Innate Immunity & Inflammation

1. Innate Immunity & Inflammation Dr. M. Izad Oct 2014

2. Objectives • Innate immunity • Physical barriers • Chemical barriers • Cellular Barriers • Connections between innate & adaptive immunity • Inflammation

3. Innate & Adaptive Immunity

4. Mucus & Mechanical factors • Commensal flora (infection by Candida spp, Clastridiuumdifficile) • PH chenges (Production of glycogen by the epithelium in the vagina)

5. Skin

6. Psoriasin prevents colonization of skin by E. Coli

7. Effectors of Innate Immune Responses to Infection

8. Some antimicrobial peptides • Membrane disruption • Inhibiting the synthesis of DNA, RNA or proteins • Activating antimicrobial enzymes • Staphylococcus aureus • Streptococcus pneumoniae • E.Coli • Pseudomonas aeruginosa • Hemophilus influenzae • Fungi • Viruses

10. Structure, Location, and Specificities of TLRs Fig. 4-2

13. Signaling functions of TLRs (2) Fig. 4-3 B

15. Innate Immune System Cells

16. The major Leukocytes of Innate Immunity

19. Killing Mechanism in Leukocytes Oxidative Reactive Oxygen Species (ROS) (NADPH phagosomeoxidase/ Phox) Reactive Nitrogen Species (RNS) Non oxidative Fusion of neutrophil granules with phagosomes Antimicrobial peptides (defensins & cathelicidins) Antimicrobial proteins (BPI: bactericidal/ permeability increasing protein) Enzymes (proteases & lysozyme)

21. Respiratory burst

22. TLR Bacteria Fungi protozoa

23. NK Cells Kill Injured and Infected Cells Fig. 4-8 A

24. Natural Killer (NK) cells provide a first line of defense against viral infection

25. Activating and Inhibitory NK Cell Receptors (1) Fig. 4-6A

26. Activating and Inhibitory NK Cell Receptors (2) Fig. 4-6B

27. Activating and Inhibitory NK Cell Receptors (3) Fig. 4-6C

28. NK Cells Activate Macrophages Fig. 4-8 B

29. Dendritic cells (DC) As agents of innate immunity, immature dendritic cells use a variety of PRRs (TLRs) to recognize pathogens. Provide a link between innate & adaptive immunity. Are able to generate ROS, NO & antimicrobial peptides. Plasmacytoid DCs are potent producers of type I interferons.

30. Inflammation Acute/Chronic Inflammation is a physiological response to a variaty of stimuli such as infections and tissue injury.

31. Hallmarks of Inflammation • Increasing of vascular permeability • Swelling (edema) • vasodilation • Redness • Heat • extravasation • Pain • Loss of function

32. Recruitment of macrophages & antimicrobial agents from the bloodstream in an inflammation response

37. Slow Reacting Substance of Anaphylaxis

39. Systemic Acute-phase Response

41. Chronic Inflammation develops when Antigen persists the accumulation & activation of macrophages is the hallmark of chronic inflammation. Fibrosis Granuloma (giant cells, epitheloid cells)

42. Activity of IFN-γ

43. Quiz • …….یکپروتئینضدمیکروبیاستکهبرایتشخیصبیماریهایالتهابیرودهبهکارگرفتهمیشود. • ………آنزیمیاستدرغشاءسلولهایفاگوسیتکهشروعکنندهتولید…………است.