1. INNATE ( NON-SPECIFIC ) IMMUNITY Abdul Ghaffar Microbiology and Immunology

2. macrophages, neutrophils complement, interferon, TNF etc. T cells; other effectors cells antibodies Components of the Immune System

3. Balance between Infection and Immunity infection immunity

4. Response to Infection adaptive immunity infection x disease Innate immunity no disease recovery re-infection no disease x

7. Components of Innate and Adaptive Immunity Innate Immunity Adaptive Immunity skin, gut Villi, lung cilia,etc many protein and non-protein secretions phagocytes , NK cell eosinophils, K cells physical barriers soluble factors cells none Immunoglobulins (antibody) T and B lymphocytes

8. Effector mechanisms in Innate Immunity -1 Site Component Functions Peristalsis, low pH bile salts, fatty acids columnar cells GI tract Skin squamous cells sweat desquamation flushing, fatty acids tracheal cilia Lung mucociliary elevator surfactants

9. Effector mechanisms in Innate Immunity -2 Site Component Functions Nasopharynx and eye mucus, saliva, tears flushing, lysozyme Phagocytes, K, NK & LAK cells Blood and Lymphiod organs phagocytosis and intracellular killing direct and antibody dependent cytolysis

10. Effector mechanisms in Innate Immunity -3 Site Component s Functions Serum and other serous fluids lactoferrin,transferrin iron deprivation interferons,TNF-  antiviral proteins phagocyte activation lysozyme peptidoglycan hydrolysis fibronectin complement opsonization, enhanced phagocytosis, inflammation

11. Phagocytes are the Most Important Cells Influenced by the work of Eli Metchnikoff, George Bernard Shaw wrote: “ There is at bottom only one genuine treatment for all diseases,…to stimulate the phagocytes. Drugs are a delusion. …(when) the phagocytes are stimulated; they devour the disease…”

12. All phagocytes eat, digest and extrude

13. Phagocytes: Neutrophils phagocytosis, intracellular killing, inflammation and tissue damage characteristic nucleus, cytoplasm granules and CD67 membrane marker.

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

17. Initiation of Phagocytosis Attachment via IgG FcR ScavengerR CR

18. Respiratory Burst Oxygen Dependent Myeloperoxidase Independent Reactions 2O 2 - + H 2 O 2 .OH + OH - + 1 O 2 Glucose +NADP + G-6-P-dehydrogenase Pentose-P + NADPH NADPH + O 2 Cytochrome b558 NADP + + O 2 - 2O 2 - + 2H + Superoxide dismutase H 2 O 2 + 1 O 2

19. Respiratory Burst Oxygen Dependent Myeloperoxidase dependent reactions H 2 O 2 + 1 O 2 2O 2 - + 2H + Superoxide dismutase H 2 O 2 + Cl - myeloperoxidase OCl - + H 2 O H 2 O + O 2 2 H 2 O 2 catalase OCL - + H 2 O 1 O 2 + Cl - + H 2 O

20. Pathways of Intracellular Killing

21. Mediators of Oxygen Independent Killing in the Phago-lysosome 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

22. Nitric Oxide Dependent Killing IFN  TNF TNF Nitric Oxide

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

26. Regulation of NK Cell Function