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2. Overview of the Immune System Interactions between the two systems Immune System Innate (Nonspecific) 1 oline of defense Adaptive (Specific) 2 oline of defense Protects/re-exposure Cellular Components Humoral Components Cellular Components Humoral Components 3. Comparison of Innate and Adaptive Immunity
Innate Immunity Adaptive Immunity 4. Cells of the Immune System Immune System Myeloid Cells Lymphoid Cells Granulocytic Monocytic T cells B cells Neutrophils Basophils Eosinophils Macrophages Kupffer cells Dendritic cells Helper cells Suppressor cells Cytotoxic cells Plasma cells NK cells 5. Development of the Immune System ery pl mye neu m lym nk thy CD8 + CD4 + CTL TH2 TH1 6. Function of the Immune System (Self/Non-self Discrimination)
7. Infection and Immunity Balance infection immunity Bolus of infection x virulence immunity Disease = 8. Effects of the Immune System
9. Innate (Nonspecific) Immunity 10. Overview of the Immune System Immune System Innate (Nonspecific) Adaptive (Specific) Cellular Components Humoral Components Cellular Components Humoral Components 11. Innate Host Defenses Against Infection
12. Anatomical Barriers - Mechanical Factors System or Organ Cell type Mechanism Skin Squamous epithelium Physical barrier Desquamation Mucous Membranes Non-ciliated epithelium ( e.g.GI tract) Peristalsis Ciliated epithelium ( e.g.respiratory tract) Mucociliary elevator Epithelium ( e.g.nasopharynx) Flushing action of tears, saliva, mucus, urine 13. Anatomical Barriers - Chemical Factors System or Organ Component Mechanism Skin Sweat Anti-microbial fatty acids Mucous Membranes HCl (parietal cells) Tears and saliva Low pH Lysozyme and phospholipase A Defensins (respiratory & GI tract) Antimicrobial Sufactants (lung) Opsonin 14. Anatomical Barriers - Biological Factors System or Organ Component Mechanism Skin and mucous membranes Normal flora Antimicrobial substances Competition for nutrients and colonization 15. Humoral Components Component Mechanism Complement Lysis of bacteria and some viruses Opsonin Increase in vascular permeability Recruitment and activation of phagocytic cells Coagulation system Increase vascular permeability Recruitment of phagocytic cells -lysin from platelets a cationic detergent Lactoferrin and transferrin Compete with bacteria for iron Lysozyme Breaks down bacterial cell walls Cytokines Various effects 16. Cellular Components Cell Functions Neutrophils Phagocytosis and intracellular killing Inflammation and tissue damage Macrophages Phagocytosis and intracellular killing Extracellular killing of infected or altered self targets Tissue repair Antigen presentation for specific immune response NK and LAK cells Killing of virus-infected and altered self targets Eosinophils Killing of certain parasites 17. Phagocytosis and Intracellular Killing 18. Phagocytes - Neutrophils (PNMs)
19. Characteristics of Neutrophil Granules primary granules containcationic proteins, lysozyme, defensins, elastase andmyeloperoxidase secondary granules contain lysozyme, NADPH oxidase components,lactoferrin and B12-binding protein azurophilic; characteristic of young neutrophils; specific for mature neutrophils 20.
Phagocytes - Macrophages 21. Phagocyte Response to Infection
22. Attachment via Receptors: IgG FcR ScavengerR Complement R Toll-like R Initiation of Phagocytosis 23. Phagocytosis
24. Respiratory Burst Oxygen-Dependent Myeloperoxidase-Independent Reactions Toxic compounds Superoxide anion (O 2 - ), Hydrogen peroxide (H 2 O 2 ), Singlet oxygen ( 1 O 2 ) and Hydroxyl radical (OH*) Pentose-P + NADPH G-6-P-dehydrogenase Glucose +NADP + NADPH oxidase Cytochromeb558 NADP + +O 2 - NADPH + O 2 Superoxide dismutase H 2 O 2+1 O 2 2O 2 -+ 2H + 2O 2 -+ H 2 O 2 OH*+ OH -+1 O 2 25. Respiratory Burst Oxygen-Dependent Myeloperoxidase-Dependent Reactions myeloperoxidase OCl - + H 2 O H 2 O 2+Cl - 2OCl -+ H 2 O 1 O 2 + Cl - + H 2 O Toxic compounds Hypochlorous acid (OCl - ), and Singlet oxygen ( 1 O 2 ) 26. Respiratory Burst Detoxification Reactions H 2 O 2 + O 2 Superoxide dismutase H 2 O+ O 2 Catalase 2O 2 -+ 2H + 2 H 2 O 2 27. 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 28. Summary of Intracellular Killing Pathways Intracellular Killing Oxygen Dependent Oxygen Independent Myleoperoxidase Dependent Myleoperoxidase Independent 29. Nitric Oxide Dependent Killing IFN TNF TNF Nitric Oxide Nitric Oxide 30. Non-specific Killer Cells
31. Natural Killer (NK) cells
32. Lymphokine Activated Killer (LAK) cell IL2 IFN IFN IL2 kills malignant cells kills transformed and malignant cells 33. Regulation of NK Cell Function
34. K Cells