Innate Immunity

1. Innate Immunity Component of the Innate Immunity Christopher Moyer, Taylor Smith, Stefano D’Asti, Hyeon (Harry) Kang PHM142 Fall 2014 Instructor: Dr. Jeffrey Henderson

2. What is Innate Immunity? • Innate Immunity – Also Known as non-specific immunity, is a division of the immune system. • It deals with pathogens in a non-specific manner. • These include: • Barriers (Skin, Nails, Mucous) • Inflammation • Cells (Macrophages, Dendritic, Natural Killer, Mast) • Complement System

3. Anatomical barriers to infections There are three main anatomical barrier to infections, including mechanical factors, chemical factors, and biological factors. These barriers are our first line of defence against external pathogens.

4. Mechanical Factors • Skin • A physical barrier preventing pathogens from entering the body • When damaged, provides an easy path of entry into the body • Cilia • Exist in the lungs and respiratory tract • Beat periodically, pushing pathogens out of the lungs

5. Chemical Factors • Sweat • Fatty acids and low pH in sweat prevent the growth of certain bacteria • Tears, Saliva, Mucus • Lysozyme and phospholipase found in tears, saliva and mucus can break down the cell wall of bacteria and destabilize their membranes • Surfactants • Surfactants in the lungs act as opsonins, which promote the phagocytosis of bacteria • Defensins • Defensins found in the lung and digestive tract are low molecular weight proteins which have antimicrobial factors

6. Biological Factors • The existing flora of the skin and gastrointestinal tract secrete toxins which prevent the growth of invading pathogens • The existing flora compete with the invading pathogens for space and nutrients

7. Inflammation • Is a biological response by the body to protect itself • Inflammation caused by pathogens or sterile factors (same response different causes) • Chemicals initiate the response • Chronic and Acute inflammation

8. Acute inflammation • Occurs over a short period of time • Induced Effects of Acute inflammation are: • Redness • Pain • Heat • Swelling • Loss of function • Pathogen removal by leukocytes http://www.uic.edu/classes/bios/bios100/lecturesf04am/lect23.htm

9. Chronic Inflammation • Occurs over a long period of time • Caused by persistent injury, exposure to toxic substances, and auto-immune diseases • Leukocyte infiltration • Destruction of cells • Fibrosis and angiogenesis

10. Drug therapies • NSAIDs • Anti-histamines http://pharmacyinformatics.wikispaces.com/Antihistamines

11. Complement System • A sub-division of the innate immune system that ‘primes’ or ‘complements’ the phagocytic cells and antibodies for more efficient neutralization. • Complement System consists of proteases that cleaves specific proteins to release factors that allow for further cleavage, ultimately resulting in death of the pathogen.

12. Complement System Function • The Complement system has four main functions: • Opsonization – Phagocytosis of pathogen  • Chemotaxis – Attracting cells (Neutro, Macro) • Cell Lysis – Lysis of pathogenic cell (FOCUS) • Aggregation – pathogenic cell clumping 

13. Three (3) Pathways of the Complement System • Classical Pathway • Relies on pathogen binding antibodies • Alternative Pathway • Does not rely on pathogen binding antibodies • Lectin Pathway • Relies on pathogen binding antibodies • Homologous to the Classical Pathway, except Mannose Binding Lectin (MBL) instead of C1q. • Ultimately, they all achieve the four functions of the complement system. • MAC (Membrane Attack Complex)

14. MEMBRANE ATTACK COMPLEX (pokes holes in the pathogens, killing them) http://en.wikipedia.org/wiki/Complement_system#mediaviewer/File:Complement-pathways.png

15. Cells • Mast Cells (allergy and wound healing) • Phagocytes (Eat pathogens) • Macrophages (Engulf and send chemokines) • Granulocytes (contain toxic granules) • Dendritic Cells (Barrier phagocytes) • Natural killer cells (kill infected cells)

16. Mast Cells • Recognition: IgE released by lymphocytes • Granulocyte contents • Prostaglandins, cytokines, leukotrines • Histamine • Proteases

17. Phagocytes • Recognition Pattern Receptors • Lysosomes • ROI • Cytokines

18. Natural Killer Cells • Recognition • Stressed Cells • DNA damage • Tumour • Microbial infection

19. Summary Slide • There are three main anatomical barrier to infections, including mechanical factors, chemical factors, and biological factors. These barriers are our first line of defence against external pathogens. • Complement system “complements” the immune system by various means, ultimately leading to the efficient and swift death of the pathogenic cells (and pathogens) • The body contains many cell responses to pathogens such as mast cells, phagocytes and natural killer cells. Each use their own or share mechanisms such as ROI, cytokines or receptor activation. • Inflammation • Occurs when cells are damaged by pathogens or other sterile factors • Damaged cells release a variety of chemicals to cause the cardinal signs of inflammation and to attract specialized cells • Some anti-inflammatory drugs include NSAIDs and Antihistamines (4 receptors)

20. References • Ward P. & Sarma J. 2010. The complement system. Cell and Tissue Research 343: 227 – 235 http://link.springer.com/article/10.1007/s00441-010-1034-0 • Leurs R., Vischer H. F., WijtmansIwan M., de Esch J.P. Trends in Pharmacological Sciences, April 2011, Vol. 32, No. 4. • Chen G. Y.  and Nuñez G. Nat Rev Immunol. Dec 2010; 10(12): 826–837. • The immune system. http://www.uic.edu/classes/bios/bios100/lecturesf04am/lect23.htm • Beck S., Acute and Chronic Inflammation. http://www.hopkinsmedicine.org/mcp/Education/300.713%20Lectures/300.713%202013/Beck_08.26.2013.pdf • Brown G. 2011. Innate antifungal immunity: the key role of phagocytes. Annu Rev Immunol 29:1-21. • Payne V & Kam P. 2004. Mast cell tryptase: a review of its physiology and clinical significance. Anaesthesia 59:695-703. • Jost S & Altfeld M. 2013. Control of human viral infections by natural killer cells. Annu Rev Immunol 31:163-94.