Micro320: Infectious Disease & Defense. Microbio320 Website. Life Expectancy in the USA. Lecture #2: Introduction/ Overview.

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1 Lecture #2: Introduction/ Overview Innate Immunity Micro320: Infectious Disease & Defense Instructor: Michele Klingbeil Microbio320 Website Life Expectancy in the USA

2 World Life Expectancy Jan 18, World Life Expectancy Jan 18, 2011 World Life Expectancy Jan 18, 2011

3 Worldwide causes of death, 2005 Infectious Disease Mortality, (CDC) Deaths from infectious diseases fell in the United States during the 20th century. The spike shows the 1918 influenza pandemic, which killed more than 20 million people, including about 500,000 Americans Some Some reasons Reasons for increased for Life Life Expectancy Vaccination Antibiotics Improved sanitation Improved hygiene Better health care Decreased Infant mortality rate Decrease in unhealthy behaviors Nutrition

4 Aristotle: Living things can come from nonliving things - spontaneous generation. It was common knowledge that Review of Germ Theory simple organisms like worms, beetles, frogs, and salamanders could come from dust, mud, etc., and food left out, quickly swarmed with life Jean Baptist Van Helmont ( ): mice come from dirty rags/ rotting grains Francisco Redi ( ): challenged the idea of spontaneous generation, setting up the 'meat/maggot' experiment. Anton van Leeuwenhoek: first person to make a single-lens microscope & observe microbes Louis Pasteur: disproved spontaneous generation once and for all. History of Microscopy Robert Hook Developed microscope with 30x magnification Anton van Leeuwenhoek Began grinding lenses First descriptions bacteria, protozoa and spermatozoa animalcules Series of letters to Royal Society of London Whole new world Rain water, canal water, saliva, his own feces Modern day reconstruction - Al Shinn Pasteur s Experiment

5 Germ Theory Infectious Agents The germ theory of disease, also called the pathogenic theory of medicine, is a theory that proposes that microorganisms are the cause of many diseases An infectious disease is one in which detrimental changes in the health of the host occurs as a result of damage caused by a pathogenic organism It wasn't until 1876 that a microbe was definitively proven to cause disease Robert Koch showed that Bacillus anthracis caused anthrax. Koch used a set of criteria to demonstrate that the specific cause (etiology) was a microbe Koch s Postulates The suspected pathogen must always be found in diseased individuals, but absent in a healthy individual The pathogen must be isolated from the diseased individual and grown in a pure culture The pathogen from the pure cultures must cause the disease when inoculated into a healthy, susceptible host The same pathogen must be reisolated from the host that was inoculated with the pure culture What is Immunology The study of the body's immune system and its functions and disorders. The study of the body's natural defense mechanisms against disease. The branch of medicine that studies the immune system, immunity, and allergies. The branch of medicine that is concerned with the structure and function of the immune system and laboratory techniques involving the interaction of antigens with specific antibodies.

6 Lecture Objectives At the end of this lecture you should be able to: Describe the basic components of the immune system Describe components of non-specific immunity Describe the roles of anatomical barriers Describe the roles of Cellular components Describe the roles of Humoral components We will add to this base of knowledge with detailed mechanisms It is always about a Balance! Infection Immunity Disease = Bolus of infection x virulence immunity It is always about a Balance! Infection Immunity Disease = Bolus of infection x virulence immunity

7 Overview: Non-specific & Specific Defenses Immunity latin immunitas Immune SYSTEM - layered and interactive network must distinguish self from non-self Non-specific Resistance Innate Immune System (Not antigen specific no memory) Specific Resistance Adaptive Immune system (Antigen specific memory) Overview: Non-specific & Specific Defenses Innate: 1 st line of defense Adaptive defense Overview: Non-specific & Specific Defenses

8 Overview: Non-specific & Specific Defenses Summary of Non-specific Defenses Anatomic Barriers Physiologic Barriers Phagocytic Barriers Inflammatory Barriers Innate Immunity Barriers

9 Anatomical Barriers What Happens to All That Skin? A scanning electron micrograph of a section of skin. Epidermal cells are dead, dry, and slough off, providing an effective barrier to most microorganisms. ~10 billion skin cells per day, or 250 grams (about half a pound) of skin is shed by the average person every year! 2008 Pearson Education, Inc., publishing as Benjamin Cummings Anatomic Barriers Location of Surface Epithelial Barriers

10 Respiratory Epithelium Barrier Respiratory Epithelium 1 cilia 2 mucus cell Nature Reviews Immunology 5, (January 2005) Immunoregulatory functions of surfactant proteins Respiratory Epithelium Barrier August 28, 2009 airway epithelia contain a system in which motile cilia sense a noxious substance and initiate a defensive mechanism to eliminate the compound. Anatomical Barriers Chemical Factors System or Organ Component Mechanism Skin Sweat Anti-microbial fatty acids Mucous Membranes HCl (parietal cells) Tears and saliva Defensins (respiratory & GI tract) Sufactants (lung) Low ph Lysozyme and phospholipase A Antimicrobial Opsonin

11 Humoral Components Component Complement Coagulation system Lactoferrin and transferrin Lysozyme Cytokines Mechanism Lysis of bacteria and some viruses Opsonin Increase in vascular permeability Recruitment and activation of phagocytic cells Increase vascular permeability Recruitment of phagocytic cells Β-lysin from platelets a cationic detergent Compete with bacteria for iron Breaks down bacterial cell walls Various effects Innate System Cellular Components Non-functional will post on website! Innate System Cellular Components 2008 Pearson Education, Inc., publishing as Benjamin Cummings

12 Immune Cell Development - Hematopoeisis Bone marrow Self-renewing The Phagocytic System The mononuclear phagocytic system is considered a functional system because it is composed of cells, located in many body systems, that share a common function: phagocytizing invaders. Professional phagocytes 2008 Pearson Education, Inc., publishing as Benjamin Cummings Five Major Events of Phagocytosis Chemotaxis Adherence Ingestion Killing Elimination 2008 Pearson Education, Inc., publishing as Benjamin Cummings

13 Macrophages & Inflammation Respiratory Burst Oxygen-Dependent Myeloperoxidase-Independent Reactions Glucose +NADP + G-6-P-dehydrogenase Pentose-P + NADPH NADPH + O 2 NADPH oxidase Cytochrome b558 NADP + + O 2-2O H + Superoxide dismutase H 2 O O 2 2O H 2 O 2 OH* + OH O 2 Toxic compounds Superoxide anion (O 2 - ), Hydrogen peroxide (H 2 O 2 ), Singlet oxygen ( 1 O 2 ) and Hydroxyl radical (OH*) Respiratory Burst Oxygen-Dependent Myeloperoxidase-Dependent Reactions H 2 O 2 + Cl - 2OCl - + H 2 O myeloperoxidase OCl - + H 2 O 1 O 2 + Cl - + H 2 O Toxic compounds Hypochlorous acid (OCl - ), and Singlet oxygen ( 1 O 2 )

14 Respiratory Burst Detoxification Reactions 2O H + 2 H 2 O 2 Superoxide dismutase Catalase H 2 O 2 + O 2 H 2 O + O 2 O 2 -Independent Killing in Phagolysosome Effector Molecule Cationic proteins (cathepsin) Lysozyme Lactoferrin Function Damage to microbial membranes Hydrolyses mucopeptides in the cell wall Deprives pathogens of iron Hydrolytic enzymes (proteases) Digests killed organisms Summary of Intracellular Killing Intracellular Killing Oxygen Dependent Oxygen Independent Myleoperoxidase Dependent Myleoperoxidase Independent