IMMUNITY

1. IMMUNITY DR VIDYA PAI PROF , MICROBIOLOGY, YMC

2. Specific learning Objectives • Define and classify Immunity • Describe the characteristic features of innate immunity • Enumerate and describe types of innate immunity • Enumerate and explain factors affecting innate immunity • Enumerate and explain mechanisms of innate immunity

3. Nothing in biology makes sense except in the light of evolution. - Theodosius Dobzhansky

4. DEFINITION • Mechanism of defense in the host • To resist invading micro- organisms or foreign antigens. • Immunity: Is defined as the response exhibited by the host against any foreign antigens including microorganisms. • It plays a major role for prevention of infectious diseases • Protects an individual from microorganisms and potentially harmful substances

5. Classification/ Types of Immunity Immunity INNATE/ NON SPECIFIC ADAPTIVE/ ACQUIRED/ SPECIFIC

6. Innate (Nonspecific) Immunity

7. Innate Immunity – Immunity possessed by an individual since birth due to genetic make-up (Inherited from parents). • no exposure to an antigen. • immunity is non-specific in nature • It has no immunological memory.

8. Types of innate immunity • Species • Racial • Individual

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

10. Anatomical Barriers - Mechanical Factors

11. Anatomical Barriers - Chemical Factors

12. Anatomical Barriers - Biological Factors

14. Humoral Components

15. Cellular Components

16. Phagocytosis and Intracellular Killing

17. Pattern recognition receptors/ systems • Specific receptors bind to characteristic pathogen molecules. 1. Extracellular • a. Lysozyme (mucus and tears) – against peptidoglycans • b. Psoriacin (skin) – against E. coli. Can be induced by sunlight (UVB) via vitamin D. • c. AMPS – defensive peptides that that typically kill by disrupting bacterial • membranes. • d. Mannose-binding lectin (plasma) – activates complement. • e. C-reactive protein (CRP) (plasma) also recognizes microbes and damaged selfcells. • f. Lipopolysaccharide binding protein (LBP) specifically recognizes gram negative Bacteria.

18. 2. Cytoplasmic - NOD proteins (Nucleotide-binding oligomerization domains) 3. Membrane Bound – the Toll-like receptors (TLRs)

19. Phagocytosis – Is the process by which Neutrophils and macrophages engulf and destroy foreign antigens (microorganisms). • Phagocytosis occurs in four stages;

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

21. Phagocytosis 1. Attachment - The infective agent gets attached to the membrane of the phagocyte.

22. 2. Chemotaxis - Phagocytes reach the of inflammation attracted by chemotactic substances.

23. 3. Ingestion - The foreign particle is surrounded by the cell membrane which then invaginates and produces a phagosome within the cell. The membrane of the phagosome fuses with a lysosome to form a phagolysosome.

24. 4.Intracellular Killing Pathways

25. 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

26. 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

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

28. 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

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

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

31. Natural Killer (NK) cells • 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

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

33. 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)

34. Other mechanisms • Inflammation – leads to vasodilatation and increased cellular infiltration • Fever – destroys the microorganism and induces interferons • Cytokines – IL-1. IL-6, TNF-α

35. Summary of cells • Neutrophils - the infantry in the modern sense, and the first on-site defenders. 2. Macrophages - the cavalry of the outfit. Phagocytosis causes them to secrete IL-1, IL-6 and TNFα, all inflammation activators. Always on the lookout for pathogens, and after phagocytizing, they relay info about the pathogen to the Th cells (unlike neutrophils). 3. Dendritic cells - the scouts and patrols. Most important initial trigger of the adaptive response. 4. NK Cells - function by pattern recognition making them part of innate defenses. Principally attack rogue-self by inducing apoptosis.

36. Factors affecting innate immunity • Extremes of age • Nutrition of the individual • Hormonal influences • Any other chronic disease • Medication • Genetic make up of individual

37. Learning Objectives achieved?

40. Acquired Immunity (specific) Immunity that an organism develops during lifetime. • Not genetically determined. • May be acquired naturally or artificially.

41. Mechanism of acquired immunity • Humoral ( antibody mediated) • Specific antibodies • Lysis of antigens • Removal of antigen by Phagocytosis • Cell mediated Immunity • By sensitized T lymphocytes

43. Naturally Acquired Immunity • Naturally Acquired Active Immunity: • Antigens or pathogens enter body naturally. • Body generates an immune response to antigens. • Immunity may be lifelong (chickenpox or mumps) or temporary (influenza or intestinal infections).

44. Naturally Acquired Passive Immunity: • Antibodies pass from mother to fetus via placenta or breast feeding (colostrum). • No immune response to antigens. • Immunity is usually short-lived (weeks to months). • Protection until child’s immune system develops.

45. Artificially Acquired Immunity • Artificially Acquired Active Immunity: • Antigens are introduced in vaccines (immunization). • Body generates an immune response to antigens. • Immunity can be lifelong (oral polio vaccine) or temporary (tetanus toxoid).

46. Artificially Acquired Passive Immunity • Preformed antibodies (antiserum) are introduced into body by injection. • Snake antivenom injection from horses or rabbits. • Immunity is short lived (half life three weeks). • Host immune system does not respond to antigens.

47. Differences between Innate and acquired immunity

48. Edward Jenner Discovery of small pox vaccine

49.  disease diphtheria, tetanus human, horse antibody source  indication human varicella zoster horse gas gangrene, botulism, snake bite, scorpion sting prophylaxis, therapy immunodeficiencies post-exposure post-exposure human human rabies, prophylaxis hypogamma-globulinemia Passive Immunization

50. Disadvantages Advantages Advantages and Disadvantages of Passive Immunization no long term protection serum sickness immediate protection risk of hepatitis and Aids graft vs. host disease (cell graft only)