1.  Immune System Topics in Human Pathophysiology Fall 2011 Gilead Drug Safety and Public Health

2. Outline  Lymphatic and Immune System  Lymphatic System  White Blood Cells  Innate Defenses  First Line Defenses  Second Line Defenses  Adaptive Defenses (Third Line Defenses)  Pathophysiology of Immune System

3. Figure 9.3a

4. Lymphatic System  Functions:  Drains excess tissue fluid (interstitial fluid)  Transports fats and fat-soluble vitamins absorbed from digestive system  Defends against infection

5. Figure 9.3b Pathway of Fluid

6. White Blood Cells

7. First Line of Defense  Skin – barrier, sloughs, acidic pH  Tears- Lubricate and wash eye, contain lysozyme  Saliva - Lubricates and rinses teeth, contains lysozyme  Earwax – waterproof, prevents water (and bacteria) entry  Digestive acids – kills pathogens that enter stomach

8. First Line of Defense  Mucus – traps pathogens for WBCs to kill, cilia sweeps  Vomiting – removes toxins and pathogens from stomach  Urination – slightly acidic, cleanses urinary tract  Defecation – removes bacteria from GI tract  Resident bacteria – outcompete harmful organisms

10. Second Line of Defense (Nonspecific)  Phagocytosis  Inflammatory response  Interferons  Natural killer cells  Fever

11. Phagocytosis and antigen presentation Figure 9.6a

12. Figure 9.7 Inflammation Link

13. Figure 21.5 Interferon

14. Third Line of Defense (Specific Immunity)  B cells and T cells  B lymphocytes (B cells)  Mature in bone marrow, responsible for antibody mediated immunity  When they recognize a pathogen (antigen) and are activated, develop into plasma cells and memory cells  Plasma cells produce 1000s of antibodies (immunoglobulins) per second

15. B lymphocytes Recognition Activation Attack (cloning and antibody production)

16. Figure 21.14 Antibody functions

17. Third Line of Defense (Specific Immunity)  T lymphocytes  3 types: helper T cells, cytotoxic T cells, suppressor T cells  When recognize a pathogen and are activated, these attack the pathogen and create a cadre of memory cells

18. Figure 9.13

19. Figure 21.17 Helper T cells are presented with antigen by specialized WBCs When activated these helper T cells clone themselves into memory cells and active cells

20. Cytotoxic T cells  AKA killer T cells  Recognize pathogen (antigens) in virally infected cell or cancer cells  Activated by cytokines from helper T cells  “Clone” themselves into attack cells and memory cells  Attack by producing proteins that open holes in infected cells

21. Figure 21.19

22. Immunologic Memory  Memory cells circulate, sometimes for a lifetime, scanning for that pathogen they recognize  A second infection by the same pathogen will yield a stronger, faster immune response that prevents illness

23. Figure 9.15

24. Immune System Pathophysiology  Allergies  Autoimmune disorders  Immunodeficiencies

25. HIV Pathophysiology  A retrovirus that infects host cells macrophages and helper T cells  Its RNA is reverse transcribed into DNA, then inserted into host chromosomes and lays dormant, sometimes for years  Some trigger will cause the viral genome to be expressed and new virus is made  New virus erupts from WBCs, killing them and infecting other WBCs until the levels are dangerously low

26. Time Course of HIV infection and disease link

27. Gilead therapies against infectious agents

28.  Figure 9.19

29.  Figure 9.20 Reverse transcriptase required Protease required

30. Figure 9.20 Reverse transcriptase Inhibitors work here Protease inhibitors work here