Innate (Nonspecific) Immunity

1. Innate (Nonspecific) Immunity

2. Overview of the Immune System Interactions between the two systems

3. No memory Innate Immunity Adaptive Immunity Comparisonof Innate and Adaptive Immunity • No time lag • A lag period • Not antigen specific • Antigen specific • Development of memory

4. Cells of the Immune System

6. Development of the Immune System

7. Function of the Immune System(Self/Non-self Discrimination) • To protect from pathogens • Intracellular (e.g. viruses and some bacteria and parasites) • Extracellular (e.g. most bacteria, fungi and parasites) • To eliminate modified or altered self

8. Disease = Bolus of infection x virulence immunity Infection and Immunity Balance infection immunity

9. Effects of the Immune System • Beneficial: • Protection from Invaders • Elimination of Altered Self • Detrimental: • Discomfort and collateral damage (inflammation) • Damage to self (hypersensitivity or autoimmunity)

10. Overview of the Immune System

11. Innate Host Defenses Against Infection • Anatomical barriers • Mechanical factors • Chemical factors • Biological factors • Humoral components • Complement • Coagulation system • Cytokines • Cellular components • Neutrophils • Monocytes and macrophages • NK cells • Eosinophils

12. Anatomical Barriers - Mechanical Factors

13. Anatomical Barriers - Chemical Factors

14. Anatomical Barriers - Biological Factors

15. Humoral Components

16. Cellular Components

17. PhagocytosisandIntracellular Killing

18. Phagocytes - Neutrophils (PNMs) • Characteristic nucleus, cytoplasm • Granules • CD 66 membrane marker

19. Characteristics of Neutrophil Granules primary granules secondary granules azurophilic; characteristic of young neutrophils; specific for mature neutrophils contain cationic proteins, lysozyme, defensins, elastase and myeloperoxidase contain lysozyme, NADPH oxidase components, lactoferrinand B12-binding protein

20. Phagocytes - Macrophages • Characteristic nucleus • Lysosomes • CD14 membrane marker

22. Phagocyte Response to Infection • The SOS Signals • N-formyl methionine-containing peptides • Clotting system peptides • Complement products • Cytokines released by tissue macrophages • Phagocyte response • Vascular adherence • Diapedesis • Chemotaxis • Activation • Phagocytosis and killing

23. Phagocytosis

24. Initiation of Phagocytosis Attachment via Receptors: IgG FcR Complement R ScavengerR Toll-like R

25. Determinants Recognized by the Innate Immune System PAMPs – Pathogen Associated Molecular Patterns PRRs – Pattern Recognition Receptors

29. Phagocytosis • Attachment • Pseudopod extension • Phagosome formation • Granule fusion • Phagolysosome formation

30. Summary of Intracellular Killing Pathways

31. G-6-P-dehydrogenase Glucose +NADP+ Pentose-P + NADPH NADPH oxidase Cytochrome b558 NADPH + O2 NADP++ O2- Superoxide dismutase 2O2- + 2H+ H2O2 + 1O2 2O2- + H2O2 OH* + OH- + 1O2 Toxic compounds – Superoxide anion (O2-), Hydrogen peroxide (H2O2), Singlet oxygen (1O2) and Hydroxyl radical (OH*) Respiratory Burst Oxygen-Dependent Myeloperoxidase-Independent Reactions

32. myeloperoxidase H2O2 + Cl- OCl- + H2O 1O2+Cl-+ H2O 2OCl- + H2O Toxic compounds – Hypochlorous acid (OCl-), and Singlet oxygen (1O2) Respiratory Burst Oxygen-Dependent Myeloperoxidase-Dependent Reactions

33. Respiratory Burst Detoxification Reactions Superoxide dismutase 2O2- + 2H+ H2O2+O2 Catalase 2 H2O2 H2O + O2

34. Oxygen-Independent Killing in the Phagolysosome Effector Molecule Function Cationic proteins (cathepsin) Damage to microbial membranes Lysozyme Hydrolyses mucopeptides in the cell wall Lactoferrin Deprives pathogens of iron Hydrolytic enzymes (proteases) Digests killed organisms

35. IFNγ  TNF TNF Nitric Oxide Nitric Oxide Dependent Killing

36. NK and LAK cells ADCC (K) cell Activated macrophages Eosinophils They all kill foreign and altered self targets Non-specific Killer Cells

37. also known as large granular lymphocytes (LGL) kill virus-infected or malignant cells identified by the presence of CD56 & CD16 and absence of CD3 activated by IL2 and IFN-γto become LAK cells Natural Killer (NK) cells

38. kills malignant cells kills transformed and malignant cells Lymphokine Activated Killer (LAK) cell IFN IFN IL2 IL2

39. MHC I • KIR • KAR • KAL • No Killing • Killing Regulation of NK Cell Function

40. K Cells • morphologically undefined • mediate ADCC • have Fc receptor • recognize antibody coated targets • could be NK cells (IgG), macrophages (IgG), eosinophils (IgE) or other cells (IgG)

41. Individual resistance Age Sex Stress Diet, malnutrition Intercurrent disease or trauma Therapy against other diseases

42. Inflammation • Redness • Pain • Heat • Swelling (edema) • Acute-phase proteins activated (complement, cytokine, kinins) - chemical messengers • Vasodilation (histamine, kinins, prostaglandins, leukotrienes) - bring in more help • Margination and emigration of WBCs • Tissue repair

43. Chemicals Released by Damaged Cells

44. Inflammation

45. Inflammation

46. Fever: Abnormally High Body Temperature • Hypothalamus normally set at 37°C • Gram-negative endotoxin cause phagocytes to release interleukin 1 • Hypothalamus releases prostaglandins that reset the hypothalamus to a high temperature • Body increases rate of metabolism and shivering to raise temperature • When IL-1 is eliminated, body temperature falls. (Crisis)