BI 127 Microbiology - Innate Nonspecific Host Defenses - PDF

BI 127 Microbiology Chapter 17 Kate E. Kryger Innate Nonspecific Host Defenses Part I: Background Anatom...

BI 127 Microbiology Chapter 17 Kate E. Kryger Innate Nonspecific Host Defenses Part I: Background Anatomy & Physiology I. Overview of the Immune Response The immune response is a function of various components of the major body systems/compartments that work hand-in-hand: A. Blood – Leukocytes and various constituents of plasma B. Lymphatic system – Lymphoid tissues/organs and cells C. Extracellular fluid compartments II. Leukocytes Leukocytes demonstrate diapedesis (ability to migrate between cells) and chemotaxis; and function outside of the circulation: They use the vascular system as a mode of transportation. There are five types of leukocytes: 1. Neutrophils are the first WBCs to arrive at an infection site: They phagocytize foreign particles. 2. Eosinophils defend against parasitic worm infestations by secreting cytotoxic enzymes 3. Basophils migrate to damaged tissues, where they release: Histamine promotes inflammation Heparin inhibits blood clotting and thus increases blood flow to injured tissues 4. Monocytes leave the bloodstream to become macrophages, which phagocytize foreign particles. 5. Lymphocytes are involved in antibody-mediated immunity and cell-mediated immunity B-cells produce antibodies T-cells directly attack microorganisms, tumor cells and transplanted cells NOTE: Lymphocytes are responsible for the body’s specific defenses: They selectively mount counterattacks against particular invading pathogens or specific foreign proteins. III. Lymphatic System Lymphatic system consists of two semi-independent parts, which filter out microbes from fluids surrounding cells. a. A network of lymphatic vessels transports interstitial fluid (lymph) back to the blood. b. Various lymphoid tissues and organs scattered throughout the body house phagocytic cells and lymphocytes, which play essential roles in the body’s defense mechanisms and resistance to disease. A. Lymphoid organs (FYI): House phagocytic cells & lymphocytes 1. Lymph Nodes: Lymphoid organs positioned along the lymph vessels 2. Thymus gland & spleen: immune cells (especially lymphocytes) develop or reside here 3. Tonsils 4. Peyer’s patches (in the intestines) 5. Appendix B. Functions of the Lymphatic System 1. Collects lymph and returns it to the circulation 2. Transports digested lipids to the bloodstream 3. **Contributes to both non-specific & specific host defense 1 of 6 BI 127 Microbiology Chapter 17 Kate E. Kryger Innate Nonspecific Host Defenses Part II: Overview of Host Defenses I. Reasons Infection or Disease Does Not Always Occur Host-parasite relationship is dynamic: Sometimes it works out in favor of host; sometimes, the pathogen Many factors influence whether exposure to a pathogen will result in disease: a. Microbe is unable to multiply e. Health status of the host b. Microbe is unable to attach to receptors f. Immune status of the host c. Antimicrobials inhibit or destroy microbe g. Phagocytes engulf and destroy pathogen d. Microbial antagonism by normal flora II. Host Defense Mechanisms Host defense mechanisms – ways in which the body protects itself from infection and disease – can be thought of as an army consisting of three lines of defense. First line of defense: An elaborate defense network that prevents entry of microbes and other foreign materials. Second line of defense: Additional host defenses that are immediately summoned to prevent pathogens from becoming established in tissues. Third line of defense is specific, acquired, and requires activation. It involves the generation of antibodies and memory cells in response to the presence of a specific antigen. NOTE: The 2nd and 3rd lines of defense are involved in the immune response. Host Defense Mechanisms **Characteristics of Non-specific (Innate) Defenses** **Characteristics of Specific (Acquired) Defenses** Exists in all people, all the time Exists only in those who were previously exposed Active at the first, and all subsequent, exposures to a particular pathogen Protects against all microbes Requires activation Immediately called into action Active at the second, and all subsequent, KEY CONCEPT: Nonspecific defenses function the same exposures way regardless of the pathogen or # of exposures Protects against only one specific microbe 2 of 6 BI 127 Microbiology Chapter 17 Kate E. Kryger Innate Nonspecific Host Defenses Part III: The First Line of Defense I. Physical Barriers Cells, structures and/or forces that cover or line body surfaces → Make it difficult for microbes to enter the body A. Intact Skin Few pathogens can penetrate this barrier when intact Keratinized cells: The outermost layer of epithelial cells are compacted and cemented together, and are impregnated with keratin. The result is a thick, tough layer that is highly impervious and waterproof. Desquamation: sloughing of epidermal skin cells B. Mucous Membranes Mucus: Traps microbes and particles; and presents another physical barrier Cilia: Sweeps microbes (trapped in mucus) out of the respiratory passageways Hairs: Trap microbes C. Protective Forces Coughing & sneezing: Reflexively force microbes and other irritants from the respiratory passageways Blinking & tears: Flush bacteria from the conjunctiva Saliva: Traps microbes in the oral cavity and carries them to the stomach Vomiting & diarrhea: Evacuate the gastrointestinal tract Urine flow & voiding of bladder: The flow of urine flushes microbes out of the urinary tract II. Chemical Barriers Involve chemicals or molecules produced by the body that inhibit microbial growth 1. Sebum: Fatty acids are antimicrobial 2. Sweat: Salt can be antimicrobial 3. Gastric acid: Hydrochloric acid (HCl) – few organisms can survive pH 2 4. Lysozyme: An enzyme that cleaves peptidoglycan; it is present in tears, sweat, mucus and saliva 5. Lactoferrin: A protein in saliva, mucus and milk that binds iron so that only the host may use it, and the microbe cannot. III. Microbial Antagonism Microbial antagonism refers to the ability of the host’s normal flora to prevent pathogens from colonizing. Normal flora may inhibit growth of the foreign microbe by: a. Acting as another physical barrier b. Competing for available space & acting as another physical barrier c. Competing for nutrients d. Producing antibacterial factors that destroy the newly arrived pathogen Examples: Some residents in the large intestine secrete bacteriocins, which can inhibit or kill other bacteria Lactobacillus acidophilus in vagina 3 of 6 BI 127 Microbiology Chapter 17 Kate E. Kryger Innate Nonspecific Host Defenses Part IV: The Second Line of Defense I. Fever Hypothalamus regulates body temperature Normal body temperature: 98.6° F / 37° C Fever – a systemic increase in body temperature Oral temperature: > 99.5° F (>37.5° C) Rectal temperature: > 100.5° F (>38° C) Fever is a nearly universal sign of infection. It is also associated with certain allergies, cancers and other illnesses. How high does fever get? With infections, temperature rarely rises >104.5° F (>40.3° C). If temperature reaches ~107° F (41.5° C), brain damage can occur. A. How Does Fever Arise? Pyrogens, substances that cause fever, act on the hypothalamus to “increase” the internal thermostat Some come from outside sources (e.g., endotoxin, pathogens) Some come from inside the body (e.g., substances released by phagocytes) B. Benefits of Fever to the Host 1. Raises body temperature above the optimum temperature for growth of many pathogens RESULT: 2. Increases rate of chemical reactions associated with defense mechanisms RESULT: 3. Makes patient feel “ill” RESULT: C. Should a Fever Be Treated? Most suggest a slight-to-moderate fever should be allowed to run its course in an otherwise healthy person. High (>102° F) fevers should be treated immediately with antipyretic drugs. Antipyretic drugs lower the setting of the hypothalamic center and restores normal temperature. Examples: Aspirin or acetaminophen II. Inflammation The body normally responds to any local injury, irritation, microbial invasion or bacterial toxin by a complex series of events collectively referred to as inflammation (or inflammatory response). Without inflammation, infections would go unchecked and wounds would never heal. Inflammatory response is immediate: Begins within minutes; occurs within one hour. A. Major Events in Acute Inflammation 1. Release of chemical mediators 2. Vasodilation & ↑ permeability of capillaries → Plasma & proteins escape into surrounding tissue 3. Leukocytes accumulate at site of injury 4. Tissue repair & healing 4 of 6 BI 127 Microbiology Chapter 17 Kate E. Kryger Innate Nonspecific Host Defenses B. Characteristics of Inflammation Redness: Heat: Swelling: Pain: C. Purposes of Inflammation 1. Localize infection → Prevent spread of pathogens 2. Destroy and detoxify pathogens 3. Aid in tissue repair and healing D. Potential Harmful Effects of Inflammation The host’s immune responses to the invading microbes can themselves be the cause of tissue injury. Example: The inflammatory reaction to Mycobacterium tuberculosis sequesters the bacteria to prevent further infection. But, “side effects” of inflammation are fibrosis and damage to the tissue itself. III. Phagocytosis KEY IDEA: Inflammation and phagocytosis go hand-in-hand Phagocytosis is the process by which phagocytes engulf and ingest foreign material, including microbes. Of the five leukocytes, there are TWO main phagocytic cells: 1. Neutrophils (Polymorphonuclear leukocytes, PMNs) Granulocytes that circulate in the bloodstream Leave the circulation and migrate to site of inflammation/infection “First responders” in inflammation Short-lived (~3 day life span) → Tend to die after phagocytosis → Pus formation 2. Macrophages Develop from monocytes (that circulate in the bloodstream) Macrophages are fixed or wandering in tissues “Late responders” in inflammation Longer-lived (months/years life span) → Phagocytize and keep on going A. Migration to the site of inflammation/infection Chemotaxis: Directed migration to a particular site, in response to a chemical signal Chemokine: A substance that attracts or calls phagocytes B. Steps of Phagocytosis 1. Chemotaxis: Phagocytes are attracted to chemokines to the site where they are needed 2. Adherence: Phagocyte binds to specific molecules on microbe’s surface 3. Ingestion: Phagocyte engulfs microbe and takes it inside within a phagosome 4. Fusion of phagosome with lysosome, which contains digestive enzymes 5. Digestion: Microbe degraded by digestive enzymes (occurs within 20 min); debris is released outside the phagocyte 5 of 6 BI 127 Microbiology Chapter 17 Kate E. Kryger Innate Nonspecific Host Defenses IV. Interferons Interferons are small, viral defense proteins, produced by virus-infected host cells. o Interferon is synthesized and released by the infected cell. o Interferon then binds to surface of health neighboring cells. EFFECT: Health neighboring cells synthesize anti-viral proteins, which block viral replication. Virus- Healthy infected host cell host cell V. Complement (The Complement System) Named because the system “complements” the other immune responses Complement (C´) refers to a group of ~30 proteins found in the plasma These proteins interact with each other in a step-wise manner, known as a complement cascade A. Complement Activation Two ways to activate complement: 1. Antibodies bind to a microbe 2. Complex molecules on a microbe’s surface directly activates complement B. Beneficial Consequences of Complement Activation 1. Directly lyse bacteria & other foreign cells via membrane attack complexes Produce holes in cell membranes → Lysis 2. Initiates & amplifies inflammation 3. Attracts phagocytes Some C´ components are chemokines 4. Enhances phagocytosis through opsonization Opsonin – a substance (antibody or C´ component) binds to the surface of bacteria Phagocytes have receptors for opsonin → Bind to opsonin Phagocytes use opsonin as a “handle” to assist phagocytosis 6 of 6