Understanding Innate Immunity: Your Body's First Line of Defense

PHM142 Fall 2012 Instructor: Dr. Jeffrey Henderson Innate Immunity PHM 142 Oct 5, 2012 Jiangrui (Alice)Xu Deepinder Randhawa Sanaa Javed Stuti Shah

Overview • What is Innate Immunity? • Innate vs. Adaptive Immunity • External defense • Activation of internal defense • Internal defense mechanisms: -Fever -Phagocytes -NK Cells (Immunological Surveillance) -Interferons -Complement system

What is Innate Immunity? • Genetically determined • First line of defense against invasion by pathogens • Non-specific

Innate vs. Adaptive Immunity Microbiology and Immunology On-line, University of South Carolina School of Medicine

External Defenses: Anatomical barriers 1. Mechanical factor • Physical barrier of epithelial (eg. skin, mucous layer of respiratory/G.I tract) 2. Chemical factor • Chemical secretion of special glands (eg. sweat, lysozymes, tears, saliva, gastric juice) 3. Biological factor • Normal flora (eg. skin, G.I., vagina)

Body Temperature • 37 ⁰C • Regulated by thermoregulatory control centre (“thermostat”) in hypothalamus

Internal defense: Fever Molecular markers (i.e. endotoxin Toll-like receptor FOREIGN INVASION!! Host defence cell (i.e. macrophage) Pathogen (i.e. Gm–ve Bacteria) Pyrogen (Cytokines) Thermostat reset upward • Fever • Sleepiness • plasma [Iron] • Inhibit pathogens • Increase metabolic rate • Mobilize defenses at the site • Faster repair Activate cells of adaptive immune system (i.e. B lymphocytes)

Internal defense: Phagocytes First line of cellular defense against pathogenic invasion “janitorial and police services” Two general classes in humans: 1) Microphages Neutrophils – abundant, mobile, cellular debris + invading bacteria Eosinophils – less abundant, target foreign compounds coated with antibodies.

2) Macrophages Large, actively phagocytic cells Fixed: permanent residents Target must diffuse or move until within range Free: “wandering”, travel throughout body Arrive at the site of injury by migrating

Internal defense: Natural Killer cells Natural Killer (NK) cells are responsible for recognizing and destroying abnormal cells when they appear in tissues. How? abnormal cells have antigens not normally found on normal cells Not very selective Very rapid Highly versatile

NK cells activation KILL ME KILL ME KILL ME

Internal Defense: Interferons Small proteins Inhibit viral protein replication • Three types • Alpha • Beta • Gamma Innate (non-specific) immunity, Tutorvista

Internal Defense: Complement System • “Complements” the actions of antibodies • Cascade chain reaction • Classical pathway • Alternative pathway • Lectin pathway

Outcomes of Complement System • Stimulates inflammation • Attracts phagocytes • Opsonisation: opsonins make it easier for pathogens to be engulfed by binding to them • Membrane attack complex (MAC) in the presence of the activated C3b

Summary

References Agarwal, Vikas. "Innate Immunity." Indian Journal of Rheumatology 5.3 (2010): 131-36. Print Fox, Stuart Ira. Human Physiology. 10th ed. New York, NY: McGaw Hill, 2008. Print Martini, Frederic and Nath, Judi. Fundamentals of Anatomy and Physiology. San Fransisco, CA. Pearson Education Inc, 2009. Print "Innate Immunity." Innate Immunity. N.p., 16 Apr. 2011. Web. 22 Sept. 2012. <http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/I/Innate.html>. Mayer, Gene, Ph.D. "Innate (non-specific) Immunity." Innate or Non-specific Immunity. University of South Carolina, School of Medicine, 4 May 2011. Web. 21 Sept. 2012. <http://pathmicro.med.sc.edu/ghaffar/innate.htm>. Racaniello, Vincent. "Innate Immune Defenses." Innate Immune Defenses. N.p., 3 June 2009. Web. 27 Sept. 2012. <http://www.virology.ws/2009/06/03/innate-immune-defenses/>.

Thank you!

Understanding Innate Immunity: Your Body's First Line of Defense