Chapter 14 - Fall 2024 PDF

Because learning changes everything.® Chapter 14 An Introduction to Host Defenses and Innate Immunities Talaro’s Foundations in Microbiology Twelfth Edition Barry Chess © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of Mc...

Because learning changes everything.® Chapter 14 An Introduction to Host Defenses and Innate Immunities Talaro’s Foundations in Microbiology Twelfth Edition Barry Chess © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC.  Overview of Host Defense Mechanisms Innate, natural defenses: present at birth, provide nonspecific resistance to infection Adaptive immunities: specific, must be acquired © McGraw Hill, LLC 2  Defense Mechanisms of the Host To protect the body against pathogens, the immune system relies on a multilevel network of physical barriers, immunologically active cells, and a variety of chemicals First line of defense – any barrier that blocks invasion at the portal of entry – nonspecific Second line of defense – protective cells and fluids; inflammation and phagocytosis – nonspecific Third line of defense – acquired with exposure to foreign substance; produces protective antibodies and creates memory cells – specific The lines of defense do not work separately, most overlap and are redundant in some of their effects © McGraw Hill, LLC 3  1st Line of Defense: Barriers at the Portal of Entry A number of defenses are a normal part of the body’s anatomy and physiology These are inborn (innate), nonspecific defenses They can be divided into three categories: 1. Physical or anatomical barriers at the body surface 2. Chemical defenses 3. Genetic resistance to infection They block the entry of not only microbes but any foreign agent (living or not) © McGraw Hill, LLC 4  Physical or Anatomical Barriers Built-in defenses in skin Outermost layer of skin with epithelial cells cemented together, and impregnated with keratin Flushing effect of sweat Mucous membranes Coating of digestive, genitourinary, and respiratory tracts Blinking and tear production Flow of saliva Flushing effect of urination, defecation, vomiting © McGraw Hill, LLC 5  Physical or Anatomical Barriers Mucous membranes Mucous coat impedes attachment and entry of bacteria Ciliary defense of respiratory tree; nasal hair traps larger particles Epithelial cells in the trachea are covered in tufts of cilia that sweep mucus, filled with small particles and microbes, up and away from the lungs. © McGraw Hill, LLC 6  Nonspecific Chemical Defenses From skin and mucous membranes (antimicrobial effect) Sebaceous secretions Antimicrobial secretions from specialized glands (meibomian glands) Other defenses in tears, saliva and skin: Lysozyme, an enzyme that hydrolyzes the cell wall of bacteria Defensins, peptides that lyse bacteria and fungi High lactic acid and electrolyte concentration in sweat Skin’s acidic pH © McGraw Hill, LLC 7  Nonspecific Chemical Defenses Hydrochloric acid in stomach Digestive juices and bile of intestines Semen contains an antimicrobial chemical Vagina has acidic pH (maintained by microbiota) © McGraw Hill, LLC 8  Genetic Defenses Some hosts are genetically immune to the diseases of other hosts “Humans can’t acquire distemper from cats, and cats can’t get mumps from humans” Viruses have great specificity for their host receptors Some genetic differences in susceptibility exist for other pathogens, including differences within members of the same species Humans carrying a gene or genes for sickle-cell anemia are resistant to malaria © McGraw Hill, LLC 9  Structure and Function of the Organs of Defense and Immunity Immunology: study of the body’s 2nd and 3rd lines of defense Primary functions of a healthy immune system: 1. Surveillance of the body 2. Recognition and differentiation of normal versus foreign material 3. Attack against and destruction of entities deemed to be foreign © McGraw Hill, LLC 10  Structure and Function of the Organs of Defense and Immunity White blood cells (leukocytes) – innate capacity to recognize and differentiate any foreign material Nonself – foreign material Self – normal cells of the body © McGraw Hill, LLC 11  How do White Blood Cells Work? Pathogen-associated patterns (PAMPs) – molecules shared by microorganisms Pathogen recognition receptors (PRRs) – receptors on WBCs for PAMPs © McGraw Hill, LLC 12  Components and Connections of the Immune System The immune system is a large, complex, and diffuse network of cells and fluids that penetrate into every organ and tissue Body compartments that participate in immune function: 1. Reticuloendothelial system (RES) 2. Extracellular fluid (ECF) 3. Bloodstream 4. Lymphatic system For effective immune responsiveness, the activities in one fluid compartment must be conveyed to other compartments © McGraw Hill, LLC 13  Connections Between Body Compartments Connection between body compartments, involved in the immune system. The meeting of the major compartments at the microscopic level allows for continuous exchange of cells, fluids, and molecules (arrows) MPS = mononuclear phagocyte system © McGraw Hill, LLC 14  Reticuloendothelial System (RES) Network of connective tissue fibers that interconnects other cells and meshes with the connective tissue network surrounding organs Inhabited by phagocytic cells – mononuclear phagocyte system – macrophages ready to attack and ingest microbes that passed the first line of defense © McGraw Hill, LLC 15  Origin, Composition, and Functions of Blood Whole blood: plasma and formed elements (blood cells) Serum: liquid portion of blood after a clot has formed (minus clotting factors) Plasma – 92% water, metabolic proteins, globulins, clotting factors, hormones, and other chemicals and gases to support normal physiological functions © McGraw Hill, LLC 16  A Survey of Blood Cells Hemopoiesis (or hematopoiesis)– production of blood cells Stem cells – undifferentiated cells, precursor of new blood cells Primary cell lines: Platelets (thrombocytes) Red blood cells (RBCs) Leukocytes or white blood cells (WBCs), responsible for immune function Granulocytes: lobed nucleus Agranulocytes: unlobed, rounded nucleus © McGraw Hill, LLC 17  Blood Cell and Platelet Development © McGraw Hill, LLC 18  Granulocytes Neutrophils – 55 to 90% - lobed nuclei with lavender granules; phagocytes Eosinophils – 1 to 3% - orange granules and bilobed nucleus; destroy eukaryotic pathogens Neutrophil Basophils – 0.5% - bilobed nuclei, dark blue granules; release potent chemical mediators Mast cells: nonmotile elements bound to connective tissue Eosinophil © McGraw Hill, LLC 19  Agranulocytes Lymphocytes – 20 to 35%, specific immune response B (humoral immunity): activated B cells produce antibodies T cells (cell-mediated immunity): activated T cells modulate immune functions and kill foreign cells Monocytes – 3 to 7% - largest of WBCs, kidney- shaped nucleus; phagocytic Macrophages: final differentiation of monocytes after leaving the circulation system Dendritic cells: trap pathogens and participate in immune reactions © McGraw Hill, LLC 20  Leukocytes © McGraw Hill, LLC 21  Medical Moment: Syphilis C.A. = Treponema – Some medical pallidum historians claim the disease originated in – Spirochete; motile by the Western axial filament; hemisphere and was fastidious! brought back to Europe by Columbus's crew – Others say it evolved from other mo’s…. Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Epidemiology: Humans are the only reservoirs Transmission by sexual contact or with saliva In 2020, 133,945 cases of all stages of syphilis were reported, 44,784 estimated new diagnoses of HIV infection (2014) and 395,216 cases of gonorrhea (2015) Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Epidemiology In the 1990s, syphilis primarily occurred among heterosexual men and women of racial and ethnic minority groups However in 2000, cases have increased among men who have sex with men (MSM). – In 2002, rates of P&S syphilis were highest among men 30–39 years-old, – by 2011, were highest among men 20–29 years- old This epidemiologic shift reflects increasing cases reported among young MSM in recent years – MSM accounted for 72% of all P&S syphilis cases in 2011. http://www.promedmail.org/direct.php?id=3304654 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Sexually Transmitted Infections 25 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  26 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Epidemiology Figure 35. Syphilis — Rates of Reported Cases by Stage of Infection, United States, 1941–2017 NOTE: Data collection for syphilis began in 1941; however, syphilis became nationally notifiable in 1944. Refer to the National Notifiable Disease Surveillance System (NNDSS) website for more information: https://wwwn.cdc.gov/nndss/conditions/syphilis/ Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Figure 36. Primary and Secondary Syphilis — Rates of Reported Cases by Region, United States, 2008–2017 28 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Figure 37. Primary and Secondary Syphilis — Rates of Reported Cases by State, United States and Outlying Areas, 2017 NOTE: The total rate of reported cases of primary and secondary syphilis for the United States and outlying areas (including Guam, Puerto Rico, and the Virgin Islands) was 9.5 per 100,000 population. ACRONYMS: GU = Guam; PR = Puerto Rico; VI = Virgin Islands. 29 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Symptoms: Three stages Primary Stage Many do not have any symptoms for years. The primary stage a sore (called a chancre), may be multiple sores. Incubation time = 10 to 90 days (average 21 days). Chancre = firm, round, small, and painless. Chancre appears at the spot where syphilis entered the body. Chancre lasts 3 to 6 weeks, and it heals without treatment. Syphilis can infect the CNS at any time during infection. Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Secondary Stage Syphilis Skin rash and mucous membrane lesions characterize Not itchy Can appear as the chancre is healing or several weeks after Rough, red, or reddish brown (copper) spots (palms and soles) Can be faint = not noticed. In addition to rashes may have: – fever, swollen lymph glands, sore throat, patchy hair loss, headaches, weight loss, muscle aches, and fatigue. The signs and symptoms of secondary syphilis will resolve with or without treatment. Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Late Stage Syphilis The latent (hidden) stage of syphilis begins when secondary symptoms disappear. In the late stages of syphilis, – damage the internal organs, including the brain, nerves, eyes, heart, blood vessels, liver, bones, and joints. – difficulty coordinating muscle movements, paralysis, numbness, gradual blindness, and dementia. – may be serious enough to cause death. Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Three stages of Syphilis: Chancre Rash Gumma Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Congenital Syphilis Can cause: If baby is born alive with Syphilis: Miscarriage (losing the Deformed bones, baby during Severe anemia (low blood pregnancy), count), Stillbirth (a baby born Enlarged liver and spleen, dead), Jaundice (yellowing of the Prematurity (a baby skin or eyes), born early), Brain and nerve problems, like blindness or deafness, Low birth weight, or Meningitis, and Death shortly after Skin rashes. birth. 34 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Prevention Long-term mutually monogamous relationship Avoid activities that lead to risky sexual behavior. Correct and consistent use of latex condoms Transmission cannot be prevented by washing the genitals, urinating, and or douching after sex Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Syphilis: Treatment Treatments: – single injection of long-acting Benzathine penicillin G (for primary and secondary phases) No immunity with recovery U.S. Public Health Service Syphilis Study at Tuskegee http://www.cdc.gov/tuskegee/index.html Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Erythrocytes and Platelet Lines Erythrocytes: develop from bone marrow stem cells, lose nucleus, simple biconcave sacs of hemoglobin Platelets: formed elements in circulating blood that are not whole cells © McGraw Hill, LLC 37  Lymphatic System Provides an auxiliary route for return of extracellular fluid to the circulatory system Acts as a drain-off system for the inflammatory response Renders surveillance, recognition, and protection against foreign material © McGraw Hill, LLC 38  Lymphatic Fluid Lymph is a plasma-like liquid carried by lymphatic circulation Formed when blood components move out of blood vessels into extracellular spaces Made up of water, dissolved salts, 2 to 5% proteins Transports white blood cells, fats, cellular debris, and infectious agents © McGraw Hill, LLC 39  Lymphatic Vessels Lymphatic capillaries permeate all parts of the body except the CNS, bone, placenta, and thymus Thin walls easily permeated by extracellular fluid which is then moved through contraction of skeletal muscles Functions to return lymph to circulation; flow is unidirectional – toward the heart – eventually returning to blood stream © McGraw Hill, LLC 40  Classification of Lymphoid Organs and Tissues Primary organs Sites of lymphocytic origin and maturation Thymus gland Bone marrow Secondary organs and tissues Circulatory-based locations, encounter microbes Lymph nodes Spleen MALT – mucosal-associated lymphoid tissue GALT – gut-associated lymphoid tissue (Peyer’s patches) © McGraw Hill, LLC 41  Lymphoid Organs Thymus High growth and activity until puberty, then begins to shrink Site of T-cell maturation Lymph nodes Small, encapsulated, bean- shaped organs along lymphatic channels and large blood vessels of the thoracic and abdominal cavities Filters lymph; provides niches for immune reactions © McGraw Hill, LLC 42  Lymphoid Organs Spleen Nestled below the diaphragm and left of the stomach Structurally similar to lymph node; filters circulating blood to remove worn out RBCs and pathogens © McGraw Hill, LLC 43  Second-Line Defenses: Inflammation Mechanisms that play important roles in host defenses: Inflammation Phagocytosis Interferon Complement Nonspecific in their effects but Inflammatory Response they support and interact with specific immune responses © McGraw Hill, LLC 44  Inflammatory Response Reaction to any traumatic event in the tissues that attempts to restore homeostasis Helps to clear away invading microbes and cellular debris left by immune reactions Redness (Rubor) – increased circulation and vasodilation in response to chemical mediators Warmth (Calor) – heat given off by the increased blood flow Swelling (Tumor) – increased fluid in the tissue as blood vessels dilate – edema; WBC’s, microbes, debris, and fluid collect to form pus; prevents spread of infection Pain (Dolor) – stimulation of nerve endings © McGraw Hill, LLC 45  Major Inflammatory Events a) Injury/Immediate Reactions: Blood vessels narrow (vasoconstriction); blood clots; and mast cells release chemokines and cytokines into injured area. © McGraw Hill, LLC 46  Major Inflammatory Events b) Vascular Reactions: Nearby blood vessels dilate; increased blood flow; increased vascular permeability; increased leakage of fluid forms exudate. © McGraw Hill, LLC 47  Major Inflammatory Events c) Edema and Pus Formation: Collection of fluid; edema/swelling; infiltration by neutrophils and formation of pus. © McGraw Hill, LLC 48  Major Inflammatory Events d) Resolution/Scar Formation: Macrophages lymphocytes, and fibroblasts migrate in; initiate immune response and repair of injury; scar and loss of normal tissue. © McGraw Hill, LLC 49  Chemical Mediators of Inflammatory Response Formation of a blood clot. After an injury, fibrinogen is converted to insoluble fibrin threats that ensnare red blood cells. White blood cells and platelets are also trapped, helping to stop bleeding (SEM 3250x) © McGraw Hill, LLC 50  Unique Characteristics of Leukocytes Diapedesis – migration of cells out of blood vessels into the tissues Chemotaxis – migration in response to specific chemicals at the site of injury or infection © McGraw Hill, LLC 51  Fever: An Adjunct to Inflammation Initiated by circulating pyrogens which reset the hypothalamus to increase body temperature; signals muscles to increase heat production and vasoconstriction Exogenous pyrogens – products of infectious agents; endotoxin Endogenous pyrogens – liberated by monocytes, neutrophils, and macrophages during phagocytosis; interleukin-1 (IL-1) and tumor necrosis factor (TNF) © McGraw Hill, LLC 52  Fever: An Adjunct to Inflammation Benefits of fever: Inhibits multiplication of temperature-sensitive microorganisms Impedes nutrition of bacteria by reducing the available iron Increases metabolism and stimulates immune reactions and protective physiological processes © McGraw Hill, LLC 53  Second-Line of Defenses: Phagocytosis General activities of phagocytes: 1. To survey tissue compartments and discover microbes, particulate matter, and dead or injured cells 2. To ingest and eliminate these materials 3. To extract immunogenic information from foreign matter © McGraw Hill, LLC 54  Second-Line of Defenses: Phagocytosis Major categories of phagocytes: Neutrophils – general-purpose; react early to bacteria and other foreign materials, and to damaged tissue Eosinophils – attracted to sites of parasitic infections and antigen-antibody reactions Macrophages – derived from monocytes; scavenge and process foreign substances to prepare them for reactions with B and T lymphocytes © McGraw Hill, LLC 55  Production of neutrophil extracellular traps 1) Granules within the cytoplasm of the neutrophil release the enzyme neutrophil elastase (NE) 2) NE travels to the nucleus of the cell and cleaves proteins needed to package the cell’s DNA into chromosomes. 3)As the chromosomes decondense, DNA fills the cell. 4) the neutrophil lyses, propelling the net outward, where it traps pathogenic cells. © McGraw Hill, LLC 56  Development of Monocytes and Macrophages After leaving the bloodstream and entering the tissue, monocytes are transformed by inflammatory mediators into macrophages or dendritic cells Macrophage and dendritic cells can remain nomadic or take up residence in a specific organ © McGraw Hill, LLC 57  Erythrocytes: A role in the immune system RBCs – thought to be only mechanical carriers of oxygen and carbon dioxide May be especially adept at collecting pathogenic cell-free DNA from circulatory system Cells carrying these DNA are targeted by immune system; helps in triggering immune response © McGraw Hill, LLC 58  Phagocytic Recognition Protein receptors within cell membrane of macrophages, called Toll-like receptors (TLRs) Detect foreign molecules and signal the macrophage to produce chemicals to stimulate an immune response © McGraw Hill, LLC 59  Mechanisms of Phagocytosis Chemotaxis, binding and ingestion Phagocytes migrate to inflamed site following a gradient of stimulant products Using TLRs they bind pathogen-associated molecular pattern (PAMPs) receptors Phagolysosome formation Phagocyte extends pseudopods that enclose pathogen in a vacuole called a phagosome In a short time, lysosomes with antimicrobial substances fuse with the phagosome to form a phagolysosome and digest the pathogen © McGraw Hill, LLC 60  Mechanisms of Phagocytosis Destruction and elimination Oxygen-dependent system (respiratory burst) Liberation of lactic acid, lysozyme, and nitric oxide Undigestible debris are released from the macrophage by exocytosis © McGraw Hill, LLC 61  Sequential Events in Phagocytosis Source: National Institute of Allergy and Infectious Diseases (NIAID) © McGraw Hill, LLC 62  Interferon Small protein produced by certain WBCs and tissue cells Three major types of IFNs: Interferon alpha – product of lymphocytes and macrophages Interferon beta – product of fibroblasts and epithelial cells Interferon gamma – product of T cells All produced in response to viruses, RNA, immune products, and antigens © McGraw Hill, LLC 63  Interferon All three types bind to cell surfaces and induce expression of antiviral proteins and inhibit expression of cancer genes IFNs alpha and beta stimulate phagocytes IFN gamma is an immune regulator of macrophages and T and B cells © McGraw Hill, LLC 64  Complement Consists of at least 30 blood proteins that work in concert to destroy bacteria and viruses Complement proteins are activated by cleavage (cascade reaction) Three primary defensive features: Membrane attack complex (MAC) – kills pathogen directly Opsonization – coating pathogen to promote phagocytosis Recruitment of inflammatory cells and cytokine release © McGraw Hill, LLC 65  4 Stages in the Complement Cascade © McGraw Hill, LLC 66  4 Stages in the Complement Cascade b) Cascade and Amplification. C5 factor is acted on by C3b, which converts it to C5b. C5b becomes bound to the membrane and serves as the starting molecule for the chain of events that assemble the complex in (c) and (d). c) Polymerization. C5b is a reactive site for the final assembly of an attack complex. In series, C6, C7, and C8 aggregate with C5b and become integrated into the membrane. They form a substrate upon which the final component, C9, can bind. Up to 15 of these C9 units ring the central core of the final membrane attack complex (MAC). d) Membrane Attack. Insertion of MACs produces hundreds of tiny holes in the cell membrane. This can cause lysis and death of eukaryotic cells and many gram- negative bacteria. © McGraw Hill, LLC 67  4 Stages in the Complement Cascade Two products of the cascade reaction — C3a and C5a — have additional inflammatory functions. Both molecules stimulate mast cell degranulation, enhance chemotaxis of white blood cells, and act as inflammatory mediators. © McGraw Hill, LLC 68  Overview of the Major Host Defenses HOST DEFENSES Innate, nonspecific First line of defense Physical barriers Chemical barriers Genetic barriers The first line of defense is a surface protection composed of anatomical and physiological barriers that keep microbes from penetrating sterile body compartments. © McGraw Hill, LLC 69  Overview of the Major Host Defenses Second line of defense Inflammatory response Interferons Phagocytosis Complement The second line of defense is a cellular and chemical system that comes immediately into play if infectious agents make it past the surface defenses. Examples include phagocytes that destroy foreign matter, and inflammation which holds infections in check. © McGraw Hill, LLC 70  Overview of the Major Host Defenses Acquired, specific Third line of defense B and T lymphocytes, antibodies, cytotoxicity The third line of defense includes specific host defenses that must be developed uniquely for each microbe through the action of specialized white blood cells. This form of immunity is marked by its activity toward specific pathogens and development of memory. © McGraw Hill, LLC 71  Because learning changes everything. ® www.mheducation.com © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC.  Chapter 14 Review How is the innate immune system different from the adaptive immune system? Describe the three lines of defense. What are the functions of a healthy immune system? Outline the four major subdivisions of the immune system. (Components and Connections) Differentiate between different granulocytes. 73 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Chapter 14 Review What is the lymphatic system and circulation in the lymphatic vessels? Identify the primary and secondary lymphoid organs/tissues. Discuss the inflammatory response. Outline the different phagocytes and the role they play through phagocytosis. Summarize compliment. 74 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.