VACCINAZIONI QUALI SONO I SOGGETTI A RISCHIO? IL PUNTO DI VISTA DEL SISTEMA IMMUNITARIO

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1 VACCINAZIONI QUALI SONO I SOGGETTI A RISCHIO? IL PUNTO DI VISTA DEL SISTEMA IMMUNITARIO Rita Carsetti OpBG Unità di Immunologia Unità di diagnostica Immunologica

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3 IMMUNOLOGICAL MEMORY IS THE PROPERTY OF THE IMMUNE SYSTEM OF RECOGNIZING AND NEUTRALIZING A PREVIOUSLY ENCOUNTERED PATHOGEN THEREBY PREVENTING INFECTION AND DISEASE Memory B cells IgM memory Switched memory antibodies Long-lived plasma cells

4 RISPOSTA T- DIPENDENTE protein antigens day 3 day 7 day 14 Memory B cells plasma cells extra-follicolar phase germinal center reaction

5 PERIPHERY prima ry booster BM

6 RISPOSTA T- INDIPENDENTE Polysaccharide antigens Extrafollicular response Non genera memoria

7 PERIPHERY prima ry booster BM

8 proteine carboidrati RISPOSTA T- DIPENDENTE RISPOSTA T- INDIPENDENTE T IgG IgM

9 ANTIGENE GLICOCONIUGATO TRASFORMA UN T ANTIGENE T-INDIPENDENTE IN T-DIPENDENTE IgG

10 LACK OF IgM MEMORY: SPLENECTOMY/ASPLENIA Eur J Immunol Oct;43(10): doi: /eji

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12 cord blood Mem tot Mature Transitional tr ma adult tr CD me <1anno 2anni 5anni 8anni 10anni

13 Kruetzmann et al., J Exp Med 2004

14 LACK OF IgM MEMORY B CELLS IN ASPLENIC AND SPLENECTOMIZE PATIENTS

15 Children 21 splenectomized 19 controls Adults 57 splenectomized 47 controls spherocytosi s trauma thalassemia spherocytosis trauma non-haemat. neoplasia other

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18 ADULTS

19 CHILDREN

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21 Le IgM memory sono molto poche nei pazienti splenectomizzati. Per questo le risposte T-indipendenti sono assenti. In questi casi però si possono indurre le cellule B MATURE A fare anticorpi somministrando i vaccini coniugati, dopo la splenectomia T IgG

22 LACK OF ANTIBODIES: RESPONSE TO HBV VACCINES Eur J Immunol Jun;41(6): doi: /eji Epub 2011 May 25.

23 HEPATITIS B: COMPARISON BETWEEN TWO VACCINES THAT INDUCE DIFFERENT LEVELS OF ANTIBODIES Infanrix-Hexa VAC A: 710 pts 34 pts Hexavac VAC B (831 pts) 65 pts VACCINEES: LARGE GROUP 710 Infanrix, 831 Hexavac SMALL GROUP 34 Infanrix, 65 Hexavac

24 SERUM ANTIBODIES AGAINST HBsAG ARE LOWER IN THE HEXAVAC GROUP: VANING IMMUNITY?

25 BOTH GROUPS OF CHILDREN RESPOND EQUALLY WELL TO A BOOSTER DOSE OF HBV VACCINE

26 5 years after vaccination THE MEMORY POOL OF VAC A AND VAC B GROUPS IS EQUALLY EFFICIENT IN GENERATING PLASMA CELLS UPON CpG STIMULATION

27 5 years after vaccination THE FREQUENCY OF ANTI-HBsAg MEMORY B CELLS IS NOT DIFFERENT IN VAC A AND VAC B GROUPS

28 5 years after vaccination THE FREQUENCY OF ANTI-HBsAg MEMORY B CELLS IS NOT DIFFERENT IN VAC A AND VAC B GROUPS

29 5 years after vaccination THE FREQUENCY OF ANTI-HBsAG MEMORY B CELLS IS NOT CORRELATED TO THE CONCENTRATION OF SERUM ANTIBODIES

30 AFTER BOOST VAC A AND VAC B GROUPS RESPOND EQUALLY WELL TO BOOST

31 AFTER BOOST THE FREQUENCY OF ANTI-HBsAg MEMORY B CELLS SIGNIFICANTLY INCREASES AFTER BOOST

32 AFTER BOOST SPECIFIC MEMORY B CELLS ARE FUNCTIONAL IN CHILDREN WITH LOW LEVELS OF SPECIFIC SERUM ANTIBODIES Spots/106 cells pre post Memory anti-hbsag pre post Serum anti-hbsag IgG Anti-HBsAg (mu/ml)

33 CONCLUSIONS: 1- Switched memory B cells maintain specific memory independently of serum antibodies 2.-Memory B cells and long-lived plasma cells are independently generated 3.-The ability to generate short-lived plasma cells differs among individuals

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35 REDUCTION OF SWITCHED MEMORY B CELLS: DOWN SYNDROME

36 Down Syndrome is associated to an increased frequency of infection, autoimmunit and leukemia. Immunodeficiency is an integral part of the syndrome In preparation

37 CLP CD4 CD8 70% CD4 memory CD8 memory

38 50% 50% 30% 14%

39 Controlli pre Controlli post IgA IgM IgG totali Down pre Down post IgA IgM IgG totali

40 700 pneumo flu controls IgA Pneumo IgM IgG flu IgA IgM IgG 700 pneumo flu Down IgA Pneumo IgM IgG flu IgA IgM IgG

41 IMMUNOLOGICAL MEMORY IS THE PROPERTY OF THE IMMUNE SYSTEM OF RECOGNIZING AND NEUTRALIZING A PREVIOUSLY ENCOUNTERED PATHOGEN THEREBY PREVENTING INFECTION AND DISEASE Memory B cells IgM memory Switched memory antibodies Long-lived plasma cells

42 Manuela Rosado Marco Scarsella Simona Cascioli Ezio Giorda Federica Capolunghi Alaitz Aranburu Valentina Marcellini OpBG Alberto Ugazio Alberto Tozzi Franco Locatelli Luciana Nicolosi Alberto Villani Diletta Valentini S.Matteo, PV Antonio Disabatino Gino Corazza Area di Immunologia GRAZIE

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