Come il sistema immunitario ci difende dalle infezioni

Come il sistema immunitario ci
difende dalle infezioni
Paola Parronchi
Convegno ‘Conoscere le Malattie Rare. Le Immunodeficienze’, Arezzo, 29 Novembre 2008
The story comes from far
1908
Nobel Prize
Paul Ehrlich
Magic bullets
ra
Pha
g
cytsurvive
Struggle oto
es
e
is
nt
A
Ilya Mechnikov
‘….There is no need to be a doctor or a
scientist to wonder why the human body
is capable of resisting so many harmful
agents in the course of everyday life. It
is often seen that in households where
all members are exposed to the same
danger, or again in schools or troops
where everyone lives the same life,
disease does not strike everyone
indifferently. For some individuals who
go down at the attack, there are others
who have immunity to a greater or lesser
extent….’
Cells of the
immune system
are widely
distributed
Thymus
Lymph node
Hassal’s body
Spleen
MALT
GALT
N
at
ur
al
Ar
tif
i
cia
l
Active
Passive
Natural vs artificial, active vs passive immunity
The three levels for immune defense
Innate
immunity
Natural
barriers
Specific
immunity
Physical and chemical barriers
Tears
Skin and mucosal
integrity
Sweat
Saliva
Urine
Stomach
acid
The ‘ordinary’ view of innate immunity
• Invariant (aspecific)
• Rapid (minutes to hours)
• Generalized
The ‘ordinary’ view of innate immunity
• Invariant (aspecific)
• Rapid (minutes to hours)
• Generalized
worms
bacteria
viruses
fungi
They share common recognition patterns
(Pathogen-Associated Molecular Patterns-PAMPs)
recognized by
specific Pattern Recognition Receptors-PRRs
Innate microbial sensors are express
by different cell types
Pentraxins
TLR
Liu AH JACI 2008
Ligands for TLRs are expressed by pathogens
Nat Rev Microbiol 2007
The two arms of innate immunity
Cells
Soluble factors
Complement
Interferons
Acute phase proteins
The complement system
The complement system
Interferons (α, β, λ, ω) in the mechanisms
of innate immunity
Effects of IFNs
Interferon deficiencies
The two arms of innate immunity
Cells
Granulocytes
Monocytes/
macrophages
Mast cells
NK cells
Soluble factors
Innate immunity in the war against
pathogens Neutrophils (1h-3d)
Macrophages (8h-mo)
increase capillary permeability Remove cellular debris and
pathogens
Stimulate repair
Activate specific immunity
Phagocytosis and diapedesis are main
features of innate cells
Circulating monocyte
eating malaria parasite
Neutrophil
attacking bacteria
Macrophages and dendritic cells:
a bridge between innate and adaptive
immunity
The phagocyte
‘eats’ a bacteria
The antigen is digested
and reaches the surface
The antigen is
The
recognized
immunological
by a T cell
synapsis
The dogma of Antigen processing
and association with MHC
The T cell
activates
Adaptive immunity:
knocking down pathogens
Immunocompetent cells
- T cells
- B cells
Soluble factors (cytokines)
The humoral branch of immunity
Ig levels depend on age
Ab
Ag
Age
IgG
IgA
IgM
0-14 days
6.0-16.0
0.01-.1
0.1-0.6
2-6 weeks
2.0-6.0
0.01-0.5
0.2-0.8
7 weeks6months
2.0-7.0
0.01-0.8
0.2-1.0
7-24 months
3.0-10.5
0.1-1.2
0.3-1.5
2-5 years
4.5-11.5
0.3-1.6
0.5-1.9
6-10 years
6.0-13.0
0.4-2.2
0.5-2.1
11-16 years
6.0-15.0
0.7-2.3
0.5-2.2
Adult
7.0-16.0
0.8-4.0
0.4-2.5
>70 years
6.0-15.0
0.8-4.0
0.4-2.4
Antibodies: not just neutralization
CD4+ T cells orchestrate adaptive
immune response
CD4
CD4
CD20
CD8
CD4
CD20
CD8
CD20
CD8
CD20
TheT cell
‘portfolio’
Help
cytotoxic responses
Help
antibody production
T-B interaction is essential
for antibody production
CD27
CD4
CD20
CD138
Newly identified molecules and receptors
explain subsets of ICV
BAFF
APRIL
B cell
Università di Firenze
DENOthe
Azienda OspedalieroUniversitaria Careggi
DAI Biomedicina
Sezione di Immunoallergologia
S.O.D.
(Dir. Prof. Enrico Maggi)
Immunoallergologia
(Dir. Prof. Enrico Maggi)
Immunologia e Terapie Cellulari
(Dir. Prof. Sergio Romagnani)