Immune System Part II: The Innate Immune System

1. Immune System Part II: The Innate Immune System

2. Devastation Caused by Pathogens • Influenza epidemic 1918-1919 Killed 22 million people in 18 months. • Three million people will die from malaria this year. • Since 1980, over 619,000 people have died from AIDS in the U.S. • Ever seen Contagion?

3. Overview of the Immune System Parts of the Immune System • Innate Immunity • Barrier Defenses • Cellular Response • Chemical Response • Adaptive Immunity • Cell Mediated Response • Humoral Response 3

4. First Line of Defense Innate Immunity (Nonspecific Immunity) Innate Immunity-Activated immediately upon exposure to pathogen and is the same response for each exposure. First line of Defense: Integument System- • Skin and mucous membranes provide a physical barrier to entry of pathogens. Skin contains keratin, a structural protein that helps form that barrier. Mucus helps trap pathogens. • Skin's fatty acids and secretion from tears, sweat and oil glands are toxic to bacteria. • Natural bacterial fauna can outcompete many pathogen. 4

5. Body Passages and Innate Immunity • Trachea lined with ciliated cells and cells that secrete mucus. • Esophagus leads to stomach with a pH of 1-2 (acidic) which kills most pathogens • Urinary tract has lower pH (again acidic) and is flushed with urine. • Tear ducts with lysozymes. • Reproductive tract also has a lower pH (acidic once more). 5

6. Second Line of DefensePhagocytes and the Chemicals Released • Second Line of Defense-Activation of phagocytes (leukocytes/white blood cells) • Made in the red bone marrow. • Found in connective tissue, tissue lining organs, lymph nodes and circulating in the blood.

7. Neutrophils and Eosinophils • Neutrophils- are the first to arrive; numerous (1 billion made each day); survive only a few days. These are expendable cells. • Eosinophils- are weakly phagocytic cells that kill invaders that are clumped together. They also destroy parasitic worms.

8. Basophils and Mast Cells Basophils and mast cells are leukocytes in nearby connective tissue which produce histamines which are released when these cells are damaged. 8

9. Monocytes and Macrophages Monocytes-are transformed into large macrophages involved in phagocytosis and also important in the adaptive immune response as an antigen presenting cell. 9

10. Dendritic CellsKing of the Immune System • Dendritic cells (DC) are found in skin, nasal passages, intestines, spleen and throat. - Population numbers are smaller than other phagocytes.

11. Dendritic Cells • Dendritic cells are important in adaptive immunity as an antigen presenting cell

12. Phagocytes and TLR Receptors • Phagocytes have Toll-like-receptors (TLR) which recognize signature molecules. • The phagocyte engulfs the pathogens within a vesicle and deactivates or kills the pathogen. • Phagocytes can eat themselves to death.

13. Natural Killer Cell (not a phagocyte) • Natural killer cells can detect infected cells and cancerous cells due to changes in plasma proteins of the cells. • They secrete chemicals into the infected cells and kill them or puncture the infected cell’s membrane. 13

14. Natural Killer Cells Animation

15. Phagocytes and Chemical Response • Phagocytes can also activate chemical responses like the inflammatory response and the production of antimicrobial peptides.

16. Chemical Responses • Kinins or chemokines (microbial peptides) are released by certain phagocytes. • These molecules increase circulation and capillary permeability. • Attract leukocytes to site of injury • Affect nerve cells making area tender 16

17. Complement Proteins and the Killer Instinct 2. Complement proteins (approx. 30 proteins) work by a number of different methods. • These proteins create pores in invading bacteria, causing water to rush in. 17

18. Complement Proteins

19. Complement Proteins

20. Complement Proteins Forming Pores 20

21. Complement Proteins and Opsonizaton Complement proteins along with antibodies will coat a bacterium. Phagocytes recognize both the complement proteins and the antibody. Phagocytes will engulf the pathogen and destroy it. 21

22. Interferons 3. Interferons are proteins made by virus-infected cells. They are secreted and transported to neighboring cells to prevent viral infection from the infected cell. 22

23. Histamine Release and Inflammatory Response 4. Histamine is released by mast cells and basophil cells which are attracted to an injury site. When the skin is penetrated, cells are ruptured releasing chemical signals to attract the mast and basophil cells. These cells release histamine. 23

24. Inflammatory Response • Increases capillary permeability. The area becomes swollen, red, temperature increases from the increased blood flow. • Phagocytes leave the capillary bed because they are attracted histamine and other signals. • Phagocytes clean up pathogens and cell debris. 24

25. Homeostasis and Inflammatory Response • Inflammation continues as long as the triggers (pathogens) are present. • When phagocytes complete their job by removing the pathogens, macrophages begin to secrete substances that- • Suppress inflammation • Promote tissue repair 25

26. Fever • Inflammatory response is often accompanied by fever. • Some cytokines stimulate the brain to make prostaglandins. These prostaglandins stimulate the hypothalamus to a new temperature set point. The signals the hypothalamus sends out then: • Constrict blood vessels in the skin • Contract skeletal muscles • Increase heart rate and respiration 26