2. Passive Defenses: the boundaries  mechanical properties (fur, skin, mucosae)  rinsing/flooding  chemical properties o skin: oil, sweat, psoriasin o stomach: acid o Intestine: deoxycholate, lysozyme, defensins  normal, bacterial flora

4. E.coli adhering to particular epithelial cells of the urinary tract.

6. Psoriasin: anti-bacterial protein of the skin specific for E. coli (gram- negatives)

8. Lactobacillus sp.

10. Acute Inflammatory Response 1.Mobilization of active defenses  Vasodilation  Vascular permeability  neutrophils 2.Initiating the adaptive responses.

12. INVASION Tissue damage Pathogens Clotting System (Hageman Factor) Kinin/ Bradykinin Complement cascade Vasodilation Permeability Neutrophils Macrophages Dendritic cells Basophils/ Mast cells Lipid mediators Cytokines Chemokines

13. Cyclooxygenase Lipoxygenase LeukotrienesProstaglandins

15. Vasodilation and increased vascular permeability leads to fluid leakage (edema) and extravasation of neutrophils.

19. Pathogen Pattern Recognition Receptors (PPRR) Bind Pathogen Associated Molecular Pattern (PAMP) molecules. 1.MBP and C-RP are soluble PPRR 2.TLR and LPS-BP are membrane-bound PPRR 3.NLR (Nod-like receptor) and RLH (Rig-like Helicase) are cytoplasmic PPRR

20. Toll deficiency and loss of drosomycin

22. Bruce A. Beutler. Identification of LPS receptor is TLR 4. (Science 1998). Jules A. Hoffman The Drosophila gene Toll confers anti-fungal defense (Science 1996) Ralph M. Steinman Discovers dendritic cells in 1973. Nobel price Physiology 2011.

23. Ralph M. Steinman.

24. Dendritic Cells Ralph Steinman & Zanvil A. Cohn (1973) J. Exp. Med.

25. Phase contrast micrograph of spleen cells after 2 days in culture. Four dendritic cells (arrows) can be seen clustered with lymphocytes. (Courtesy of Ralph Steinman from K. Inaba et al., J. Exp. Med. 160:858, 1984.)

26. Ruslan Medzhitov (overlooked by 2011 Nobel?)

31. Bubonic plague (Yersinia pestis)

33. Yersinia pestis

34. Y. Pestis in blood smear: bipolar, safety pin staining. Yersinia escape detection by the innate defenses because at 37 C: -Y. pestis produces an LPS that poorly activates TLR-4. -Y. enterocolitica no longer produces flagella.

35. Legionnaire’s disease: (bilateral, basal, infiltration)

36. Legionella pneumophilia: TLR5 mutants, not recognizing flagelin, increase susceptibility

73. Elie Metchnikoff (1845-1916),

75. Phagocytosis E. coli by macrophages.

78. confocal microscopy demonstrating bacteria internalised by a mammalian cell Phagocytosis

79. Streptococcus faecalis.

80. Streptococcus pneumoniae.

84. Opsonization.

86. Zipper-Model.

90. Chediak-Higashi Syndrome

95. NADPH+H + NADP + Glucose 6 CO 2 MPO Lysosome O2O2 O2-O2- H2O2H2O2 Pathogen Oxygen burst neutrophils Oxidase HM S

96. gp91 p22 Cyt b558 gp91 p22 gp91 p22 Rac-2 GTP Rac-2 GTP p67 P67 NOXA p47 P47 NOXO P P Rac-2 GDP +P NADP + NADPH+H + GEF O2O2 O2-O2- Membrane Heme NOX-Organizer NOX-Activator

97. Nitric oxide synthase Possible oxidant- generating reactions of stimulated PMNs

102. Ribbon diagram of human defensin. Numbers indicate the position of the cysteine residues; disulphide bonds are shown in yellow. The defensin dimer is stabilized by multiple hydrogen bonds and hydrophobic interactions at the monomer-monomer interface. The top of the dimer is polar; the base is apolar.

103. Rat peritoneal neutrophils, which often contain ringed nuclei are stained (antibody) for the presence of defensins. Defensins (blue) are present in the cytoplasm and have a granular distribution.