VACCINES                       REFERENCES: a) Abbas; b) Kuby; and c) Lectures of Dr Nina Gloriani, MD, PhDMonday, Septembe...
EDWARD JENNER       • Father of Vaccinology &              Founder of Immunology       • Major contribution: first         ...
LOOKING BACK...      •      18th century: Small pox      •      19th century: Rabies; typhoid; cholera; plague      •     ...
RECALL:                             IMMUNITYMonday, September 10, 2012
ACQUIRING PASSIVE AND                     ACTIVE IMMUNITYMonday, September 10, 2012
ACTIVE & PASSIVE                          IMMUNITYMonday, September 10, 2012
PASSIVE                     IMMUNIZATION      • Administration of preformed             antibodies to treat infection     ...
PASSIVE                     IMMUNIZATION      • Preformed antibodies generally made in             horses, but occasionall...
Monday, September 10, 2012
COMMONLY                             USED AGENTS                             DISEASE               AGENT     Black widow s...
PASSIVE                     IMMUNIZATIONMonday, September 10, 2012
NON-SPECIFIC IMMUNOTHERAPY • Same compounds that act as adjuvants for vaccines also   used on their own to boost the gener...
IMMUNOTHERAPY              OF TUMORSMonday, September 10, 2012
Monday, September 10, 2012
Monday, September 10, 2012
ACTIVE                             IMMUNITY      •      The process of administering antigen to a live host to            ...
GENERAL TYPE OF                                VACCINESMonday, September 10, 2012
ANTIGENIC PREPARATIONS             USED AS VACCINESMonday, September 10, 2012
COMPARING                               NOTESMonday, September 10, 2012
LIVE ATTENUATED VACCINESMonday, September 10, 2012
EFFECT OF VACCINES   ON VIRAL DISEASESMonday, September 10, 2012
KILLED-WHOLE    ORGANISM VACCINEMonday, September 10, 2012
POLIO: LIVE VERSUS KILLED                              VACCINEMonday, September 10, 2012
Monday, September 10, 2012
SUBCELLULAR       FRAGMENTS VACCINESMonday, September 10, 2012
Monday, September 10, 2012
TOXIN-BASED                               VACCINESMonday, September 10, 2012
Monday, September 10, 2012
DNA VACCINESMonday, September 10, 2012
THE MALARIA VACCINE                         STRATEGYMonday, September 10, 2012
VACCINES IN                             GENERAL USEMonday, September 10, 2012
VACCINES RESTRICTED TO                         CERTAIN GROUPSMonday, September 10, 2012
SAFETY CONCERNS WITH                      VACCINESMonday, September 10, 2012
WANTED VACCINES...Monday, September 10, 2012
ADJUVANTSMonday, September 10, 2012
EFFECTS OF ADJUVANTS       • Concentration of antigen in a site where              lymphocytes are exposed to it          ...
START HEREMonday, September 10, 2012
VACCINE               CONSIDERATIONS #1      • Type      • Indications      • Target group      • Dose      • Route of Adm...
TARGET GROUPSMonday, September 10, 2012
Monday, September 10, 2012
MONITORING        •      Side effects: Fever                   •         LOCAL SYMPTOMS AT                             INJ...
VACCINE               CONSIDERATIONS #2      • SAFETY: Toxicity, teratogenicity, pyrogenicity,             adverse reactio...
SAFETY: ADVERSE                          REACTIONS      • MILD: adverse reaction does not interfere with              norm...
EFFICACY      • Streptococcus pneumoniae; Neisseria meningitidis;             Hemophilus influenzae capsular polysaccharide...
VACCINE-                             PREVENTABLE                               DISEASESMonday, September 10, 2012
VACCINES FOR                                 YOU                                  Following primary series of             ...
VACCINES FOR                                 YOU                                  Following primary series of             ...
VACCINES FOR                                 YOU                                                    Following primary seri...
VACCINES FOR                                 YOU                                  • RUBELLA                               ...
VACCINES FOR                                 YOU                                  • RUBELLA                               ...
VACCINES FOR                                 YOU                                                    • RUBELLA             ...
VACCINES FOR                                 YOU                                  • MMR                                  •...
VACCINES FOR                                 YOU                                  • MMR                                  •...
VACCINES FOR                                 YOU                                                    • MMR                 ...
VACCINES          FOR YOU                             • CHICKEN POX (VARICELLA)                             • Live attenua...
VACCINES          FOR YOU                             • CHICKEN POX (VARICELLA)                             • Live attenua...
VACCINES          FOR YOU                                                • CHICKEN POX (VARICELLA)                        ...
VACCINES          FOR YOU                             • HEPATITIS A                             • Inactivated hepatitis A ...
VACCINES          FOR YOU                             • HEPATITIS A                             • Inactivated hepatitis A ...
VACCINES          FOR YOU                                                • HEPATITIS A                                 Add...
VACCINES          FOR YOU                             • INFLUENZA                             • Highly purified surface ant...
VACCINES          FOR YOU                             • INFLUENZA                             • Highly purified surface ant...
VACCINES          FOR YOU                                                • INFLUENZA                                 Addit...
VACCINES  FOR YOU                    • CHOLERA                             • Orochol E Berna contains not < 2x109         ...
VACCINES  FOR YOU                    • CHOLERA                             • Orochol E Berna contains not < 2x109         ...
VACCINES  FOR YOU                                       • CHOLERA                                                • Orochol...
VACCINES  FOR YOU                             • TYPHOID                             • Vi capsular polysaccharide          ...
VACCINES  FOR YOU                             • TYPHOID                             • Vi capsular polysaccharide          ...
VACCINES  FOR YOU                                                • TYPHOID                                 Additional     ...
VACCINES  FOR YOU                    • PNEUMOCOCCUS                             • Purified polysaccharide of               ...
VACCINES  FOR YOU                    • PNEUMOCOCCUS                             • Purified polysaccharide of               ...
VACCINES  FOR YOU                                       • PNEUMOCOCCUS                                                • Pu...
VACCINES  FOR YOU                             • PNEUMOCOCCUS                             • Dosage: Initial Injections: Sin...
VACCINES  FOR YOU                             • PNEUMOCOCCUS                             • Dosage: Initial Injections: Sin...
VACCINES  FOR YOU                                                • PNEUMOCOCCUS                                           ...
ISSUES TO                             CONSIDER       •      Which vaccine to administer to whom?       •      When to vacc...
EXPANDED                      IMMUNIZATION                        PROGRAMSMonday, September 10, 2012
The 7 EPI Diseases  Measles                   Diphtheria  Poliomyelitis             Hepatitis   B  Pertussis  Tetanu...
1976 Official launching of EPI in the Philippines  1977 BCG & DPT2 for infants in priority areas       BCG & DPT2 expanded...
1986 Universal Child Immunization Goal by 1990-UN       Start of Rotary International mass campaigns –Polio  1987       Pl...
Bacteria                   Disease          Antigen           Efficacy  Streptococcus                               Capsul...
Vaccine            Reason for Immunization                             Given at the earliest possible age protects        ...
Diseases to be immunized                      Age                                      against                     Birth  ...
Tetanus toxoid Immunization Schedule for                     Women                                                        ...
Philippine Immunization                            Flagship Programs    Poliomyelitis Eradication    Measles Elimination...
TAKE-HOME                                QUIZ      • Next to Smallpox, why do you think that polio             and measles...
IMMUNOLOGIC TOLERANCE    AND AUTOIMMUNITYMonday, September 10, 2012
RECALL...      • Immunologic tolerance: unresponsiveness              to self-antigens      • WHAT WE WILL LEARN:       • ...
ON ENCOUNTER WITH          LYMPHOCYTES...Monday, September 10, 2012
ON ENCOUNTER WITH          LYMPHOCYTES... The choice among lymphocyte activation, tolerance, and ignorance is determined b...
IMPORTANCE OF IMMUNOLOGIC         TOLERANCE      •       the knowledge that self-antigens normally induce tolerance      •...
CENTRAL &                             PERIPHERAL   •      central tolerance:          induced when developing          lym...
AUTOIMMUNITY      • Principal factors in the             development of             autoimmunity:      •      inheritance ...
CENTRAL T-LYMPHOCYTE               TOLERANCE                                                              • Negative      ...
PERIPHERAL T-         LYMPHOCYTES & ANERGY      • Peripheral tolerance:      • induced when mature T cells recognize self ...
ANERGY      •       ANERGY: functional inactivation of T-lymphocytes that occurs              when these ceIls recognize a...
ACTIVATION-INDUCED CELL                       DEATH : DELETIONMonday, September 10, 2012
IMMUNE SUPPRESSIONMonday, September 10, 2012
Characteristics of self and foreign (e.g. microbial)         protein antigens that determine why the self       antigens i...
CENTRAL TOLERANCE IN          B-CELLSMonday, September 10, 2012
PERIPHERAL                 TOLERANCE IN B-CELLSMonday, September 10, 2012
AUTOIMMUNE DISEASES                   & MHC MOLECULESMonday, September 10, 2012
Monday, September 10, 2012
MOLECULAR MIMICRY &                      AUTOIMMUNITYMonday, September 10, 2012
SUMMARY      •       Immunologic tolerance: specific              unresponsiveness to an antigen induced by exposure of    ...
SUMMARY       •      Autoimmune diseases: result from a failure of self-              tolerance       •      Multiple fact...
SUMMARY      •       Central tolerance: induced by the death of immature              lymphocytes that encounter antigens ...
SUMMARY      • T-CELLS:      • Peripheral tolerance: induced by multiple mechanisms        • Anergy (functional inactivati...
SUMMARY      •B-CELLS      • central tolerance: induced when              immature cells recognize self antigens in the   ...
SUMMARY      • AUTOIMMUNITY      • Many genes contribute to the development of              autoimmunity      • The strong...
vanderbilt.edu     IMMUNE RESPONSE AGAINST       TUMORS/TRANSPLANTS                                              Reference...
CALENDAR FOR BIO 151                       DATE                           ACTIVITY  September 11                TUMORS, TR...
WHAT ARE TUMORS?                 webmd.com   •      Simply means a mass of          cells   •      Can be either benign or...
IMMUNE RESPONSE TO                                  TUMORS    •       T cells generally mount            effective surveil...
IMMUNE RESPONSE TO                                  TUMORS    •       NK cells play a role in            containing tumor ...
WHAT IS CANCER?     •       diseases in which there is loss             of regulation of the             proliferative pro...
CANCER      •      Control is important to             ensure that cells only             divide when needed             (...
DEFENSE AGAINST                 UNCONTROLLED PROLIFERATION     • A cell can initiate cell            death (suicide) when ...
WHAT ARE ORGANS                          TRANSPLANTS?     •       surgical operation in             which a failing or dam...
WHAT ARE ORGANS                          TRANSPLANTS?   •      Cadaveric organ donation involves          removing organs ...
SO WHAT’S IT FOR                              IMMUNOLOGY?      • CANCER: enhancing immunity against             the tumors...
WHAT WE WILL LEARN...      • What are the antigens in tumors and tissue              transplants that are recognized as fo...
IMMUNE SURVEILLANCE                      • 1950s: a physiologic function of the                             adaptive immun...
EVIDENCES SUPPORTING                    THE CONCEPT OF                 IMMUNO SURVEILLANCEMonday, September 10, 2012
TUMOR ANTIGENS                               • Malignant                                 tumors                           ...
IMMUNE MECHANISM FOR                       TUMOR REJECTION        • The principal immune mechanism of tumor               ...
IMMUNE MECHANISM FOR                       TUMOR REJECTION        • CTLs responses against tumor cells are often induced  ...
IMMUNE MECHANISM FOR                       TUMOR REJECTION     • anti-tumor CD4+ T-            cell responses and         ...
EVASION OF    IMMUNE RESPONSE       BY TUMORS       •      Immune response often fail to              check tumor growth b...
EVASION OF IMMUNE                   RESPONSE BY TUMORS       • Growing tumors also develop mechanisms for              eva...
IMMUNOTHERAPY                           FOR TUMORS                   • MAIN GOAL:                      • provide antitumor...
IMMUNOTHERAPY                 VS CHEMOTHERAPY      • Chemotherapy/             Irradiation: may have             devastati...
STRATEGY 1:                   PASSIVE IMMUNITY       • immune effectors are injected into cancer              patients    ...
EXAMPLE: BREAST CANCER                   IMMUNOTHERAPY       •      ALL information from: Critical Reviews in Oncology and...
Signal transduction pathways instigated                             by HER2, co-receptors and EGF-like                    ...
Clinically approved and experimental   therapeutic strategies targeting ErbB-2/   HER2 in carcinomas:   a. Trastuzumab: hu...
STRATEGIES FOR                 ENHANCING ANTITUMOR                   IMMUNE RESPONSE       •      1. Tumor-              a...
STRATEGIES FOR                 ENHANCING ANTITUMOR                   IMMUNE RESPONSE      •      2. DNA or             tra...
STRATEGIES FOR                 ENHANCING ANTITUMOR                   IMMUNE RESPONSE      • 3. tumor cell             expr...
IMMUNE RESPONSE                AGAINST TRANSPLANTSMonday, September 10, 2012
IMMUNE RESPONSE                AGAINST TRANSPLANTS         •       transplants exchanged               wenliang.myweb.uga....
IMMUNE RESPONSE                AGAINST TRANSPLANTS      • Allogeneic (allografts) and              Xenogeneic (xenografts)...
Transplantation                                Antigens                             • The antigens of                     ...
INDUCTION OF IMMUNE                               RESPONSES AGAINST                                  TRANSPLANTS          ...
INDUCTION OF IMMUNE                               RESPONSES AGAINST                                  TRANSPLANTS          ...
INDUCTION OF IMMUNE                               RESPONSES AGAINST                                  TRANSPLANTS          ...
MIXED LYMPHOCYTE                 REACTION (MLR)                             wenliang.myweb.uga.edu                        ...
MIXED LYMPHOCYTE                 REACTION (MLR)        • T-cells from one individual are cultured with               leuko...
IMMUNE MECHANISM OF                     GRAFT REJECTION     •       occurs within minutes of transplantation; characterize...
IMMUNE MECHANISM OF                     GRAFT REJECTION                                                         not common...
IMMUNE MECHANISM OF                     GRAFT REJECTION     •      occurs within days or weeks after transplantation     •...
IMMUNE MECHANISM OF                     GRAFT REJECTION                                                             antibo...
IMMUNE MECHANISM OF                     GRAFT REJECTION    •      occurs over months or years that leads to progressive lo...
PREVENTION & TREATMENT                      OF GRAFT REJECTION                                     e-steroid.comMonday, Se...
BONE MARROW                      TRANSPLANTS     •      elicit strong rejection            reactions: must perform cross- ...
QUESTIONS?Monday, September 10, 2012
elitechgroup.com                             SERODIAGNOSIS                                          Reference; Jawetz Medi...
ehrs.upenn.edu                BIOSAFETY                             2008.igem.org                                         ...
OVERVIEW OF                             DIAGNOSTICS      • 3 CATEGORIES:         • Direct: clinical specimen is examined d...
ANTIGEN DETECTION:                       DIRECT                                                            •   Application...
ANTIGEN DETECTION:                       DIRECT                                                  geneaid.com              ...
ANTIGEN DETECTION:                        INDIRECTMonday, September 10, 2012
ANTIGEN DETECTION:                    INDIRECT (enhanced)Monday, September 10, 2012
ANTIBODY DETECTION:                    SEROLOGY  http://virology-online.com                                 usada.orgMonda...
COMMON TESTS       • Classical Techniques:         • Newer Techniques:       • Complement fixation tests      • Radioimmuno...
DIAGNOSING A PRIMARY                    (ACUTE) INFECTION      • A significant rise in titre of IgG/total              anti...
DIAGNOSING A PRIMARY                    (ACUTE) INFECTION      • Presence of IgM      • EIA, RIA, and IF may be used (rapi...
DIAGNOSING A PRIMARY                    (ACUTE) INFECTION       • Seroconversion       • changing from a previously antibo...
DIAGNOSING A PRIMARY                    (ACUTE) INFECTION      • A single high titre of IgG (or total              antibod...
DIAGNOSING A RE-                INFECTION / RE-ACTIVATION      •       It is often very difficult to differentiate re-infec...
USE DEPENDS ON                  PATHOGEN       •      onset of clinical symptoms coincide with the              developmen...
READING ASSIGNMENT:                             Q: WHAT DO YOU THINK                             ARE SOME PROBLEMS        ...
medicineworld.org                                              THE SEROLOGICAL           immunology.utoronto.ca           ...
COMPLEMENT                       FIXATION TEST                                    http://virology-online.com              ...
HEMAGGLUTINATION/                    HEMAGGLUTINATION INHIBITION                            TESTS (HAI)                   ...
HEMAGGLUTINATION/                    HEMAGGLUTINATION INHIBITION                            TESTS (HAI)                   ...
IMMUNOFLUORESCENCE                    TECHNIQUE (IF)        • DIRECT: known labeled antibody interacts               with ...
IMMUNOFLUORESCENCE                    TECHNIQUE (IF)                             Respiratory Syncytial Virus (RSV)        ...
NEUTRALIZATION                             TESTS     •      potential of the serum of            neutralizing the biologic...
NEUTRALIZATION                             TESTS                                            Positive MDCC-MSB1 infected ce...
SINGLE RADIAL                         HEMOLYSIS     •       E.g. Rubella antibody.     •       LEFT PLATE: Control Plate  ...
RADIOIMMUNOASSAY                         (RIA)       • used to quantitate antigens or haptens taht can              be rad...
RADIOIMMUNOASSAY                         (RIA)       • concentration of the unlabeled (unknown)              antigen or ha...
users.rcn.comMonday, September 10, 2012
RADIOALLERGOSORBENT                       ASSAY (RAST)  lookfordiagnosis.com                              pennstatehershey...
ENZYME                  IMMUNOASSAY (EIA)       • depends on the conjugation of an enzyme to either              an antige...
ELISA    technologyinscience.blogspot.com                                           •   can detect the                    ...
ELISA      • one of the components of the conjugate             (antibody or antigen) is attached to the plate, so        ...
ELISA: ANTIGEN                       DETECTION      •      Sandwich ELISA      •      plates are usually coated with an   ...
ELISA: ANTIBODY                  DETECTION      •      INDIRECT ELISA: coating of             the ELISA plate with the ant...
ELISA: ANTIBODY                  DETECTION      •      COMPETITIVE ELISA: have an             antibody (monoclonal of poly...
ELISA & HIV                             virology-online.com                                                   hivinfosourc...
DENGUE                             SEROLOGYMonday, September 10, 2012
QUESTIONS?Monday, September 10, 2012
END OF EXAM 2                               COVERAGEMonday, September 10, 2012
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Bio 151 lectures for examination 2

  1. 1. VACCINES REFERENCES: a) Abbas; b) Kuby; and c) Lectures of Dr Nina Gloriani, MD, PhDMonday, September 10, 2012
  2. 2. EDWARD JENNER • Father of Vaccinology & Founder of Immunology • Major contribution: first reliable method of conferring lasting immunity to a major contagious disease (smallpox) • Initiated the technique of vaccinationMonday, September 10, 2012
  3. 3. LOOKING BACK... • 18th century: Small pox • 19th century: Rabies; typhoid; cholera; plague • Early 20th century: BCG;Yellow fever; pertussis: influenza; diphtheria; tetanus • After world war II: • OPV; MMR; Adenovirus; Salmonella Ty21a; varicella; Injected Polio; Rabies; Japanese encephalitis; Hepatitis A; Pneumococcus; meningococcus, Hemophilus influenza PRP, Hepatitis B; Acellular pertussisMonday, September 10, 2012
  4. 4. RECALL: IMMUNITYMonday, September 10, 2012
  5. 5. ACQUIRING PASSIVE AND ACTIVE IMMUNITYMonday, September 10, 2012
  6. 6. ACTIVE & PASSIVE IMMUNITYMonday, September 10, 2012
  7. 7. PASSIVE IMMUNIZATION • Administration of preformed antibodies to treat infection • Can be life-saving where toxins are already circulating : tetanus, diphtheria, snake bite • Important where high titer specific antibody is requiredMonday, September 10, 2012
  8. 8. PASSIVE IMMUNIZATION • Preformed antibodies generally made in horses, but occasionally obtained from recovered patients • Over 1000 donors used for each pool of ISG, and sera are screened for HIV and hepatitis B and CMonday, September 10, 2012
  9. 9. Monday, September 10, 2012
  10. 10. COMMONLY USED AGENTS DISEASE AGENT Black widow spider bite Horse antitoxin Botulism Horse antitoxin Diphtheria Horse antitoxin Hepatitis A & B Pooled human IgG Measles Pooled human IgG Rabies Pooled human IgG Snake bite Horse antivenin Tetanus Pooled human IgG or horse antitoxinMonday, September 10, 2012
  11. 11. PASSIVE IMMUNIZATIONMonday, September 10, 2012
  12. 12. NON-SPECIFIC IMMUNOTHERAPY • Same compounds that act as adjuvants for vaccines also used on their own to boost the general level of immune activityMonday, September 10, 2012
  13. 13. IMMUNOTHERAPY OF TUMORSMonday, September 10, 2012
  14. 14. Monday, September 10, 2012
  15. 15. Monday, September 10, 2012
  16. 16. ACTIVE IMMUNITY • The process of administering antigen to a live host to induce an immune response for either academic or public health reasons • Vaccines have been developed as a prophylactic measure to prevent disease caused by infectious agents, provided their use caused only low levels of morbidity • WORLD HEALTH ORGANIZATION: Expanded Program on Immunization (EPI) and Vaccine development programs/initiativesMonday, September 10, 2012
  17. 17. GENERAL TYPE OF VACCINESMonday, September 10, 2012
  18. 18. ANTIGENIC PREPARATIONS USED AS VACCINESMonday, September 10, 2012
  19. 19. COMPARING NOTESMonday, September 10, 2012
  20. 20. LIVE ATTENUATED VACCINESMonday, September 10, 2012
  21. 21. EFFECT OF VACCINES ON VIRAL DISEASESMonday, September 10, 2012
  22. 22. KILLED-WHOLE ORGANISM VACCINEMonday, September 10, 2012
  23. 23. POLIO: LIVE VERSUS KILLED VACCINEMonday, September 10, 2012
  24. 24. Monday, September 10, 2012
  25. 25. SUBCELLULAR FRAGMENTS VACCINESMonday, September 10, 2012
  26. 26. Monday, September 10, 2012
  27. 27. TOXIN-BASED VACCINESMonday, September 10, 2012
  28. 28. Monday, September 10, 2012
  29. 29. DNA VACCINESMonday, September 10, 2012
  30. 30. THE MALARIA VACCINE STRATEGYMonday, September 10, 2012
  31. 31. VACCINES IN GENERAL USEMonday, September 10, 2012
  32. 32. VACCINES RESTRICTED TO CERTAIN GROUPSMonday, September 10, 2012
  33. 33. SAFETY CONCERNS WITH VACCINESMonday, September 10, 2012
  34. 34. WANTED VACCINES...Monday, September 10, 2012
  35. 35. ADJUVANTSMonday, September 10, 2012
  36. 36. EFFECTS OF ADJUVANTS • Concentration of antigen in a site where lymphocytes are exposed to it • the “DEPOT” effect • Induction of cytokines which regulate lymphocyte function • cytokines themselves shown to be effective adjuvants, particularly when coupled directly to antigenMonday, September 10, 2012
  37. 37. START HEREMonday, September 10, 2012
  38. 38. VACCINE CONSIDERATIONS #1 • Type • Indications • Target group • Dose • Route of Administration • Monitoring Side EffectsMonday, September 10, 2012
  39. 39. TARGET GROUPSMonday, September 10, 2012
  40. 40. Monday, September 10, 2012
  41. 41. MONITORING • Side effects: Fever • LOCAL SYMPTOMS AT INJECTION SITE: Soreness, redness, swelling size • GENERAL symptoms– headache, malaise, loss of appetite, nausea, vomiting • Adverse Reactions • ContraindicationsMonday, September 10, 2012
  42. 42. VACCINE CONSIDERATIONS #2 • SAFETY: Toxicity, teratogenicity, pyrogenicity, adverse reactions • IMMUNOGENICITY: Seroconversion: levels of antibody before and after immunization; Geometric mean titer (GMT): antibody titer following vaccination • EFFICACY: correlation between seroconversion and PROTECTION (Antibodies; CMI or both)Monday, September 10, 2012
  43. 43. SAFETY: ADVERSE REACTIONS • MILD: adverse reaction does not interfere with normal activities; may be bothersome • MODERATE: adverse reaction produces some impairment of functioning but NOT hazardous to health; uncomfortable or disturbing • SEVERE: adverse reaction produces significant impairment of functioning or incapacitation; a definite hazard to healthMonday, September 10, 2012
  44. 44. EFFICACY • Streptococcus pneumoniae; Neisseria meningitidis; Hemophilus influenzae capsular polysaccharide (85%) • Diphtheria and tetanus Toxoids (>90%) • Bordetella pertussis (whooping cough) (>90%) • Salmonella typhi (killed or live attenuated) (80%) • Mycobacterium tuberculosis (BCG) (0-70%)Monday, September 10, 2012
  45. 45. VACCINE- PREVENTABLE DISEASESMonday, September 10, 2012
  46. 46. VACCINES FOR YOU Following primary series of immunizations, young adults should have a further dose of TD at age 15-16 years Health care workers need evidence of two measles vaccinations or blood test conforming immunity Meningitis vaccination recommended for students & staff in residential colleges of the university or in any group accommodationMonday, September 10, 2012
  47. 47. VACCINES FOR YOU Following primary series of immunizations, young adults should have a further dose of TD at age 15-16 years Health care workers need evidence of two measles vaccinations or blood test conforming immunity Meningitis vaccination recommended for students & staff in residential colleges of the university or in any group accommodationMonday, September 10, 2012
  48. 48. VACCINES FOR YOU Following primary series of immunizations, young adults should have a further dose of TD at age Basic Vaccinations: 15-16 years Tetanus Diphtheria Health care workers need evidence of Polio Measles two measles vaccinations or blood Mumps test conforming immunity Rubella Hepatitis B Meningitis vaccination recommended Meningitis for students & staff in residential colleges of the university or in any group accommodationMonday, September 10, 2012
  49. 49. VACCINES FOR YOU • RUBELLA • Lyophilized preparation of highly attenuated Wistar RA 27/3 strain rubella virus propagated in human diploid cells • 0.5ml single dose , SC • Side effects: rashes, malaise, temperature elevation, cough, coryza, headache, transient arthralgia & arthritis with or w/o joint effusionMonday, September 10, 2012
  50. 50. VACCINES FOR YOU • RUBELLA • Lyophilized preparation of highly attenuated Wistar RA 27/3 strain rubella virus propagated in human diploid cells • 0.5ml single dose , SC • Side effects: rashes, malaise, temperature elevation, cough, coryza, headache, transient arthralgia & arthritis with or w/o joint effusionMonday, September 10, 2012
  51. 51. VACCINES FOR YOU • RUBELLA Basic Vaccinations: • Lyophilized preparation of highly Tetanus attenuated Wistar RA 27/3 strain Diphtheria rubella virus propagated in human Polio diploid cells Measles Mumps • 0.5ml single dose , SC Rubella Hepatitis B Meningitis • Side effects: rashes, malaise, temperature elevation, cough, coryza, headache, transient arthralgia & arthritis with or w/o joint effusionMonday, September 10, 2012
  52. 52. VACCINES FOR YOU • MMR • Live attenuated measles (Edmonston –Zagreb strain), mumps (Rubini strain), rubella (Wistar RA 27/3 strain) viruses. • Strains propagated on human diploid cells, no antibiotics • Vaccinate infants only after 15 months = Repeat immunization after 15 years for infants immunized before age 12 monthsMonday, September 10, 2012
  53. 53. VACCINES FOR YOU • MMR • Live attenuated measles (Edmonston –Zagreb strain), mumps (Rubini strain), rubella (Wistar RA 27/3 strain) viruses. • Strains propagated on human diploid cells, no antibiotics • Vaccinate infants only after 15 months = Repeat immunization after 15 years for infants immunized before age 12 monthsMonday, September 10, 2012
  54. 54. VACCINES FOR YOU • MMR • Live attenuated measles (Edmonston Basic Vaccinations: –Zagreb strain), mumps (Rubini Tetanus strain), rubella (Wistar RA 27/3 Diphtheria strain) viruses. Polio Measles • Strains propagated on human diploid Mumps cells, no antibiotics Rubella Hepatitis B • Vaccinate infants only after 15 Meningitis months = Repeat immunization after 15 years for infants immunized before age 12 monthsMonday, September 10, 2012
  55. 55. VACCINES FOR YOU • CHICKEN POX (VARICELLA) • Live attenuated varicella vaccine • For healthy infants from age 9 months onward, healthy subjects , high risk patients & healthy close contacts, patients with acute leukemia, under immunosuppressive treatment, patients with planned organ transplantation, patients with chronic diseases & healthy close contacts • Dose recommended: 2 doses 4-6 weeks apart for adultsMonday, September 10, 2012
  56. 56. VACCINES FOR YOU • CHICKEN POX (VARICELLA) • Live attenuated varicella vaccine • For healthy infants from age 9 months onward, healthy subjects , high risk patients & healthy close contacts, patients with acute leukemia, under immunosuppressive treatment, patients with planned organ transplantation, patients with chronic diseases & healthy close contacts • Dose recommended: 2 doses 4-6 weeks apart for adultsMonday, September 10, 2012
  57. 57. VACCINES FOR YOU • CHICKEN POX (VARICELLA) Additional • Live attenuated varicella vaccine Vaccinations: • For healthy infants from age 9 months Chicken pox onward, healthy subjects , high risk Hepatitis A patients & healthy close contacts, patients Influenza Pertussis with acute leukemia, under immunosuppressive treatment, patients Salmonella typhi with planned organ transplantation, Cholera patients with chronic diseases & healthy Pneumonia close contacts • Dose recommended: 2 doses 4-6 weeks apart for adultsMonday, September 10, 2012
  58. 58. VACCINES FOR YOU • HEPATITIS A • Inactivated hepatitis A virus for individuals > 15 years of age in pre-filled syringe • Virosomal hepatitis A virus antigen (RG-SB strain) for adults & children over 12 months • Basic immunization : Intramuscular injection • Booster immunization: 6, 12 or 18 months after first immunization • Simultaneous active & passive immunization at another siteMonday, September 10, 2012
  59. 59. VACCINES FOR YOU • HEPATITIS A • Inactivated hepatitis A virus for individuals > 15 years of age in pre-filled syringe • Virosomal hepatitis A virus antigen (RG-SB strain) for adults & children over 12 months • Basic immunization : Intramuscular injection • Booster immunization: 6, 12 or 18 months after first immunization • Simultaneous active & passive immunization at another siteMonday, September 10, 2012
  60. 60. VACCINES FOR YOU • HEPATITIS A Additional • Inactivated hepatitis A virus for individuals > Vaccinations: 15 years of age in pre-filled syringe Chicken pox • Virosomal hepatitis A virus antigen (RG-SB Hepatitis A strain) for adults & children over 12 Influenza months Pertussis • Basic immunization : Intramuscular Salmonella typhi injection Cholera • Booster immunization: 6, 12 or 18 months Pneumonia after first immunization • Simultaneous active & passive immunization at another siteMonday, September 10, 2012
  61. 61. VACCINES FOR YOU • INFLUENZA • Highly purified surface antigens of influenza viruses types A & B constituted strains annually recommended by WHO • Polyvalent whole virus vaccine against strains of groups A & B • Purified split inactivated influenza virusMonday, September 10, 2012
  62. 62. VACCINES FOR YOU • INFLUENZA • Highly purified surface antigens of influenza viruses types A & B constituted strains annually recommended by WHO • Polyvalent whole virus vaccine against strains of groups A & B • Purified split inactivated influenza virusMonday, September 10, 2012
  63. 63. VACCINES FOR YOU • INFLUENZA Additional Vaccinations: • Highly purified surface antigens Chicken pox of influenza viruses types A & Hepatitis A B constituted strains Influenza annually recommended by Pertussis WHO Salmonella typhi • Polyvalent whole virus vaccine Cholera Pneumonia against strains of groups A & B • Purified split inactivated influenza virusMonday, September 10, 2012
  64. 64. VACCINES FOR YOU • CHOLERA • Orochol E Berna contains not < 2x109 viable organisms of the attenuated strain Vibrio CVD 103-HgR in a lyophilized form • For ORAL active immunization of adults & children >2 years against cholera • Dosage: Resuspend contents of both chambers at the same time in cold or lukewarm water, mix carefully for 5-10 seconds & drink immediately. • Do not resuspend in milk, juice or carbonated beverages.Monday, September 10, 2012
  65. 65. VACCINES FOR YOU • CHOLERA • Orochol E Berna contains not < 2x109 viable organisms of the attenuated strain Vibrio CVD 103-HgR in a lyophilized form • For ORAL active immunization of adults & children >2 years against cholera • Dosage: Resuspend contents of both chambers at the same time in cold or lukewarm water, mix carefully for 5-10 seconds & drink immediately. • Do not resuspend in milk, juice or carbonated beverages.Monday, September 10, 2012
  66. 66. VACCINES FOR YOU • CHOLERA • Orochol E Berna contains not < 2x109 viable organisms of the attenuated strain Vibrio CVD 103-HgR in a lyophilized form Additional Vaccinations: • For ORAL active immunization of adults & Chicken pox children >2 years against cholera Hepatitis A Influenza Pertussis • Dosage: Resuspend contents of both chambers at the same time in cold or Salmonella typhi lukewarm water, mix carefully for 5-10 Cholera seconds & drink immediately. Pneumonia • Do not resuspend in milk, juice or carbonated beverages.Monday, September 10, 2012
  67. 67. VACCINES FOR YOU • TYPHOID • Vi capsular polysaccharide typhoid vaccine: Single IM or SC injection • Oral Vaccine preparation > 109 viable organisms of attenuated Salmonella typhi strain Ty21a Berna; has cross immunity against S. paratyphi BMonday, September 10, 2012
  68. 68. VACCINES FOR YOU • TYPHOID • Vi capsular polysaccharide typhoid vaccine: Single IM or SC injection • Oral Vaccine preparation > 109 viable organisms of attenuated Salmonella typhi strain Ty21a Berna; has cross immunity against S. paratyphi BMonday, September 10, 2012
  69. 69. VACCINES FOR YOU • TYPHOID Additional • Vi capsular polysaccharide Vaccinations: typhoid vaccine: Single IM or SC Chicken pox injection Hepatitis A Influenza Pertussis • Oral Vaccine preparation > 109 Salmonella typhi viable organisms of attenuated Cholera Pneumonia Salmonella typhi strain Ty21a Berna; has cross immunity against S. paratyphi BMonday, September 10, 2012
  70. 70. VACCINES FOR YOU • PNEUMOCOCCUS • Purified polysaccharide of Streptococcus pneumoniae • 25ug each of 23 serotypes: 1,2,3,4,5,6B,7F,8,9V,10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, 33F • Indications: Prevention of pneumococcal infections, particularly those of respiratory origin for ages over 2 years who are at risk of serious pneumococcal infectionMonday, September 10, 2012
  71. 71. VACCINES FOR YOU • PNEUMOCOCCUS • Purified polysaccharide of Streptococcus pneumoniae • 25ug each of 23 serotypes: 1,2,3,4,5,6B,7F,8,9V,10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, 33F • Indications: Prevention of pneumococcal infections, particularly those of respiratory origin for ages over 2 years who are at risk of serious pneumococcal infectionMonday, September 10, 2012
  72. 72. VACCINES FOR YOU • PNEUMOCOCCUS • Purified polysaccharide of Streptococcus pneumoniae Additional Vaccinations: Chicken pox • 25ug each of 23 serotypes: Hepatitis A 1,2,3,4,5,6B,7F,8,9V,10A, 11A, 12F, 14, Influenza 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, Pertussis 33F Salmonella typhi • Indications: Prevention of pneumococcal Cholera infections, particularly those of Pneumonia respiratory origin for ages over 2 years who are at risk of serious pneumococcal infectionMonday, September 10, 2012
  73. 73. VACCINES FOR YOU • PNEUMOCOCCUS • Dosage: Initial Injections: Single IM or SC injection confers protection against the 23 types of pneumococci in the vaccine • Revaccination should not be carried out for at least 5 years as severe local reactions (Arthus phenomena type) were observed if time between 2 injections is too shortMonday, September 10, 2012
  74. 74. VACCINES FOR YOU • PNEUMOCOCCUS • Dosage: Initial Injections: Single IM or SC injection confers protection against the 23 types of pneumococci in the vaccine • Revaccination should not be carried out for at least 5 years as severe local reactions (Arthus phenomena type) were observed if time between 2 injections is too shortMonday, September 10, 2012
  75. 75. VACCINES FOR YOU • PNEUMOCOCCUS • Dosage: Initial Injections: Single Additional IM or SC injection confers Vaccinations: Chicken pox protection against the 23 types of Hepatitis A pneumococci in the vaccine Influenza Pertussis • Revaccination should not be Salmonella typhi carried out for at least 5 years as Cholera severe local reactions (Arthus Pneumonia phenomena type) were observed if time between 2 injections is too shortMonday, September 10, 2012
  76. 76. ISSUES TO CONSIDER • Which vaccine to administer to whom? • When to vaccinate: months before exposure? • How many doses? Cost? • Interval between doses in case of multi-dose regimen for primary immunization • When to expect protection? Immunologic response vs protection? • Possibility of adverse/side effectsMonday, September 10, 2012
  77. 77. EXPANDED IMMUNIZATION PROGRAMSMonday, September 10, 2012
  78. 78. The 7 EPI Diseases Measles Diphtheria Poliomyelitis Hepatitis B Pertussis Tetanus TuberculosisMonday, September 10, 2012
  79. 79. 1976 Official launching of EPI in the Philippines 1977 BCG & DPT2 for infants in priority areas BCG & DPT2 expanded nationwide 1979 OPV3 in selected areas reporting outbreaks TT2 for pregnant women at 5 months gestation 1980 OPV3 & TT2 given nationwide 1982 Measles vaccine for 35% of the population 1983 Measles vaccination given nationwide 1984 DPT3 added; TT given anytime during pregnancy 1985 Comprehensive Program ReviewMonday, September 10, 2012
  80. 80. 1986 Universal Child Immunization Goal by 1990-UN Start of Rotary International mass campaigns –Polio 1987 Plus TT3, TT4, TT5 added; Wednesday adopted as 1989 Immunization Day National Plan of Action for Polio Eradication 1991 launched; Polio Eradication Unit 1992 Hepatitis B immunization -40% of infants 1993 1st National Immunization Days Neonatal Tetanus Elimination-Action Plan Measles Control – National Plan of ActionMonday, September 10, 2012
  81. 81. Bacteria Disease Antigen Efficacy Streptococcus Capsular Pneumonia 85% pneumoniae polysaccharide Neisseria Capsular meningitis 85% meningitidis polysaccharide Hemophilus Capsular meningitis 85% influenzae polysaccharide Corynebacterium Diphtheriae Toxoid >90% diphtheriae Clostridium tetani tetanus Toxoid >90% Bordetella Whooping cough Killed organism >90% pertussis Mycobacterium Tuberculosis Live attenuated 0 – 70 % bovis (BCG) Killed/Live Salmonella typhi Typhoid fever 80% attenuatedMonday, September 10, 2012
  82. 82. Vaccine Reason for Immunization Given at the earliest possible age protects BCG against the possibility of infection from family members Early start with DPT reduces chance of DPT severe pertussis Protection against polio increased the OPV earlier the OPV is given Early start of HBV vaccination reduces Hepatitis B chance of being infected and becoming a carrier At least 80% of measles can be prevented Measles by immunization at this ageMonday, September 10, 2012
  83. 83. Diseases to be immunized Age against Birth Tuberculosis 6 weeks DPT; Polio; HBV 10 weeks DPT; Polio; HBV 14 weeks DPT; Polio; HBV 9 months MeaslesMonday, September 10, 2012
  84. 84. Tetanus toxoid Immunization Schedule for Women Percent Vaccine Minimum age/interval Duration of protection protected As early as possible during TT1 pregnancy * Infants born to the mother protected from TT2 At least 4 weeks later 80% neonatal tetanus; 3 years protection to mother * Infants protected; TT3 At least 6 months later 95% 5 years protection to mother * Infants protected; TT4 At least one year later 99% 10 years protection to mother Lifetime protection for mother; * all infants born TT5 At least one year later 99% to that mother will be protectedMonday, September 10, 2012
  85. 85. Philippine Immunization Flagship Programs  Poliomyelitis Eradication  Measles Elimination  Maternal and Neonatal Tetanus Elimination  Control of Hepatitis BMonday, September 10, 2012
  86. 86. TAKE-HOME QUIZ • Next to Smallpox, why do you think that polio and measles are the next diseases targeted for global elimination? • Differentiate the 4 Immunization Flagship Programs of the country in terms of: • target group, vaccine to use and route, criteria for successMonday, September 10, 2012
  87. 87. IMMUNOLOGIC TOLERANCE AND AUTOIMMUNITYMonday, September 10, 2012
  88. 88. RECALL... • Immunologic tolerance: unresponsiveness to self-antigens • WHAT WE WILL LEARN: • How does the immune system maintain its unresponsiveness to self-antigens • What are the factors that may contribute to the development of autoimmunity?Monday, September 10, 2012
  89. 89. ON ENCOUNTER WITH LYMPHOCYTES...Monday, September 10, 2012
  90. 90. ON ENCOUNTER WITH LYMPHOCYTES... The choice among lymphocyte activation, tolerance, and ignorance is determined by the nature of the antigen-specific lymphocytes and by the nature of the antigen and how it is displayed to the immune systemMonday, September 10, 2012
  91. 91. IMPORTANCE OF IMMUNOLOGIC TOLERANCE • the knowledge that self-antigens normally induce tolerance • if we learn how to induce tolerance in lymphocytes specific for a particular antigen, we may be able to use this knowledge to prevent or control unwanted immune reactions • APPLICATIONS: • treat allergic and autoimmune diseases • prevent the rejection of organ transplants • gene therapy • prevent immune responses against the products of newly expressed genes or vectorsMonday, September 10, 2012
  92. 92. CENTRAL & PERIPHERAL • central tolerance: induced when developing lymphocytes encounter these antigens in the generative lymphoid organs (bone marrow and thymus) • peripheral tolerance: induces when mature lymphocytes encounter self antigens in peripheral tissuesMonday, September 10, 2012
  93. 93. AUTOIMMUNITY • Principal factors in the development of autoimmunity: • inheritance of susceptibility genes • may contribute to failure of self-tolerance • environmental triggers • e.g. infections = may activate self-reactive lymphocytesMonday, September 10, 2012
  94. 94. CENTRAL T-LYMPHOCYTE TOLERANCE • Negative selection: principal mechanism of central tolerance • Strong recognition of self antigens immature T-cells in the thymus may lead to death of the cells (negative selection or deletion) • Self-antigen recognition in the thymus may also lead to the development of regulatory T- cells that enter peripheral tissuesMonday, September 10, 2012
  95. 95. PERIPHERAL T- LYMPHOCYTES & ANERGY • Peripheral tolerance: • induced when mature T cells recognize self antigens in peripheral tissues, leading to functional inactivation (anergy) or death • induced when the self-reactive lymphocytes are suppressed by regulatory T cellsMonday, September 10, 2012
  96. 96. ANERGY • ANERGY: functional inactivation of T-lymphocytes that occurs when these ceIls recognize antigens without adequate levels of the costimulators (second signals) that are needed for full T-cell activationMonday, September 10, 2012
  97. 97. ACTIVATION-INDUCED CELL DEATH : DELETIONMonday, September 10, 2012
  98. 98. IMMUNE SUPPRESSIONMonday, September 10, 2012
  99. 99. Characteristics of self and foreign (e.g. microbial) protein antigens that determine why the self antigens induce tolerance and microbial antigens stimulate T-cell mediated immune responsesMonday, September 10, 2012
  100. 100. CENTRAL TOLERANCE IN B-CELLSMonday, September 10, 2012
  101. 101. PERIPHERAL TOLERANCE IN B-CELLSMonday, September 10, 2012
  102. 102. AUTOIMMUNE DISEASES & MHC MOLECULESMonday, September 10, 2012
  103. 103. Monday, September 10, 2012
  104. 104. MOLECULAR MIMICRY & AUTOIMMUNITYMonday, September 10, 2012
  105. 105. SUMMARY • Immunologic tolerance: specific unresponsiveness to an antigen induced by exposure of lymphocytes to that antigen • All individuals are tolerant of (unresponsive to) their own (self)antigens • Tolerance against antigens may be induced by administering that antigen in particular ways = strategy may be useful for treating immunologic disease and for preventing the rejection of transplantsMonday, September 10, 2012
  106. 106. SUMMARY • Autoimmune diseases: result from a failure of self- tolerance • Multiple factors contribute to autoimmunity: • immunologic abnormalities • susceptibility genes • infectionsMonday, September 10, 2012
  107. 107. SUMMARY • Central tolerance: induced by the death of immature lymphocytes that encounter antigens in the generative lymphoid organs while Peripheral tolerance: results from the recognition of antigens by mature Iymphocytes in peripheral tissues • T-CELLS: • Central tolerance (negative selection): result of high- affinity recognition of antigens in the thymus, which tend to be widely disseminated self-antigens AND may eliminate the potentially most dangerous T-cells, which express high- affinity receptors for disseminated self-antigensMonday, September 10, 2012
  108. 108. SUMMARY • T-CELLS: • Peripheral tolerance: induced by multiple mechanisms • Anergy (functional inactivation) results from the recognition of antigens without costimulators (second signals) or when T cells use inhibitory receptors to recognize costimulators • Deletion (death by apoptosis) occurs when T cells repeatedly encounter self antigens • Some self-reactive T cells suppress potentially pathogenic T-cellsMonday, September 10, 2012
  109. 109. SUMMARY •B-CELLS • central tolerance: induced when immature cells recognize self antigens in the bone marrow • peripheral tolerance: (by anergy) induced when mature B cells recognize self antigens without T cell helpMonday, September 10, 2012
  110. 110. SUMMARY • AUTOIMMUNITY • Many genes contribute to the development of autoimmunity • The strongest associations are between HLA genes and various T cell-mediated autoimmune diseases • Infections predispose to autoimmunity, by causing inflammation and inducing the aberrant expression of costimulators or because of cross-reactions between microbial and self antigensMonday, September 10, 2012
  111. 111. vanderbilt.edu IMMUNE RESPONSE AGAINST TUMORS/TRANSPLANTS Reference; Immunology by AbbasMonday, September 10, 2012
  112. 112. CALENDAR FOR BIO 151 DATE ACTIVITY September 11 TUMORS, TRANSPLANTS & SERODIAGNOSIS September 18 EXAMINATION 2 (VACCINES TO SEROLOGICAL DIAGNOSTICS) September 25- October 2 IMMUNITY TO MICROBIAL INFECTIONS: Pneumonia a.Fungi b.Virus c.Bacteria IMMUNITY TO MICROBIAL INFECTIONS: Schistosomiasis October 9 EXAMINATION 3: Take-Home (24 hours) Questions available October 9, 2012 at 12 noon...Submission should be October 10, 2012 at 12 noon (at DB, received and stamped by DB staff) *** Printed and well-citedMonday, September 10, 2012
  113. 113. WHAT ARE TUMORS? webmd.com • Simply means a mass of cells • Can be either benign or malignant • Benign tumors: not a threat to life or long- term health; made up of related but different cells • Malignant tumors: threat to life or long- term health; clonal or all identical to the cell of originMonday, September 10, 2012
  114. 114. IMMUNE RESPONSE TO TUMORS • T cells generally mount effective surveillance against tumors associated with oncogenic viruses or UV induction (these are strongly immunogenic) • More weakly immunogenic tumors are not controlled by joseph-birch.livejournal.com T cell surveillance, although sometimes low grade responses are evokedMonday, September 10, 2012
  115. 115. IMMUNE RESPONSE TO TUMORS • NK cells play a role in containing tumor growth and metastases; • The importance of the immune system in preventing tumor growth can be seen in immunocompromised patients - AIDS patients have a much higher chance of developing many types of cancerMonday, September 10, 2012
  116. 116. WHAT IS CANCER? • diseases in which there is loss of regulation of the proliferative process • characterized by excessive, uncontrolled growth of abnormal cells, which invade and destroy other tissues nursingcrib.com • hyperproliferation of cells that have violated the basic rules of social cell behavior (i.e, lost the ability to be controlled by normal cell signals)Monday, September 10, 2012
  117. 117. CANCER • Control is important to ensure that cells only divide when needed (organs and tissues should maintain their correct shapes and sizes) • Should this system fail, several backup safety mechanisms prevent topnews.in the cell from dividing uncontrollablyMonday, September 10, 2012
  118. 118. DEFENSE AGAINST UNCONTROLLED PROLIFERATION • A cell can initiate cell death (suicide) when a defect is detected through a process called apoptosis • A cell can repair the error and become a normal cell genengnews.com • Immune system (e.g., natural killer cells can detect abnormal cells and kill them)Monday, September 10, 2012
  119. 119. WHAT ARE ORGANS TRANSPLANTS? • surgical operation in which a failing or damaged organ in the human body is removed and replaced with a functioning one • donated organ may be from a deceased donor, a living donor, or an animal • NOTE: In some cases an artificial organ is usedMonday, September 10, 2012
  120. 120. WHAT ARE ORGANS TRANSPLANTS? • Cadaveric organ donation involves removing organs from a recently deceased donor • Living organ donation involves the donation of one of a paired organ (such as kidneys) or a portion of an organ (such as a lobe of the liver or lung) • The donors organ system is still able to function after the donation • Living donors are often related to the patient, but that is not always the caseMonday, September 10, 2012
  121. 121. SO WHAT’S IT FOR IMMUNOLOGY? • CANCER: enhancing immunity against the tumors holds much promise for treatment •TRANSPLANTS: immune responses against transplants are a barrier for a successful transplantationMonday, September 10, 2012
  122. 122. WHAT WE WILL LEARN... • What are the antigens in tumors and tissue transplants that are recognized as foreign by the immune system? • How does the immune system recognize and react to tumors and transplants? • How can the immune responses to tumors and grafts be manipulated to enhance tumor rejection and inhibit graft rejection?Monday, September 10, 2012
  123. 123. IMMUNE SURVEILLANCE • 1950s: a physiologic function of the adaptive immune system is to prevent the outgrowth of transformed cells or to destroy these cells before they become harmful tumors london-research-institute.org.uk aihealthsolutions.caMonday, September 10, 2012
  124. 124. EVIDENCES SUPPORTING THE CONCEPT OF IMMUNO SURVEILLANCEMonday, September 10, 2012
  125. 125. TUMOR ANTIGENS • Malignant tumors express various types of molecules that may be recognized by the immune system as foreign antigensMonday, September 10, 2012
  126. 126. IMMUNE MECHANISM FOR TUMOR REJECTION • The principal immune mechanism of tumor eradication is killing of tumor cells by cytolytic T-lymphocytes (CTLs) specific for tumor antigens • endogenously synthesized cytosolic proteins displayed as Class I MHC-associated peptides • SO: recognized by class I MHC-restricted CD8+ CTLs (kills the cell producing the antigens)Monday, September 10, 2012
  127. 127. IMMUNE MECHANISM FOR TUMOR REJECTION • CTLs responses against tumor cells are often induced by recognition of tumor antigens on host-antigen presenting cells (APCs) which ingest tumor cells or their antigens and present the antigens to T-cellsMonday, September 10, 2012
  128. 128. IMMUNE MECHANISM FOR TUMOR REJECTION • anti-tumor CD4+ T- cell responses and antibodies have been detected in patients (but may not be protective) • activated macrophages and NK cells are capable of killing tumor cells in vitro (unclear protection)Monday, September 10, 2012
  129. 129. EVASION OF IMMUNE RESPONSE BY TUMORS • Immune response often fail to check tumor growth because these responses are ineffective or because tumors evolve to evade immune attack • Immune responses against tumors may be weak because many tumor antigens are weakly immunogenic, perhaps because they differ only slightly from self antigensMonday, September 10, 2012
  130. 130. EVASION OF IMMUNE RESPONSE BY TUMORS • Growing tumors also develop mechanisms for evading immune responses • stop expressing the antigens that are targets of immune attack (antigen loss variants) = continue to grow and spread • stop expressing class I MHC molecules = cannot display antigens to CD8+ T-cells (cross- priming) • may produce molecules, e.g. transforming growth factor-beta, that suppress immuneMonday, September 10, 2012 responses
  131. 131. IMMUNOTHERAPY FOR TUMORS • MAIN GOAL: • provide antitumor effectors (antibodies and T-cells) to patients • actively immunize patients against their tumors • stimulate the patients’ own antitumor immune responseMonday, September 10, 2012
  132. 132. IMMUNOTHERAPY VS CHEMOTHERAPY • Chemotherapy/ Irradiation: may have devastating effects on normal non-tumor tissues • Immunotherapy: highly- specific for the tumor health.umn.eduMonday, September 10, 2012
  133. 133. STRATEGY 1: PASSIVE IMMUNITY • immune effectors are injected into cancer patients • e.g. monoclonal antibodies to tumor antigens + potent toxins • HOW: antibodies bind to tumor antigens and activate host effector mechanisms (e.g. phagocytes or complement system) • HOW: toxins delivered to tumor cellsMonday, September 10, 2012
  134. 134. EXAMPLE: BREAST CANCER IMMUNOTHERAPY • ALL information from: Critical Reviews in Oncology and Hematology, October 2010 (Emde et al. Therapeutic strategies and mechanisms of tumorigenesis of HER2-overexpressing breast cancer) • HER2 (tyrosine kinase): overexpressed in approximately 25% of breast cancers; acts as a signal amplifier for its siblings = transmembrane receptors that collectively bind with 11 distinct growth factors of the EGF family • THUS: overexpression of HER2 confers aggressive invasive growth in preclinical models and in patients • “Specific therapies targeting HER2 include monoclonal antibodies, antibody–drug conjugates, small molecule tyrosine kinase inhibitors, as well as heat shock protein and sheddase inhibitors. Two of these drugs have shown impressive – yet mostly transient – efficacy in patients with HER2 overexpressing breast cancer.”Monday, September 10, 2012
  135. 135. Signal transduction pathways instigated by HER2, co-receptors and EGF-like growth factors (epidermal) and NRGs (neuregulins)Monday, September 10, 2012
  136. 136. Clinically approved and experimental therapeutic strategies targeting ErbB-2/ HER2 in carcinomas: a. Trastuzumab: humanized monoclonal antibody directed against the extracellular domain of HER2; recruits immune effector mechanisms and can induce apoptosis, block angiogenesis and inhibit tumor cell proliferation. b. Pertuzumab: prevent heterodimerization of HER2 with other family members RECENTS: a. Lapatinib: tyrosine kinase inhibitors; reversible inhibitor b. Neratinib: irreversible inhibitor; variably inhibit a broad range of tyrosine kinases c. 17-AAG: block the ATP/ADP binding pocket of HSP90 and target HER2 for proteasomal degradation (Note; HSP90: molecular chaperone required for proper folding of protein kinases like HER2Monday, September 10, 2012
  137. 137. STRATEGIES FOR ENHANCING ANTITUMOR IMMUNE RESPONSE • 1. Tumor- antigen pulsed DC: mimic normal pathway of cross- presentation to induce specific T-cell responseMonday, September 10, 2012
  138. 138. STRATEGIES FOR ENHANCING ANTITUMOR IMMUNE RESPONSE • 2. DNA or transfected DC: the host produce the tumor antigen thus inducing specific T- cell responseMonday, September 10, 2012
  139. 139. STRATEGIES FOR ENHANCING ANTITUMOR IMMUNE RESPONSE • 3. tumor cell expressing costimulators (e.g. B7) or cytokines (e.g. IL-2): cytokines or costimulators to stimulate the generation of own tumor-specific immune responseMonday, September 10, 2012
  140. 140. IMMUNE RESPONSE AGAINST TRANSPLANTSMonday, September 10, 2012
  141. 141. IMMUNE RESPONSE AGAINST TRANSPLANTS • transplants exchanged wenliang.myweb.uga.edu between animals of the same and other inbred are accepted • grafts among different strains are rejected • GENES for graft rejection: products are expressed in ALL tissuesMonday, September 10, 2012
  142. 142. IMMUNE RESPONSE AGAINST TRANSPLANTS • Allogeneic (allografts) and Xenogeneic (xenografts) grafts are always rejected • Alloantigens (alloreactive antibodies and T-cells) • Xenoantigens (xenoreactive antobodies and T-cells) • CLINICAL Scenario: mostly allogeneicMonday, September 10, 2012
  143. 143. Transplantation Antigens • The antigens of allografts that serve as the principal targets of rejection are proteins encoded in the MHC • Human MHC = human leukocyte antigen or HLAMonday, September 10, 2012
  144. 144. INDUCTION OF IMMUNE RESPONSES AGAINST TRANSPLANTS • T-cells may recognize allogeneic MHC molecules in the graft by professional APCs, or graft alloantigens may be processed and presented by hosts’ professional APCsMonday, September 10, 2012
  145. 145. INDUCTION OF IMMUNE RESPONSES AGAINST TRANSPLANTS • T-cells may recognize allogeneic MHC molecules if the graft does not contain professional APCs, how does it stimulate T cells? in the graft by professional APCs, or graft alloantigens may be processed and presented by hosts’ professional APCsMonday, September 10, 2012
  146. 146. INDUCTION OF IMMUNE RESPONSES AGAINST TRANSPLANTS • T-cells may recognize allogeneic MHC molecules if the graft does not contain professional APCs, how does it stimulate T cells? in the graft by professional APCs, or graft alloantigens may be processed and presented by hosts’ graft cells are ingested by professional APCs in the recipient and professional the donor alloantigens are processed and presented by the self MHC molecules on recipient APCs APCsMonday, September 10, 2012
  147. 147. MIXED LYMPHOCYTE REACTION (MLR) wenliang.myweb.uga.edu • an in vitro model of T-cell recognition in alloantigensMonday, September 10, 2012
  148. 148. MIXED LYMPHOCYTE REACTION (MLR) • T-cells from one individual are cultured with leukocytes of another individual and the responses of the T-cells are assayed • magnitude of response is proportional to the extent of MHC differences between these individuals • rough predictor of the outcomes of grafts exchanged between these individualsMonday, September 10, 2012
  149. 149. IMMUNE MECHANISM OF GRAFT REJECTION • occurs within minutes of transplantation; characterized by thrombosis of graft vessels and ischemic necrosis of the graft • mediated by circulating antibodies specific for antigens on graft endothelial cellsMonday, September 10, 2012
  150. 150. IMMUNE MECHANISM OF GRAFT REJECTION not common BUT major barrier to xenotransplantation • occurs within minutes of transplantation; characterized by thrombosis of graft vessels and ischemic necrosis of the graft • mediated by circulating antibodies specific for antigens on graft endothelial cellsMonday, September 10, 2012
  151. 151. IMMUNE MECHANISM OF GRAFT REJECTION • occurs within days or weeks after transplantation • principal cause of early graft failure • mediated mainly y T-cells which react against alloantigens in the graft or may react agains cells in graft vessels leading to vascular damageMonday, September 10, 2012
  152. 152. IMMUNE MECHANISM OF GRAFT REJECTION antibodies may also play a role • occurs within days or weeks after transplantation • principal cause of early graft failure • mediated mainly y T-cells which react against alloantigens in the graft or may react agains cells in graft vessels leading to vascular damageMonday, September 10, 2012
  153. 153. IMMUNE MECHANISM OF GRAFT REJECTION • occurs over months or years that leads to progressive loss of graft function • manifested as fibrosis or narrowing of vessels (arteriosclerosis) • T-cells secrete cytokines which stimulate proliferation of fibroblasts and vascular smooth muscle cells in the graftMonday, September 10, 2012
  154. 154. PREVENTION & TREATMENT OF GRAFT REJECTION e-steroid.comMonday, September 10, 2012
  155. 155. BONE MARROW TRANSPLANTS • elicit strong rejection reactions: must perform cross- matches • carry the risk of graft-versus- host disease: If mature allogeneic T cells are transplanted with the marrow cells, these mature T cells can attack the recipients tissues • lead to temporary immunodeficiency in recipientsMonday, September 10, 2012
  156. 156. QUESTIONS?Monday, September 10, 2012
  157. 157. elitechgroup.com SERODIAGNOSIS Reference; Jawetz Medical Microbiology (http://accessmedicine.com/resourceTOC.aspx?resourceID=6)Monday, September 10, 2012
  158. 158. ehrs.upenn.edu BIOSAFETY 2008.igem.org busytrade.comMonday, September 10, 2012
  159. 159. OVERVIEW OF DIAGNOSTICS • 3 CATEGORIES: • Direct: clinical specimen is examined directly for the presence of virus particles, virus antigen or viral nucleic acids • Indirect: the specimen into cell culture, eggs or animals in an attempt to grow the virus • Serology: detection of rising titres of antibody between acute and convalescent stages of infection, or the detection of IgMonday, September 10, 2012
  160. 160. ANTIGEN DETECTION: DIRECT • Applications: • immunofluorescence testing of nasopharyngeal aspirates for respiratory viruses e.g.. RSV, flu A, flu B, and adenoviruses • detection of rotavirus antigen in fecesrotavirus, adenovirus, astroviruses, Norwalk-like viruses • the pp65 CMV antigenaemia test • the detection of HSV and VZV in skin scrapingMonday, September 10, 2012
  161. 161. ANTIGEN DETECTION: DIRECT geneaid.com wclassproducts.com norgenbiotek.comMonday, September 10, 2012
  162. 162. ANTIGEN DETECTION: INDIRECTMonday, September 10, 2012
  163. 163. ANTIGEN DETECTION: INDIRECT (enhanced)Monday, September 10, 2012
  164. 164. ANTIBODY DETECTION: SEROLOGY http://virology-online.com usada.orgMonday, September 10, 2012
  165. 165. COMMON TESTS • Classical Techniques: • Newer Techniques: • Complement fixation tests • Radioimmunoassay (RIA) (CFT) • Enzyme linked • Hemagglutination inhibition immunosorbent assay (EIA) tests (HAI) • Particle agglutination • Immunofluorescence techniques (IF) • Western Blot (WB) • Neutralization tests • Recombinant immunoblot assay (RIBA) • Single Radial HemolysisMonday, September 10, 2012
  166. 166. DIAGNOSING A PRIMARY (ACUTE) INFECTION • A significant rise in titre of IgG/total antibody between acute and convalescent sera • CFT and HAI, it is normally taken as a four-fold or greater increase in titre • diagnosis is usually retrospective because by the time the convalescent serum is taken, the patient had probably recoveredMonday, September 10, 2012
  167. 167. DIAGNOSING A PRIMARY (ACUTE) INFECTION • Presence of IgM • EIA, RIA, and IF may be used (rapid) • BUT: • interference by rheumatoid factor, • re-infection by the virus • unexplained persistence of IgM years after the primary infectionMonday, September 10, 2012
  168. 168. DIAGNOSING A PRIMARY (ACUTE) INFECTION • Seroconversion • changing from a previously antibody negative state to a positive state • e.g. seroconversion against HIV following a needle- stick injury, or against rubella following contact with a known caseMonday, September 10, 2012
  169. 169. DIAGNOSING A PRIMARY (ACUTE) INFECTION • A single high titre of IgG (or total antibody) • this is a very unreliable means of serological diagnosis since the cut-off is very difficult to defineMonday, September 10, 2012
  170. 170. DIAGNOSING A RE- INFECTION / RE-ACTIVATION • It is often very difficult to differentiate re-infection/re- activation from a primary infection • When important: rubella infection in the first trimester of pregnancy: primary infection is associated with a high risk of fetal damage whereas re-infection is not • RE-INFECTION: sharp large rise in antibody titres • RE-INFECTION/ RE-ACTIVATION: IgM is usually low or absentMonday, September 10, 2012
  171. 171. USE DEPENDS ON PATHOGEN • onset of clinical symptoms coincide with the development of antibodies: e.g. rubella and hepatitis A (IgM or rising titres of IgG in the serum of the patient would indicate active disease) • pathogen produce clinical disease before the appearance of antibodies: e.g. respiratory and diarrheal viruses (serological diagnosis would be retrospective and therefore will not be that useful) • pathogen produce clinical disease months or years after seroconversion: e.g. HIV and rabies (the mere presence of antibody is sufficient to make a definitive diagnosis)Monday, September 10, 2012
  172. 172. READING ASSIGNMENT: Q: WHAT DO YOU THINK ARE SOME PROBLEMS WITH SEROLOGYMonday, September 10, 2012
  173. 173. medicineworld.org THE SEROLOGICAL immunology.utoronto.ca DIAGNOSTICSMonday, September 10, 2012
  174. 174. COMPLEMENT FIXATION TEST http://virology-online.com path.cam.ac.uk dshs.state.tx.usMonday, September 10, 2012
  175. 175. HEMAGGLUTINATION/ HEMAGGLUTINATION INHIBITION TESTS (HAI) motifolio.com virology.wsMonday, September 10, 2012
  176. 176. HEMAGGLUTINATION/ HEMAGGLUTINATION INHIBITION TESTS (HAI) qmark2.leeds.ac.uk path.cam.ac.ukMonday, September 10, 2012
  177. 177. IMMUNOFLUORESCENCE TECHNIQUE (IF) • DIRECT: known labeled antibody interacts with unknown antigen • INDIRECT: known antigen is attached to a slide, unknown serum is added and then washed = An/Ab fixed onto slide and can be detected by antibody-specific reagentMonday, September 10, 2012
  178. 178. IMMUNOFLUORESCENCE TECHNIQUE (IF) Respiratory Syncytial Virus (RSV) (a) Indirect technique: polyclonal rabbit serum and a conjugated sheep anti-rabbit serum; both were extensively absorbed to remove unwanted antibodies (b) Direct technique: mixture of three monoclonal conjugated antibodies and Evans blue counterstain (which, paradoxically, appears red) = staining only those antigenic concentrations for which there are antibodies in the mixture CREDITS: (Both micrographs were taken by Joyce McQuillin personally, SCIENCE DIRECT)Monday, September 10, 2012
  179. 179. NEUTRALIZATION TESTS • potential of the serum of neutralizing the biological http://www.sanidadanimal.info activity of an antigen can also be known • assessment of the capability of a serum against bacterial toxins, bacteria or viruses biobest.co.uk • laborious, need cell cultures, sterile conditions, and usually require more timeMonday, September 10, 2012
  180. 180. NEUTRALIZATION TESTS Positive MDCC-MSB1 infected cells culture showing fluorescence at the point where CAV antigen was detected biobest.co.uk culture negative to CAMonday, September 10, 2012
  181. 181. SINGLE RADIAL HEMOLYSIS • E.g. Rubella antibody. • LEFT PLATE: Control Plate • RIGHT PLATE: well in the middle of the plate contains the 15 miu/ml control serum = clear zone of lysis surrounding the well on the test plate which is absent on the control plate • NOTE: Specimens which gives a zone of lysis equal or greater than the 15 miu/ml control well are regarded as positive for rubella antibody. = Should a zone of similar size is present on the control plate, then the result is not validMonday, September 10, 2012
  182. 182. RADIOIMMUNOASSAY (RIA) • used to quantitate antigens or haptens taht can be radioactively-labeled • based on competition for specific antibody between the labeled (known) and the unlabeled (unknown) concentration of the material • complex that form between An/Ab can then be separated and the amount of radioactivity measuredMonday, September 10, 2012
  183. 183. RADIOIMMUNOASSAY (RIA) • concentration of the unlabeled (unknown) antigen or hapten is determined by comparing the results with those obtained using several concentrations of a predetermined standard antigen • highly sensitive for: • assay of hormones or drugs from serum • measure amount of IgE with known allergenMonday, September 10, 2012
  184. 184. users.rcn.comMonday, September 10, 2012
  185. 185. RADIOALLERGOSORBENT ASSAY (RAST) lookfordiagnosis.com pennstatehershey.adam.comMonday, September 10, 2012
  186. 186. ENZYME IMMUNOASSAY (EIA) • depends on the conjugation of an enzyme to either an antigen or an antibody • enzyme is detected by assaying for enzyme activity with its substrate • no need for radioactive labels piercenet.comMonday, September 10, 2012
  187. 187. ELISA technologyinscience.blogspot.com • can detect the ANTIGEN- ANTIBODY reaction by the use of enzyme- linked antibodies • based  on the use of labeled antibodies (usually done with the enzyme peroxidase) so that the resulting conjugates have both immunological  and enzymatic activityMonday, September 10, 2012
  188. 188. ELISA • one of the components of the conjugate (antibody or antigen) is attached to the plate, so the antigen-antibody reaction can be easily measured when adding the reaction substrate • This substrate produces a colored reaction product when it comes into contact with the enzyme • The color change can be seen or quantified with a colorimeterMonday, September 10, 2012
  189. 189. ELISA: ANTIGEN DETECTION • Sandwich ELISA • plates are usually coated with an antibody (monoclonal or polyclonal antibody) against the unknown antigen • sample that needs to be tested is added to the wells, and if the antigen is present, the antigen-antibody reaction will take place • add another antibody linked to an enzyme. • when the reaction substrate is added it turns a colorMonday, September 10, 2012
  190. 190. ELISA: ANTIBODY DETECTION • INDIRECT ELISA: coating of the ELISA plate with the antigen against the specific antibodies that may be present in the serum • NEXT: addition of serum, incubation and washing;  addition of the conjugate, incubation and washing and finally, the addition of the substrate, stopping the reaction and reading the resultsMonday, September 10, 2012
  191. 191. ELISA: ANTIBODY DETECTION • COMPETITIVE ELISA: have an antibody (monoclonal of polyclonal) of a known antigen which has previously been bound to the plate • competitive because the serum is incubated with the antigen previous to its incubation with the antiserum bound to the plate = both compete for the antigen • NEXT: addition of the conjugate, incubation, washing, and finally, substrate addition and reading the resultsMonday, September 10, 2012
  192. 192. ELISA & HIV virology-online.com hivinfosource.orgMonday, September 10, 2012
  193. 193. DENGUE SEROLOGYMonday, September 10, 2012
  194. 194. QUESTIONS?Monday, September 10, 2012
  195. 195. END OF EXAM 2 COVERAGEMonday, September 10, 2012
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