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VACCINE IMMUNOLOGY

VACCINE IMMUNOLOGY. Dr. Alişan Yıldıran. Terms. Ampiric: observational knowledge, could not explain how Adjuvant: increases stimulation of immune system Affinity maturation: maturation of the binding

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VACCINE IMMUNOLOGY

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  1. VACCINE IMMUNOLOGY Dr. Alişan Yıldıran Dr. Yildiran

  2. Terms • Ampiric: observational knowledge, could not explain how • Adjuvant: increases stimulation of immune system • Affinity maturation: maturation of the binding • Antigen presenting cell (APC) : phagocyte and shred the pathogen then, express on the membrane by MCH I and II • Germinal center: B cell transformes to plasma cell here, CSR and affinity maturation come true • Class switch recombination (CSR): IgM is converted to the other Ig’s • Inflamazome:provide links to innate immunity between TLR, NLP and capases (apoptosis). • Somatic Hypermutation (SHM): developing high sensitivity to an antigen • Toll like receptor (TLR): recognize some pattern peculiar to microbes an internsec danger signals then activates innate immune system • Polisaccaride:carbohydrate thatconstitutes bacterial membrane and capsule T-independent • Peptid: protein,T-dependent Dr. Yildiran

  3. Preventive Medicine • Prevention of a disease before its occurence. • Hygiene • Hand washing is the most important precaution for contamination. • Plague, leprosy • Immunization • Routine • Risk groub (travel, medical personnel) Katkı, 2006 Dr. Yildiran

  4. Lady Montagu • In 1716, she had been in İstanbul. • She wrote Letters from Turkey. She referred about swabbin to the children from smallpox patient. She also performed the same to her children. Dr. Yildiran

  5. In 1796, Jenner presented his vaccine that prepared from cows with smallpox • Vacca (Latin) cow • The second important person in vaccine history is Pasteur. • His laboratory that he developed vaccines od rabies and anthrax was supported by Sultan Abdülhamid. Katkı, 2006 Dr. Yildiran

  6. Non-specific immunity (Innate-ready) Immune System Specific immunity (Adaptive-Learned) Dr. Yildiran

  7. Immune Response Innate Adaptive Abbas, Immunology Dr. Yildiran

  8. Abbas, 2004 Dr. Yildiran

  9. Antigen presentation CD4 ≈ MHC II CD8 ≈ MHC I Dr. Yildiran

  10. Microbiome-Symbiosis • The human live together with too much useful bacterias that it is half of the body weight. • This universe formed by these microorganisms is called as microbiome. • Antibiotics and agents that affect immune system like vaccines have some effects on microbiome dynamics. Relman, 2012 Dr. Yildiran

  11. Mucosal immunity Dr. Yildiran

  12. Start of vaccine reponse If vaccine antigen is an enough danger signal, it activates dendritic cell and this cell migrates to lymph node. Dr. Yildiran Siegrist, 2008, WHO

  13. Germinal center and extrafolicular response to peptides Dr. Yildiran Siegrist, 2008, WHO

  14. Extrafolicular response • Naive B cells remain in the circulation to the antigen encounter. • When they encounter, these B cells go to the T cell region of lymphoid tissue by CCR7. • Here, they transforms to plasma cells with DC and Th cell help, then produce antibodies after CSR. • This is a short and low affinity prcess. Dr. Yildiran Siegrist, 2008, WHO

  15. Germinal center response • Here B cell maturation will be much stronger with the help of CXCR5 of folicular DC and CXCL13 of Th (Tfh). • An antigen specific lymphocyte clone develops with CSR and SHM. • This process continues about 3-6 weeks. Dr. Yildiran Siegrist, 2008, WHO

  16. With a Polisaccaride antigen No or weak Germinal response Dr. Yildiran Siegrist, 2008, WHO

  17. Antibody response to vaccine Continues for a several years Dr. Yildiran Siegrist, 2008, WHO

  18. T cell response to antigen Dr. Yildiran Siegrist, 2008, WHO

  19. T cell reponse to antigen • Vaccine antigen presented to both Th and CD8 by APC. • Th cell differentiated to Th1 (infection) and to Th2. • Th1 cells provides CD8 transforming to memory cells. But, Th2 cells inhibits. • Central (life long) and effector (short) CD8 memory cells come out. • If there is no danger signal, Treg cells come out. • This response couldn’t be provided by vaccine antigen. • HIV, HCV ve sıtma için çalışılıyor. Dr. Yildiran Siegrist, 2008, WHO

  20. Siegrist, 2008, WHO • Actual vaccines are produced as ampirically, it is not know how they affect totally. • For long protection, it must affect T cell for long protection. • However, vaccines could provide only short protection. • It is not known, vaccines long term effects on health. Dr. Yildiran

  21. Immunerepertoire • The immune repertoire, is defined as, the number of different sub-types an organism's immune system makes, of any of the 6 key types of protein, either immunoglobulin or T cell receptor. Dr. Yildiran

  22. Hygienhypothesis • This hypothesis states that a lack of early exposure to microorganisms (e.g flora, probiotics, parasites) increases susceptibility to allergic diseases Treg Th2 Th1 Texeira, 2002 Dr. Yildiran

  23. Brain immunity • Brain continues to developing postnatal for several years • There is no lymphatic system in brain. • The only immune system cell in is microglia (macrophage). It is important in neuroimmunological diseases. • Complement system could have an important role in neurocognitive disease like alzheimer. Dr. Yildiran Schlegelmilch, 2011

  24. Disadvantages of actual vaccines • Bypassing mucosal/innate immunity (Buonaguro, 2011) • Adjuvants also provides costimulus causing autoimmunity (Schwartz, 2003) • Imbalance of postnatal microbiota give rise to autoimmunity (Ygberg, 2012). • Mercury/aluminium are neurotoxic (Tomljenovic, 2011). Dr. Yildiran

  25. Contaminated vaccines • SV40 • Pirions Victoria, 2010 Dr. Yildiran

  26. Immune-senecense • By aging, cell numbers and immune and vaccine responses clearly decrease (Engelman, 2011). Dr. Yildiran

  27. PRİMUM NON NOCERA Dr. Yildiran

  28. Def-i mazarrat celb-i menafiden evladır. • Expelling the evil is more useful than calling benefit. Dr. Yildiran

  29. Immunization • Vaccination: to administer a vaccine • Immunization: to perform immunity • Passive immunization • İmmunoglobulin • Active immunization • Purpose: • To prevent epidemics • To prevent complications • The most powerful immunity is the natural immunity Abbas, Immunology Dr. Yildiran

  30. Infant deaths cdc.gov Dr. Yildiran

  31. Under fiveyearsInfantdeaths Dr. Yildiran Black, Lancet 2003

  32. Cause of deaths Dr. Yildiran Black, Lancet 2003

  33. Dr. Yildiran

  34. Dr. Yildiran

  35. Dr. Yildiran

  36. Dr. Yildiran

  37. AutoimmuneEpidemics • There are about 100 autoimmune diseases • What are the prevalences? Less known • After 1960, T1DM, asthma, MS, autism clearly increased. Dr. Yildiran

  38. Dr. Yildiran

  39. Mercurychangedto Al • To prevent contamination, mercury compound thimerosal included to vaccine. This could be related with autism. • This compound doesn’t used in vaccine for this cause. • Instead aluminium used, however it is also neurotoxic. Panja, 2005 Dr. Yildiran

  40. Collective vaccination principles 1. Collective vaccination programmes should target serious diseases that are a public health problem. 2. Each vaccine, and the programme, as a whole must be effective and safe. 3. The burdens and inconveniences for participants should be as small as possible. 4. The programme’s burden/benefits ratio should be favourable in comparison with alternative vaccination schemes or preventative options. 5. Collective vaccination programmes should involve a just distribution of benefits and burdens. 6. Participation should, generally, be voluntary unless compulsory vaccination is essential to prevent a concrete and serious harm. 7. Public trust in the vaccination programme should be honoured and protected. Verweij et al, Vaccine, 2004 Dr. Yildiran

  41. Informed Consent • The family should have been informed about mentioned disease and its vaccine. • Written informed consent should be taken Dr. Yildiran

  42. Vaccine types Dr. Yildiran

  43. Do not vaccinate • Anaphylactic reation (Absolute contrindication) • Sensitivity to vaccine material • mid-severe disease with fever or not • Patients that use Steroid (live vaccine) Sağ. Bak. Dr. Yildiran

  44. Dr. Yildiran

  45. Mandatory Immunization • Ethical? • It is only recommended in England, Baltic countries (Goulden, 2010) • Infant death rates are about half of USA (Miller, 2011). Dr. Yildiran

  46. Repot to Health Directorate • Abscess on injection site • BCG lymphadenitis • All deaths after vaccinations • Hospitalization need after vaccination • All cases that possible relationship with vaccination Katkı, 2006 Dr. Yildiran

  47. Hepatitis B • According to WHO: BW <2000 g, mother is transporter of Hep B or unknown, administer the first shot on the first 12 hours, then is repeated on the 1st, 2nd, 12th months (totally, 4 doses), furtherly HBIG is given. • No need to determine serological tests of hepatitis B in any age. Sağ. Bak. Dr. Yildiran

  48. BCG • Produced from M. bovis. • Effective in Miliary disease and meningitis. • Should be given into the skin, if not adverse events increase. • The most common adverse events are ulcration and lymphadenitis. • Could be cause widespread infection in persons that normal immunity (?). • Contrindicated in SCID. • Formerly, it was applied four doses. Katkı, 2006 Dr. Yildiran

  49. DaBT(Diphteria, Acellular pertussis, Tetanose) • Pathogen B. Pertussis, high mortality • İts toxin and phylamentous hemaglutininare important. • Adverse event ratio is more possible in whole killed vaccine. • It could cause sudden death abd encephalopathia. • If there is an encephalopaty or unrecovered convulsion in 24 hours, do not perform another dose. • Do not if there is progressive neurological disease. • Persistent crying (<3 h) is possible. Dr. Yildiran Katkı, 2006

  50. Diphteria C. Diftheriae its toxin causes membranes on pharynx • Antigenicity of vaccine is weak • Booster doses in ten years should be done. • Nodules on the injection site is possible because of aluminium ingredient. • Tetanos pathogen is C. Tetani produces tetanolysin and tetanospasmin. • Natural immunity doesn’t develop after infection. • After 7 years old age, vaccine is performed as DT. Dr. Yildiran

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