Immunology (elective) MLIM-101

1. Lecture: 1 Immunology (elective)MLIM-101 Prepared by: Dr. Mohamed S. Abdel-Latif

2. INNATE ( NON-SPECIFIC ) IMMUNITY

3. Learning Outcome: At this time you should know the following: 1. Differences between the non-specific and specific immune functions. 2. Humoral components of the non-specific immune system and their action. 3. Cellular components of the non-specific immune function and their action. 4. Pathways of intracellular killing of bacteria by phagocytes and their characteristic features. 5. Effect of humoral components such as interferon, TNF, IL-2, complement etc. on cellular components of the non-specific immune system.

4. "When the mind is ready,a teacher appears.“ Chinese Proverb

5. mφ pl neu CD8+ CTL ery nk CD4+ TH1 thy TH2 mye lym Development of the Immune System

6. Myeloid cells lymphoid cells Granulocytic Monocytic T-cells B-cells Dendritic cells? Neutrophils Macrophages Helper Cytotoxic Basophils Langerhans & Plasma Eosinophils Kupffer cells Suppressor cells Dendritic cells? Cells of the Immune System

7. Nonspecific Specific Humoral Cellular Humoral Cellular complement, interferon, TNF etc. macrophages, neutrophils antibodies T cells; other effectors cells Components of the Immune System

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

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

10. Significance of the Immune System • Beneficial: • Protection from Invaders • Elimination of Altered Self • Detrimental: • Discomfort (inflammation) • Damage to self (autoimmunity)

11. No Immunologic memory Innate Immunity Adaptive Immunity Characteristicsof Innate and Adaptive Immunity Antigen independent Antigen dependent No time lag A lag period Not antigen specific Antigen specific • Development of memory

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

13. Physical Barriers to Resistance

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

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

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

17. 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…” Influenced by the work of Eli Metchnikoff, Phagocytes are the Most Important Cells

18. Phagocytes:Macrophages • phagocytosis, intracellular and extra-cellular killing, tissue repair, antigen presentation for specific immune response • characteristic nucleus and CD14 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, proteases and myeloperoxidase contain lysozyme, NADPH oxidase, lactoferrinand B12-binding protein

20. Phagocyte Response to Infection • The SOS Signals • N-formyl methionine • Clotting system peptides • Complement products • Phagocyte response • Vascular adherence • Diapedesis • Chemotaxis • Activation • Phagocytosis and killing

21. ScavengerR IgG FcR CR Toll-like R Initiation of Phagocytosis Attachment via

22. Glucose +NADP+ G-6-P-dehydrogenase Pentose-P + NADPH NADPH + O2 Cytochrome b558 NADP++ O2- 2O2- + 2H+ Superoxide dismutase H2O2 + 1O2 2O2- + H2O2 .OH + OH- + 1O2 Respiratory Burst Oxygen Dependent Myeloperoxidase Independent Reactions

23. H2 O2 + Cl- myeloperoxidase OCl- + H2O 1O2-+Cl-+ H2O 2OCL- + H2O 2O2- + 2H+ Superoxide dismutase H2O2 + O2- 2 H2 O2 catalase H2O + O2- Respiratory Burst Oxygen Dependent Myeloperoxidase dependent reactions

24. Pathways of Intracellular Killing

25. 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

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

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

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

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

30. Regulation of NK Cell Function

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

32. Assignment: As a part of the semester activity, group of students is selected every week to prepare a short seminar about his/her point of interest in one of the lecture topics. That to be discussed and evaluated during the next lecture.