukocytes Adaptive immunity The different stages of hemopoiesis in humans. Fig. 14.8 Stages in hemopoiesis The three types of stem cells differentiate into blood, platelets, granulocytes, and agranulocytes. Fig. 14.9 The development of blood cells and platelets. Before We Can Talk About Innate Immunity Blood as a component of immune response Plasma leaks out of capillaries, taken up into lymphatic vessels and through the lymph nodes to be filtered. Erythrocytes – red blood cells Leukocytes – white blood cells Thrombocytes – platelets 1. Leukocytes a. Granulocytes i. Neutrophils, 55-90% of all WBC’s PMN’s, Polymorphonuclear leukocytes, (polies) - Phagocytic cells, and voracious eaters! - Mostly stay in tissues - Short lived 3-8 days A form of innate response preventing bacteria from spreading and have bactericidal properties NET = Neutrophil Extracellular Trap ii. Eosinophils, 1-3% of all WBC’s -More numerous in bone marrow and spleen than in circulation. -Effective in fighting off eukaryotes like fungi or worms. Contain digestive enzymes and toxic granules. When worms invade, Eosinophils gather around them and release enzymes to kill the worm. iii. Basophils, .5-1% of all WBC’s - These cells are motile and filled with histamine and other chemical mediators. These chemicals result in inflammation and cell communication. - Mast cells are like basophils, but are non motile and found throughout connective tissue. b. Agranulocytes . i. Monocytes (3-8%) can be fixed, or wandering. - Develop into macrophages in the tissues (Differentiate into macrophages (circulation and lymphatics) and dendritic cells (tissue associated) - phagocytic cell (clean up) - Antigen presenting cell - releases chemical mediators - Largest of all WBC’s - Long Lived ii. Lymphocytes (20-35%) - T- lymphocytes train in the thymus (chest area) Cellular immunity. - B – lymphocytes are trained in the bone marrow. Humoral immunity. iii. Dendritic cells - part of monocyte line - primary job is antigen presentation Lymphatic system • Network of vessels that extend to most body areas • Connected to the blood system • Provides an auxiliary route for the return of extracellular fluid to the circulatory system • “Drain off” system for inflammatory response • Contains lymphocytes, phagocytes and antibodies Representation of the lymphatic system. Fig. 14.11 General components of the lymphatic system. Lymphatic system • • • • • • Fluids Vessels Nodes Spleen Thymus Miscellaneous Fluids • Plasma-like fluid (lymph) – Water – Dissolved salts – Proteins (antibodies, albumin) – White blood cells – No red blood cells • Formed from blood components – Diffuse into the lymphatic capillaries Vessels • Parallels the blood system • Returns lymph to the blood system • Movement of lymph depends on muscle contractions • Permeate all parts of the body except the central nervous system, bone, placenta, and thymus. Lymph nodes • Exist in clusters • Located – along the lymphatic channels and blood vessels – in the thoracic and abdominal cavity regions, armpit, groin and neck • Filter for the lymph • Provide environment for immune reactions Spleen • Located in the upper left portion of the abdominal cavity • Filter for blood – traps pathogens and phagocytizes pathogens • Adults can survive without spleen • Asplenic children are severely immunocompromised Thymus • Embryo – two lobes in the pharyngeal region – High activity (releases mature T cells) until puberty • Adult – Gradually shrinks – Lymph node and spleen supply mature T cells Innate Immunity or Non-specific Immunity • • • • Inflammation Phagocytosis Interferon Complement Inflammation • Five major symptoms – Redness – Warmth – Swelling – Pain – Loss of function The typical symptoms that occur after injury. Fig. 14.13 The response to injury Inflammation • Inflammation- a condition brought on by infection, tissue injury, or immune reaction. 1. Inflammation serves to: a. mobilize & attract immune cells to the site b. mobilize repair, and clean up of site c. destroy microbes & block further infection Function • Mobilize and attract immune components to the site of injury • Aid in the repair of tissue damage • Localized and remove harmful substances • Destroy microbes and block their invasion Causes • Trauma • Tissue injury due to physical or chemical agents • Specific immune reactions The major events in inflammation are injury, vascular reactions, edema, and resolution. Fig. 14.14 The major events in inflammation Stages • Vascular changes • Edema • Fever Vascular changes • Blood cells, tissue cells, and platelets release chemical mediators and cytokines • Chemical mediators – Vasoactive • Affect endothelial cells, smooth muscles of blood vessels – Chemotactic (chemokines) • Affect WBC Altering capillaries a. Increased vessel dilation i. Blood supply to tissue increases ii. Able to carry more leukocytes and serum proteins iii. Also causes erythema, (redness) and warmth. b. Increased vessel permeability i. Allows the leukocytes to move into tissue, though also allows fluids to leak as well. ii. Margination iii. Diapedesis iiii. Pain Chemical mediators • Cause fever, stimulate lymphocytes, prevent virus spread, cause allergic reactions – Vasoactive mediators • Affect endothelial cells, smooth muscles of blood vessels – Chemotactic (chemokines) mediators • Affect WBC Representation of the effects of chemical mediators during inflammation. Fig. 14.15 Chemical mediators of the inflammatory response and their effects. Edema • Leakage of vascular fluid (exudate) into tissue • Exudate - plasma proteins, blood cells (wbc), debris, and pus • Migration of wbc is called diapedesis or transmigration – Chemotaxis The transmigration of WBCs is followed by chemotaxis. Fig. 14.16 Diapedesis and chemotaxis of leukocytes. Inflammatory repair and acute inflammation a. Inflammation can be painful, debilitating but effective in fighting infection and cleaning up. i. The area fills with dead leukocytes, bacteria and tissue cells, this mix is called pus. ii. Macrophages will begin clean up by consuming the dead and dying cells. b. But, the same inflammation can damage normal healthy tissue surrounding the site if it goes on too long. Autoimmune disorders. Fever 1. Systemic body wide physiological response to infection cytokines tell the hypothalamus to increase temperature. 2. Three parts to fever: Chill, fever, crisis. a. Chill - Physical reactions, goose bumps or shivering occur, heat is increasing. b. Fever – prolonged elevated temperature. c. Crisis – sweating and cooling of body temperature. 3. The increased temp. is actually the optimal temp. for phagocytic cell activity. Inhibits temp sensitive microbes such as cold virus, or mycobacterium. Fever • Caused by pyrogens – reset the hypothalamic thermostat (increase temperature) – Vasoconstriction • Pyrogens – Microbes and their products (ex. LPS) – Leukocyte products (ex. lnterleukins) • Inhibits microbe and viral multiplication, reduces nutrient availability, increases immune reactions Figure 15.15 One theoretical explanation for the production of fever in response to infection Hypothalamus Hypothalamus secretes prostaglandin, which resets hypothalamic thermostat. Chemicals secreted by phagocytes travel in blood to hypothalamus. Nerve impulses cause shivering, higher metabolic rate, inhibition of sweating, and vasoconstriction. Wound These processes increase body termperature to the point set by the hypothalamic thermostat. Phagocytosis • Neutrophils and eosinophils • Macrophages • Mechanism Phagocytosis • Phagocytes recognize, engulf and destroy invading pathogens. • Macrophages and neutrophils • Principle means of eliminating pathogens! • 4 steps to phagocytosis: 1. Recognition 2. Engulfment 3. Digestion 4. Expulsion Neutrophils and eosinophils • Early responders to inflammation • Neutrophils are primary components of pus • Eosinophils are primary responders to parasitic infections Macrophages • Monocytes transform into macrophages • Scavengers – Histiocytes – reside in one location (ex. Alveolar, Kupffer, Langerhans) – Drift throughout the RES • Undergo phagocytosis, • Interact with B and T cells 1. Recognition a. Phagocytes have proteins called cell surface receptors. These bind to the antigenic determinants of pathogens. i. Recognizes cells different from “self” ii. LPS of gram negatives iii. Peptidoglycan b. Complement proteins help to form a bridge between the macrophage and the pathogen aiding phagocytosis. (opsonization) 2. Engulfment & 3. Digestion a. Once attached, the macrophage extends pseudopods around the pathogen and engulfs it, producing a phagosome (a membrane bound vacuole, or pocket) b. The phagosome merges with a lysosome forming a phagolysosome, and the chemicals within it digest the pathogen. Usually in 30 minutes or less! (or the next one is free! Ha ha!) Destruction • Within the phagolysosome – Oxygen-dependent system • Oxidative burst (oxidizing agents) – Enzymes – Nitric oxide • Undigestible debris are released 4. Expulsion a. After digestion the phagolysosome fuses with the cell membrane and expels undigested materials. A summary of the mechanism of phagocytosis. Fig. 14.19 The phases in phagocytosis Interferon • Produced due to viral infections, microbe infections, RNA, immune products, and antigens Virus specific defenses Interferons – small proteins that impair viral replication, and are passed from virally infected cells to neighboring healthy cells. a. Virus nonspecific, very potent. Complement • Consist of 26 blood proteins • Produced by liver hepatocytes, lymphocytes, and monocytes • Pathways • Cascade reaction • Stages Complement (complement cascade) Complement – a defense system consisting of serum proteins found in blood, lymph, and extra cellular fluids. 1. Consequences of the complement cascade a. Cytolysis - bursting the invaders cell wall. b. Initiate inflammation - cascade protein lyses a mast cell releasing histamine, and enacting inflammation. c. Opsonization - “prepare for dinner” cascade proteins attach to capsule enabling the macrophage to engulf it more easily. 2. Methods of triggering complement a. Classical pathway- complement is activated by the presence of an antibody bound to a microorganism. b. Lectin pathway- when a host protein binds to a sugar present in the walls of fungi and other microbes. c. Alternative pathway – complement proteins bind to normal cell wall and/or surface components of microbes. The three complement pathways, their activators, and the complement proteins involved. Table 14.1 Complement pathways Stages • • • • Initiation Amplification and cascade Polymerization Membrane attack Membrane attack complex