Microbiology: A Systems Approach, 2nd ed. Chapter 14: Host Defenses IOverview and Nonspecific Defenses 14.1 Defense Mechanisms of the Host in Perspective Figure 14.1 Barriers at the Portal of Entry: A First Line of Defense Figure 14.2 Figure 14.3 Nonspecific Chemical Defenses • Sebaceous secretions and specialized glandsantimicrobial • Lysozyme in tears • Lactic acid and electrolyte concentrations of sweat • Skin’s acidic pH and fatty acid content • HCl in the stomach • Digestive juices and bile in the intestine • Semen- antimicrobial chemical • Acidic pH in the vagina Genetic Differences in Susceptibility • Some hosts are genetically immune to the diseases of other hosts • Particularly true of viruses 14.2 The Second and Third Lines of Defense: An Overview • Immunology: the study of all features of the body’s second and third lines of defense • Healthy functioning immune system is responsible for: – Surveillance of the body – Recognition of foreign material – Destruction of entities deemed to be foreign Figure 14.4 Self and Nonself • White blood cells must distinguish self from nonself cells • Evaluates cells by examining markers on their surfaces 14.3 Systems Involved in Immune Defenses • Body compartments – Intracellular – Extracellular – Lymphatic – Cerebrospinal – Circulatory • Physically separated but have numerous connections Body Compartments that Participate in Immune Function • • • • Reticuloendothelial system (RES) Spaces containing extracellular fluid (ECF) Bloodstream Lymphatic system The Communicating Body Compartments Figure 14.5 Immune Functions of the Reticuloendothelial System • Provides a passageway within and between tissues and organs • Coexists with the mononuclear phagocyte system Figure 14.6 Origin, Composition, and Functions of the Blood • Circulatory system – Circulatory system proper – Lymphatic system Figure 14.7 Fundamental Characteristics of Plasma • Hundreds of different chemicals • Main component is water (92%) • Proteins such as albumin and globulins, immunochemicals, fibrinogen and other clotting factors, hormones, nutrients, dissolved gases, and waste products A Survey of Blood Cells • Hematopoesis: production of blood cells • Relatively short life • Primary precursor of new blood cells: pluripotential stem cells in the marrow – Red blood cells (erythrocytes) – White blood cells (leukocytes) – Platelets (thrombocytes) • Differentiation Figure 14.8 (a) Figure 14.9 (b) Leukocytes • Granulocytes • Agranulocytes Granulocytes • Neutrophils – Phagocytosis • Eosinophils – Attack and destroy large eukaryotic pathogens – Also involved in inflammation and allergic reactions • Basophils – Parallel eosinophils in many actions Agranulocytes • Monocytes • Lymphocytes Monocytes • Discharged by bone marrow into bloodstream, live as phagocytes for a few days, then differentiate into macrophages • Responsible for – Many specific and nonspecific phagocytic and killing functions – Processing foreign molecules and presenting them to lymphocytes – Secreting biologically active compounds that assist, mediate, attract, and inhibit immune cells and reactions • Dendritic cells Lymphocytes • Key cells in the third line of defense and the specific immune response • When stimulated by antigens, transform into activated cells that neutralize and destroy that foreign substance • B cells – Humoral immunity: protective molecules carried in the fluids of the body – Produce specialized plasma cells which produce antibodies • T cells – Cell-mediated immunity: T cells modulate immune functions and kill foreign cells Erythrocyte and Platelet Lines • Erythrocytes – Develop from stem cells in the bone marrow – Lose their nucleus just prior to entering circulation – Transport oxygen and carbon dioxide to and from the tissues • Platelets – Formed elements in circulating blood – Not whole cells – Function primarily in hemostasis and in releasing chemicals for blood clotting and inflammation Components and Functions of the Lymphatic System • Lymphatic system: compartmentalized network of vessels, cells, and specialized accessory organs • Transports lymph through a system of vessels and lymph nodes • Major functions – Provide an auxiliary route for the return of extracellular fluid to the circulatory system proper – Act as a drain-off system for the inflammatory response – Render surveillance, recognition, and protection against foreign materials Figure 14.10 Lymphatic Fluid • Lymph • Plasmalike liquid formed when certain blood components move out of blood vessels into the extracellular spaces and diffuse or migrate into the lymphatic capillaries • Composition parallels that of plasma, but without red blood cells Lymphatic Vessels • Along the lines of blood vessels • Similar to thin-walled veins • High numbers in hands, feet, and around the areola of the breast • Flow of lymph is in one direction only- from extremities toward the heart • Lymph is moved through the contraction of skeletal muscles through which the lymphatic ducts wend their way Lymphoid Organs and Tissues • • • • • • Lymph nodes Thymus Spleen Gut-associated lymphoid tissue (GALT) Tonsils Loose connective tissue framework that houses aggregations of lymphocytes Lymph Nodes • Small, encapsulated, bean-shaped organs • Usually found in clusters along lymphatic channels and large blood vessels of the thoracic and abdominal cavities • Major aggregations: axillary nodes, inguinal nodes, cervical nodes Spleen • Similar to a lymph node except it filters blood instead of lymph • Filters pathogens from the blood The Thymus: Site of T-Cell Maturation • • • • Thymus originates in the embryo High rates of activity and growth until puberty Shrinks gradually through adulthood Thymic hormones help thymocytes develop specificity to be released as mature T cells Figure 14.11 Miscellaneous Lymphoid Tissue • Bundles of lymphocytes lie at many sites on or just beneath the mucosa of the gastrointestinal and respiratory tracts • Tonsils • Breasts of pregnant and lactating women • GALT in the intestinal tract – Appendix – Lacteals – Peyer’s patches • Mucosal-associated lymphoid tissue (MALT) • Skin-associated lymphoid tissue (SALT) • Bronchial-associated lymphoid tissue (BALT) 14.2 The Second Line of Defense • • • • Inflammation Phagocytosis Interferon Complement The Inflammatory Response: A Complex Concert of Reactions to Injury • Reaction to any traumatic event in the tissues • Classic signs and symptoms – Rubor (redness) – Calor (warmth) – Tumor (swelling) – Dolor (pain) • Fifth symptom has been added: loss of function Figure 14.12 Chief Functions of Inflammation • Chief functions of inflammation – Mobilize and attract immune components to the site of the injury – Set in motion mechanisms to repair tissue damage and localize and clear away harmful substances – Destroy microbes and block their further invasion The Stages of Inflammation Figure 14.13 Vascular Changes: Early Inflammatory Events • Controlled by nervous stimulation, chemical mediators, and cytokines released by blood cells, tissue cells, and platelets in the injured area • Vasoactive mediators affect the endothelial cells and smooth muscle cells of blood vessels • Chemotactic factors (chemokines) affect white blood cells • Cause fever, stimulate lymphocytes, prevent virus spread, and cause allergic symptoms • Arterioles constricted at first but quickly vasodilation takes place Edema: Leakage of Vascular Fluid into Tissues • Exudates: the fluid that escapes through gaps in the walls of postcapillary venules • Accumulation of exudates causes edema • Contains plasma proteins, blood cells, and cellular debris • May be clear (serous) or may contain red blood cells or pus • Diapedesis: how WBCs leave the blood vessels and into tissue spaces • Chemotaxis: the tendency of WBCs to migrate in response to a specific chemical stimulus Benefits of Edema and Chemotaxis • Dilutes toxic substances • Fibrin clot can trap microbes and prevent further spreading • Phagocytosis occurs immediately Figure 14.14 Late Reactions of Inflammation • Long-lived inflammation attracts a collection of monocytes, lymphocytes, and macrophages to the reaction site • Macrophages clear pus, cellular debris, dead neutrophils, and damaged tissue • B lymphocytes produce antibodies • T lymphocytes kill intruders directly • Late in the process the tissue is repaired or replaced by connective tissue (scar) Fever: An Adjunct to Inflammation • An abnormally elevated body temperature • FUO: fevers of unknown origin • Initiation of fever – Pyrogen sets the hypothalamic “thermostat” to a higher setting • Muscles increase heat production • Peripheral arterioles decrease heat loss through vasoconstriction – Pyrogens can be exogenous or endogenous Benefits of Fever • Inhibits multiplication of temperaturesensitive microorganisms • Impedes the nutrition of bacteria by reducing the availability of iron • Increases metabolism and stimulates immune reactions and naturally protective physiological processes Phagocytosis: Cornerstone of Inflammation and Specific Immunity • General activities of phagocytes – Survey the tissue compartments and discover microbes, particulate matter, and injured or dead cells – Ingest and eliminate these materials – Extract immunogenic information (antigens) from foreign matter • Three main types – Neutrophils – Monocytes – Macrophages Figure 14.15 Figure 14.16 Mechanisms of Phagocytic Recognition, Engulfment, and Killing Figure 14.17 Interferon: Antiviral Cytokines and Immune Stimulants • Interferon (IFN): involved against viruses, other microbes, in immune regulation and intercommunication • Three major types – Interferon alpha – Interferon beta – Interferon gamma • All three classes produced in response to viruses, RNA, immune products, and various antigens • Bind to cell surfaces and induce changes in genetic expression • Can inhibit the expression of cancer genes and have tumor suppressor effects Figure 14.18 Complement: A Versatile Backup System • At least 26 blood proteins that work in concert to destroy bacteria and certain viruses • Cascade reaction • Three different pathways that all yield similar end results – Classical pathway – Lectin pathway – Alternative pathway Complement Cascade • • • • Initiation Amplification and cascade Polymerization Membrane attack Classical Pathway Figure 14.19