Immunogenicita’ ed efficacia
della vaccinazione anti‐
pneumococcica
Sabato 25 ottobre 2014
Rita Carsetti, Ospedale Pediatrico Bambino Gesù
minutes
hours
days
minutes
memory T
memory B
hours
plasma cell
days
RISPOSTA T- DIPENDENTE
protein antigens
day 3
day 7
day 14
Memory B cells
plasma cells
extra-follicolar
phase
germinal center reaction
PERIPHERY
primary
BM
booster
RISPOSTA T- INDIPENDENTE
Polysaccharide antigens
Extrafollicular response
Non genera memoria
PERIPHERY
primary
BM
booster
The increased susceptibility to mucosal infection in infancy is due to the
lack of memory B cells.
proteine
RISPOSTA T- DIPENDENTE
carboidrati
RISPOSTA T- INDIPENDENTE
T
IgG
IgM
ANTIGENE GLICOCONIUGATO
TRASFORMA UN T
ANTIGENE
T‐INDIPENDENTE
IN T‐DIPENDENTE
IgG
The increased susceptibility to infection of splenectomized individuals is due to the lack of memory B cells
Kruetzmann et al., J Exp Med 2004 Children
21 splenectomized
19 controls
Adults
57 splenectomized
47 controls
thalassemia
spherocytosis
spherocytosis
trauma
trauma
congenital
non-haemat. neoplasia
other
Normal anti‐pneumococcal antibody levels in splenectomized individuals
ADULTS
CHILDREN
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
Down Syndrome is associated to an increased frequency
of infection, autoimmunity and leukemia.
Immunodeficiency is an integral part of the syndrome
Elderly patients an increased risk of pneumococcal infection.
Why?
Do they lose memory B cells?
CLP
CD4
CD8
70%
CD4 memory
CD8 memory
50%
50%
30%
14%
12000
10000
8000
6000
Controlli pre
Controlli post
4000
2000
0
IgA
IgM
IgG
totali
12000
10000
8000
6000
Down pre
Down post
4000
2000
0
IgA
IgM
totali
IgG
pneumo
flu
700
600
500
400
controls
300
200
100
0
Pneumo
IgA
IgM
IgG
flu
IgA
IgG
flu
pneumo
700
IgM
600
500
400
Down
300
200
100
0
Pneumo
IgA
IgM
IgG
flu
IgA
IgM
IgG
IMMUNOLOGICAL MEMORY IS THE PROPERTY OF THE IMMUNE SYSTEM
OF RECOGNIZING AND NEUTRALIZING A PREVIOUSLY ENCOUNTERED PATHOGEN
THEREBY PREVENTING INFECTION AND DISEASE
IgM memory
Memory B cells
Switched memory
antibodies
Long‐lived plasma cells
Each vaccination leaves a permanent imprint in the immune system, embodied by
memory B cells, long lived plasma cells and their antibodies.
…but do vaccinations influence other cells of the immune system?
We have studied the immune system of 70 children before and after influenza vaccination
Pre
(median, range)
Post
(median, range)
p value
B cells (% of lymphocytes)
23.5 (9.7‐49.6)
19.6 (11.6‐44.9)
0.128
Memory B cells (% of B cells)
12.8 (3.4‐25.5)
12.6 (4.3‐26.9)
0.805
Mature B cells (% of B cells)
44.2 (31.9‐59.1)
46.6 (29.5‐55)
0.603
Transitional B cells (% of B cells)
9.9 (1.6‐29.8)
9.8 (3.2‐31.6)
0.568
IgM memory B cells (% of B cells)
6.7 (1.8‐15.2)
5.6 (2.2‐13.5)
0.045
Switched memory B cells (% of B cells)
6.7 (1.4‐18.7)
6.6 (2.4‐20.4)
0.381
NK cellsa (% of lymphocytes)
3.8 (1.1‐13.8)
4.15 (1.3‐16.3)
0.08
NKT cellsb (% of lymphocytes)
1.3 (0.4‐10)
3.15 (0.5‐9)
0.09
T cells (% of lymphocytes)
67.2 (41.5‐83.4)
69.5 (45.6‐82.5)
0.099
CD4 T cells (% of CD3pos cells)
59.7 (42.7‐72.3)
58.25 (35.5‐74.7)
0.163
CD8 T cells (% of CD3pos cells)
30.7 (17.9‐44.1)
30.95 (19‐54.4)
0.382
IgG anti‐Vaxigrip AFCsc (spots/106 cells)
50.3(0‐2142)
112.6 (0‐1661)
0.001
IgG anti‐Texas AFCsc (spots/106 cells)
45.0(0‐2742)
62.5 (0‐485)
0.344
60 (0‐960)
335 (10‐3579)
<0.001
203.5 (0‐601)
463 (0‐640)
?
IgM anti‐Vaxigrip ASCsa (spots/106 cells)
IgM anti‐Texas ASCsc (spots/106 cells)
In children influenza vaccination does not have any measurable effect
On the frequency and distribution of B, T, NK and NK T cells. Further studies
1. Down syndrome
2. Elderly individuals
3. HPV girls and boys
Manuela Rosado
Marco Scarsella
Simona Cascioli
Ezio Giorda
Federica Capolunghi
Alaitz Aranburu
Valentina Marcellini
Eva Piano Mortari
OpBG
Alberto Ugazio
Alberto Tozzi
Franco Locatelli
Luciana Nicolosi
Alberto Villani
Diletta Valentini
S.Matteo, PV
Antonio Disabatino
Gino Corazza
GRAZIE
Area di Immunologia