Immunology & vaccination

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Immunology & vaccination

  1. 1. IMMUNOLOGY PROF. FATIMA MayTESORO,RPH,MSPHARMDefenses of the Host
  2. 2. Nonspecific Defenses of the Host • Susceptibility Lack of resistance to a disease • Resistance Ability to ward off disease • Nonspecific resistance Defenses against any pathogen • Specific resistance Immunity, resistance to a specific pathogen • Virulence Degree of pathogenecity • Attenuation Reduction of virulence • ANTIGEN Component of foreign material w./c interacts with immune system • Epitope antigenic determinant
  3. 3. 2 IMMUNE SYSTEM RESPONSE • INNATE – non- specific; no time lag,not intrinsically affected by contact to infectious agent. • ADAPTIVE – time lags; requires highly specific recognition of antigen and immunological memory ( DIPTHERIA) – Humoral – Cell mediated
  4. 4. • HUMORAL – effector cells are B lymphocytes & antigen recognition occur through interaction with antibody • CELL MEDIATED – effector cells is T lymphocytes and antigen recognition occur through interaction with a peptide antigen w/ T receptors
  5. 5. CELL OF THE IMMUNE SYSTEM
  6. 6. Host Defenses Figure 16.1
  7. 7. • Skin • Epidermis consists of tightly packed cells with • Keratin, a protective protein Mechanical Factors
  8. 8. • Mucous membranes • Ciliary escalator: Microbes trapped in mucus are transported away from the lungs • Lacrimal apparatus: Washes eye • Saliva: Washes microbes off • Urine: Flows out • Vaginal secretions: Flow out Mechanical Factors
  9. 9. • Fungistatic fatty acid in sebum • Low pH (3-5) of skin • Lysozyme in perspiration, tears, saliva, and tissue fluids • Low pH (1.2-3.0) of gastric juice • Transferrins in blood find iron • NO inhibits ATP production Chemical Factors
  10. 10. • Microbial antagonism/competitive exclusion: Normal microbiota compete with pathogens. Normal Microbiota
  11. 11. Formed Elements In Blood Table 16.1
  12. 12. • Percentage of each type of white cell in a sample of 100 white blood cells Differential White Cell Count Neutrophils 60-70% Basophils 0.5-1% Eosinophils 2-4% Monocytes 3-8% Lymphocytes 20-25%
  13. 13. • Neutrophils: Phagocytic • Basophils: Produce histamine • Eosinophils: Toxic to parasites, some phagocytosis • Monocytes: Phagocytic as mature macrophages • Fixed macrophages in lungs, liver, bronchi • Wandering macrophages roam tissues • Lymphocytes: Involved in specific immunity White Blood Cells
  14. 14. • Phago: eat • Cyte: cell • Ingestion of microbes or particles by a cell, performed by phagocytes Phagocytosis
  15. 15. Phagocytosis Figure 16.8a
  16. 16. Microbial Evasion of Phagocytosis • Inhibit adherence: M protein, capsules Streptococcus pyogenes, S. pneumoniae • Kill phagocytes: Leukocidins Staphylococcus aureus • Lyse phagocytes: Membrane attack complex Listeriamonocytogenes • Escape phagosome Shigella • Prevent phagosome-lysosome fusion HIV • Survive in phagolysosome Coxiella burnetti
  17. 17. • Redness • Pain • Heat • Swelling (edema) • Acute-phase proteins activated (complement, cytokine, kinins) • Vasodilation (histamine, kinins, prostaglandins, leukotrienes) • Margination and emigration of WBCs • Tissue repair Inflammation
  18. 18. Chemicals Released by Damaged Cells • Histamine Vasodilation, increased permeability of blood vessels • Kinins Vasodilation, increased permeability of blood vessels • Prostaglandins Intensity histamine and kinin effect • Leukotrienes Increased permeability of blood vessels, phagocytic attachment
  19. 19. Inflammation Figure 16.9a, b
  20. 20. Inflammation Figure 16.9c, d
  21. 21. • 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) Fever: Abnormally High Body Temperature
  22. 22. • Serum proteins activated in a cascade. The Complement System Figure 16.10
  23. 23. Effects of Complement Activation • Opsonization or immune adherence: enhanced phagocytosis • Membrane attack complex: cytolysis • Attract phagocytes Figure 16.11
  24. 24. Effects of Complement Activation Figure 16.12
  25. 25. Classical Pathway Figure 16.13
  26. 26. Alternative Pathway Figure 16.14
  27. 27. Lectin Pathway Figure 16.15
  28. 28. Some bacteria evade complement • Capsules prevent C activation • Surface lipid-carbohydrates prevent MAC formation • Enzymatic digestion of C5a
  29. 29. • Alpha IFN & Beta IFN: Cause cells to produce antiviral proteins that inhibit viral replication • Gamma IFN: Causes neutrophils and macrophages to phagocytize bacteria Interferons (IFNs)
  30. 30. Interferons (IFNs) Figure 16.16 1 2 3 4 5 Viral RNA from an infecting virus enters the cell. The infecting virus replicates into new viruses. The infecting virus also induces the host cell to produce interferon on RNA (IFN-mRNA), which is translated into alpha and beta interferons. Interferons released by the virus-infected host cell bind to plasma membrane or nuclear membrane receptors on uninfected neighboring host cells, inducing them to synthesize antiviral proteins (AVPs). These include oligoadenylate synthetase, and protein kinase. New viruses released by the virus-infected host cell infect neighboring host cells. 6 AVPs degrade viral m-RNA and inhibit protein synthesis and thus interfere with viral replication.
  31. 31. • Innate (nonspecific) Defenses against any pathogen • Immunity Specific antibody and lymphocyte response to an antigen • Antigen (Ag) A substances that causes the body to produce specific antibodies or sensitized T cells • Antibody (Ab) Proteins made in response to an antigen
  32. 32. Terminology • Serology Study of reactions between antibodies and antigens • Antiserum Generic term for serum because it contains Ab • Globulins Serum proteins • Gamma (γ) globulin Serum fraction containing Ab
  33. 33. Serum Proteins Figure 17.2
  34. 34. The Immune Response • Acquired immunity Developed during an individual's lifetime • Humoral immunity Involves Ab produced by B cells • Cell-mediated immunity Involves T cells
  35. 35. Acquired Immunity • Naturally acquired active immunity – Resulting from infection • Naturally acquired passive immunity – Transplacental or via colostrum • Artificially acquired active immunity – Injection of Ag (vaccination) • Artificially acquired passive immunity – Injection of Ab
  36. 36. Antigenic Determinants• Antibodies recognize and react with antigenic determinants or epitopes. Figure 17.3
  37. 37. Haptens Figure 17.4
  38. 38. Antibody Structure Figure 17.5a-c
  39. 39. • Monomer • 80% of serum antibodies • Fix complement • In blood, lymph, intestine • Cross placenta • Enhance phagocytosis; neutralize toxins & viruses; protects fetus & newborn • Half-life = 23 days IgG antibodies
  40. 40. • Pentamer • 5-10% of serum antibodies • Fix complement • In blood, lymph, on B cells • Agglutinates microbes; first Ab produced in response to infection IgM antibodies
  41. 41. • Dimer • 10-15% of serum antibodies • In secretions • Mucosal protection • Half-life = 6 days IgA antibodies
  42. 42. • Monomer • 0.2% of serum antibodies • In blood, lymph, on B cells • On B cells, initiate immune response • Half-life = 3 days IgD antibodies
  43. 43. • Monomer • 0.002% of serum antibodies • On mast cells and basophils, in blood • Allergic reactions; lysis of parasitic worms • Half-life = 2 days IgE antibodies
  44. 44. • Bone marrow gives rise to B cells. • Mature B cells migrate to lymphoid organs. • A mature B cells recognizes epitopes. Clonal Selection
  45. 45. Clonal Selection Figure 17.8
  46. 46. Self-tolerance • Body doesn't make Ab against self • Clonal deletion – The process of destroying B and T cells that react to self antigens
  47. 47. The Results of Ag-Ab Binding Figure 17.9
  48. 48. Antibody titer:• Is the amount of Ab in serum Figure 17.10
  49. 49. Monoclonal Antibodies • Hybridomas are produced by fusing a cancer cell with an Ab-secreting plasma cells • The hybridoma cell culture is immortal and produces monoclonal Abs (Mabs) • Immunotoxins: Mabs conjugated with a toxin to target cancer cells • Chimeric Mabs: Genetically modified mice that produce Ab with a human constant region • Humanized Mabs: Mabs that are mostly human, except for mouse antigen-binding
  50. 50. Monoclonal Antibodies Figure 17.11
  51. 51. • Interleukin-1 Stimulates TH cells • Interleukin-2 Activates TH, B, TC, and NK cells • Interleukin-12 Differentiation of CD4 cells • γ-Interferon Increase activity of macrophages • Chemokines Cause leukocytes to move to an infection Immune system cells communicate via cytokines
  52. 52. • Specialized lymphocytes, mostly T cells, respond to intracellular Ags • After differentiating in the thymus, T cells migrate to lymphoid tissue • T cells differentiate into effector T cells when stimulated by an Ag • Some effector T cells become memory cells Cell-Mediated Immunity
  53. 53. • M (microfold) cells in • Peyer's patches which contains • Dendritic cells which are antigen-presenting cells and • T cells Pathogens entering the gastrointestinal or respiratory tracts pass through:
  54. 54. Dendritic cells present antigens Figure 17.12
  55. 55. • Helper T Cells (CD4, TH) – TH1 Activate cells related to cell-mediated immunity – TH2 Activate B cells to produce eosinophils, IgM, and IgE • Cytotoxic T Cells (CD8, TC) – Destroy target cells with perforin T Cells
  56. 56. • Delayed Hypersensitivity T Cells (TD) – Associated with allergic reaction, transplant rejection, and tuberculin skin test • Suppressor T cells (TS) – Turn off immune response when Ag no longer present T Cells
  57. 57. Helper T Cells Figure 17.13
  58. 58. Cell-mediated Cytotoxicity Figure 17.14
  59. 59. Nonspecific Cells • Activated macrophages: Macrophages stimulated by ingesting Ag or by cytokines • Natural killer cells: Lymphocytes that destroy virus- infected cells, tumor Figure 17.15
  60. 60. T-independent Antigens Figure 17.17 B cell
  61. 61. T-independent Antigens Figure 17.16
  62. 62. Antibody-Dependent Cell-Mediated Cytotoxicity Figure 17.18
  63. 63. Vaccine History • Variolation: Inoculation of smallpox into skin (18th century) • Vaccination: Inoculation of cowpox into skin • Herd immunity results when most of a population is immune to a disease.
  64. 64. • DtaP – Diphtheria: Purified diphtheria toxoid – Pertussis: Acellular fragments of B. pertussis – Tetanus: Purified tetanus toxoid • Meningococcal meningitis: Purified polysaccharide from N. meningitidis • Haemophilus influenzae type b meningitis: Polysaccharides conjugated with protein • Pneumococcal conjugate vaccine: S. pneumoniae antigens conjugated with protein Principal Vaccines
  65. 65. • Smallpox: Live vaccinia virus • Poliomyelitis: Inactivated virus • Rabies: Inactivated virus • Hepatitis A: Inactivated virus • Influenza: Inactivated or attenuated virus • Measles: Attenuated virus • Mumps: Attenuated virus • Rubella: Attenuated virus • Chickenpox: Attenuated virus • Hepatitis B: Antigenic fragments (recombinant vaccine) Principal Vaccines Used in the United States to Prevent Viral Diseases in Humans
  66. 66. Precipitation Reactions • Involve soluble antigens with antibodies Figure 18.3
  67. 67. Agglutination Reactions • Involve particulate antigens and antibodies • Antigens may be: • On a cell (direct agglutination) • Attached to latex spheres (indirect or passive agglutination) Figure 18.4
  68. 68. Antibody Titer • Is the concentration of antibodies against a particular antigen Figure 18.5
  69. 69. Hemagglutination • Hemagglutination involves agglutination of RBCs. • Viral hemagglutination inhibition tests for antibodies by the antibodies' ability to prevent viruses from agglutinating RBCs. Figure 18.7
  70. 70. Neutralization Reactions • Eliminate the harmful effect of a virus or exotoxin Figure 18.8b
  71. 71. Complement Fixation Figure 18.9.1
  72. 72. Complement Fixation Figure 18.9.2
  73. 73. Fluorescent Antibody Techniques (Direct) Figure 18.10a
  74. 74. Fluorescent Antibody Techniques (Indirect) Figure 18.10b
  75. 75. Enzyme-Linked Immunosorbent Assay (Direct ELISA) Figure 18.12a
  76. 76. Enzyme-Linked Immunosorbent Assay (Indirect ELISA) Figure 18.12b
  77. 77. Serological Tests Figure 18.13
  78. 78. Serological Tests • Direct tests detect antigens (from patient sample) • Indirect tests detect antibodies (in patient's serum)
  79. 79. Serological Tests • Agglutination: Particulate antigens • Hemagglutination: Agglutination of RBCs • Precipitation: Soluble antigens • Fluorescent-antibody technique: Antibodies linked to fluorescent dye • Complement fixation: RBCs are indicator • Neutralization: Inactivates toxin or virus • ELISA: Peroxidase enzyme is the indicator

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