1. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings M I C R O B I O L O G Y a n i n t r o d u c t i o n ninth edition TORTORA  FUNKE  CASE 16 Innate Immunity: Nonspecific Defenses of the Host

2. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Nonspecific Defenses of the Host  Susceptibility: Lack of resistance to a disease.  Immunity: Ability to ward off disease.  Innate immunity: Defenses against any pathogen.  Adaptive immunity: Immunity, resistance to a specific pathogen.

3. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Host Defenses Figure 16.1

4. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings First line of defense (Non-specific resistance)  Physical and Chemical Defenses  Normal Flora Second line of defense (Non-specific resistance)  Phagocytosis  Inflammation  Fever  Antimicrobial substances: Complement, Interferon Third line of defense (Specific Resistance)  Antibodies  B cells and T cells

5. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Physical Factors  Skin  Epidermis consists of tightly packed cells with  Keratin, a protective protein

6. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Physical Factors  Mucous membranes  Ciliary escalator: Microbes trapped in mucus are transported away from the lungs.  Lacrimal apparatus: Washes eye.  Saliva: Washes microbes off.  Urine: Flows out.  Vaginal secretions: Flow out. Figure 16.4a

7. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Chemical Factors  Fungistatic fatty acid in sebum.  Low pH (3-5) of skin.  Lysozyme in perspiration, tears, saliva, and tissue fluids.  Low pH (1.2-3.0) of gastric juice.  Transferrins in blood find iron.  NO inhibits ATP production.

8. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Normal Microbiota  Microbial antagonism/competitive exclusion: Normal microbiota compete with pathogens.

9. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Formed Elements in Blood Table 16.1 (1 of 2)

10. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Table 16.1 (2 of 2) Formed Elements in Blood

11. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Neutrophils60-70% Basophils0.5-1% Eosinophils2-4% Monocytes3-8% Lymphocytes20-25% Differential White Cell Count  Percentage of each type of white cell in a sample of 100 white blood cells.

12. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings White Blood Cells  Neutrophils: Phagocytic  Basophils: Produce histamine  Eosinophils: Toxic to parasites and some phagocytosis  Dendritic cells: Initiate adaptive immune response  Monocytes: Phagocytic as mature macrophages  Fixed macrophages in lungs, liver, and bronchi  Wandering macrophages roam tissues.  Lymphocytes: Involved in specific immunity. PLAY Animation: Host Defenses

13. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Toll-like receptors: What are some evolutionarily conserved features of microbes that our immune cells could recognize? Step 2. cytokines

14. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings The largest group of cytokines stimulates immune cell proliferation and differentiation. This group includes Interleukin 1 (IL-1), which activates T cells; IL-2, which stimulates proliferation of antigen-activated T and B cells; IL-4, IL-5, and IL- 6, which stimulate proliferation and differentiation of B cells; Interferon gamma (IFN  ), which activates macrophages; and IL-3, IL-7 and Granulocyte Monocyte Colony-Stimulating Factor (GM-CSF), which stimulate hematopoiesis.

15. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Phagocytosis  Phago: from Greek, meaning eat  Cyte: from Greek, meaning cell  Ingestion of microbes or particles by a cell, performed by phagocytes. Figure 16.6

16. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Phagocytosis Figure 16.7

17. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Inhibit adherence: M protein, capsules Streptococcus pyogenes, S. pneumoniae Kill phagocytes: LeukocidinsStaphylococcus aureus Lyse phagocytes: Membrane attack complex Listeriamonocytogenes Escape phagosomeShigella Prevent phagosome-lysosome fusion HIV Survive in phagolysosomeCoxiella burnetti Microbial Evasion of Phagocytosis PLAY Animation: Phagocytosis

18. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Inflammation  Redness  Pain  Heat  Swelling (edema)  Acute-phase proteins activated (complement, cytokine, and kinins)  Vasodilation (histamine, kinins, prostaglandins, and leukotrienes)  Margination and emigration of WBCs  Tissue repair

19. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings HistamineVasodilation, increased permeability of blood vessels KininsVasodilation, increased permeability of blood vessels ProstaglandinsIntensity histamine and kinin effect LeukotrienesIncreased permeability of blood vessels, phagocytic attachment Chemicals Released by Damaged Cells

20. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Inflammation Figure 16.8a–b

21. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Inflammation PLAY Animation: Inflammation Figure 16.8c–d

22. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings The movement of phagocytes in the direction of an infection, due to attraction by complement, chemicals released by microorganisms, and the remnants of damaged cell membranes is a process called A) phagocytosis. B) chemotaxis. C) diapedesis. D) cyto adherence.

23. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Fever: Abnormally High Body Temperature  Hypothalamus normally set at 37°C.  Gram-negative endotoxins (so-called pyrogens) cause phagocytes to release interleukin–1 (IL–1)  Hypothalamus releases prostaglandins that reset the hypothalamus to a high temperature.  Body increases rate of metabolism and shivering which raise temperature.  When IL–1 is eliminated, body temperature falls (crisis).

24. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings  Hypothalamus controls body temp  Pyrogens resets temp set point  Pyrogens: cytokines; LPS  Unfavourable for bacterial replication  Favourable for immune response--phagocytosis; lymphocyte replication etc FEVER

25. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings The Complement System  Serum proteins activated in a cascade. Figure 16.9

26. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings The Complement System  Activated in 3 ways  Antibody-antigen (augments specific defense)  Molecules that recognize bacterial sugar polymer (mannan)  “Random binding” to cell surfaces (C3b)  Triggers a cascade  3 effects

27. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Effects of Complement Activation  Opsonization or immune adherence: Enhanced phagocytosis.  Membrane attack complex: Cytolysis.  Attract phagocytes. Figure 16.10

28. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Effects of complement system 1. Opsonization

29. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings 2. Membrane Attack Complex (Lysis) Are G+ or G-ve cells more susceptible to killing by MAC? Why?

30. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings 3. Inflammation  What else triggers inflammation? Tissue damage  What are features of inflammation?  What is the inflammatory process?

31. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Effects of Complement Activation Figure 16.11

32. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Some Bacteria Evade Complement  Capsules prevent C activation.  Surface lipid-carbohydrates prevent MAC formation.  Enzymatic digestion of C5a. PLAY Animation: The Complement System

33. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Interferons (IFNs)  Alpha IFN and Beta IFN: Cause cells to produce antiviral proteins that inhibit viral replication.  Gamma IFN: Causes neutrophils and macrophages to phagocytize bacteria.

34. Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings Interferon and viral infections: a protective alerting system