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Transcript
RECEPTORS AND CELL-SURFACE MOLECULES OF
MACROPHAGES
TLR4 + CD14
Scavenger receptor
Mannose receptor
MHCI
TLR – pattern
recognition Rs
FcRI (CD64)
Ag + IgG
complex
FcRII (CD32)
FcRIII (CD16)
LFA1 (CD11a/CD18)
MHCII
Mϕ
CR1 (CD35)
CR3 (CD11b/CD18)
!
!
!
Anti-viral immune response Type I INTERFERONs
vírus
IFN és IFN
!
!
Anti-viral immune response
Defense:
Innate Immunity:
– type I interferons(INFα, β)
– NK cells
Adaptive immunity
B cells – antibody-mediated neutralization
T cells --- cytotoxic T cells, cytokines
KINETICS OF VARIOUS ANTI-VIRAL MECHANISMS
IFNα/β, IL-12
Cytotoxic T cells
Antibody
level/activity
NK cells
Complement
vírustiter
VIRUS TITER
1
2
3
4
5
6
7
8
9
10 11 12
13
na pok
days
IMMUNOLOGICAL MEMORY
Inhabitants: 46 000
Area: 1 400 km2
1781:
Measles epidemics in the Faroe islands
after the epidemics the island has remained measles free for 65 years
1846:
Another epidemics
Those, who were elder than 65 years and were sick in 1781 were not
some elderly got sick
re-infected, but
1. Life long protection against some viruses exists
2. Maintenance of memory does not require the sustained or intermitting
presence of the virus
THE TWO ARMS OF THE IMMUNE SYSTEM
Differentiation between harmless and harmful impacts
DETECTION OF STRESS AND DANGER SIGNALS
INNATE IMMUNITY
Differentiation between self and non-self structures
Antigen-specific recognition
ADAPTIVE IMMUNITY
Neutralization and elimination of foreign and harmful structures
EXECUTIVE FUNCTIONS
COORDINATED AND REGULATED ACTIONS
INNATE IMMUNITY
- immediate reaction
- not antigen-specific
- no memory
ADAPTIVE IMMUNITY
communication
- developes in several days
- specific
- has memory
Humoral immunity
Cellular immunity
!
!
!
B cell memory:
Quicker response
Increase in the number of specific B cells
The amounts of antibody are biger
Higher affinity antibodies (‘more specific’)
Isotype switch
In case of T dependent B cell activation
!
Antigen recognition by specific BCR induces clonal
expansion and differentiation of the sepcific B cells.
Plasma
cells,
antibody
production
A n ti g e n
2.Differen
tiation
Activation of
specific B cells
1. Clonal
expansion
A n ti g e n
MEMORY B CELLS
A n ti g e n
!
A n ti g e n
A n ti g e n
B cell memory is provided by:
Memory B cells
proliferation and differentiation to
the GC reaction again
plasma cell upon re-activation or entry to
and
Long-lived plasma cells
Plasma cells generated during GC reaction migrate to bone marrow and
survive for years, producing antibody Much of circulating IgG is produced by
long-lived plasma cells, provides initial protection
!
Ig. Concentration
Repeated immunization
Szekunder ’lasyecondary resp
IgG
IgA
IgE
primer response
IgM
IgM
primary
response
against B
antigen
5
„A” antig é n
10
15
20
25
„A” és „B”
antigén
30
napok
days
!
NEUTRALIZATION
PRODUCTION OF IMMUNOGLOBULINS
BEFORE BIRTH
AFTER BIRTH
breast milk
IgA
100%
(adult)
maternal IgG
IgM
IgG
IgA
0
3
month
6
9
1 2 3 4 5 adult
year
IMMUNOLOGICAL MEMORY – B CELLS
SUMMARY
Germinal Center reaction
• B cell proliferation
• Somatic hypermutation
• Affinity maturation
Memory B cells
B
B
FDC
B
FDC
B
• Perviously activated
• Passed through affinity maturation
• Present in the circulation
• proliferation and differentiation to
plasma cell upon re-activation or entry to
the GC reaction again
T
B
B
B BB B
BB B B B
T
B
plasma
cell
B – T cell
collaboration
Plasma cells
Provides serological memory by
pre-existing neutralizing Abs to
pathogens and/or toxins
T-CELL MEMORY
Central memory cells
Effector memory cells
!
T cell memory:
Quicker response
Increase in the number of responding cells
!
DEVELOPMENT OF CELLULAR MEMORY
Negative regulation of the immune system
AICD
Activation Induced Cell
Death
DIFFERENTIATION
Naive
lymphocytes
Memory
Az antigen-specific cell
number
Secondary
effector T
cells
Primary
effector cells
EXPANSION
AICD
MEMORY
5
10
15
20
25
30
Days
Days
Effector T
Naive
T
AICD
Citokines/Cytotoxicity
Central memory
T
PERIPHERAL
LYMPHOID
ORGANS
Effector memory
T
PERIPHERAL TISSUES
Skin dermis, gut lamina
propria, alveolar space
Tissue-specific migration
Effector T
Effector T
Cytokines/cytotoxicity
Citokines/cytotoxicity
ANTIGEN/SITE OF
INFECTION
IMMUNOLOGICAL MEMORY MEDIATED BY T LYMPHOCY
Naive T cell
Effector T cell
cytokine production
cytotoxicity
Central
Memory T cell
Effector T cell
• Previously activated, partially differentiated cell type
• Circulating CCR7+ cells in blood, lymphoid tissues
• High proliferation rate induced by activation signals
• Rapid differentiation to effector cells
Effector
Memory T cell
Effector T cell
• Previously activated, partially differentiated cell type
• Closest to the effector state
• Circulating CCR7- cells in blood and tissues
• Slow proliferation, rapid effector functions
2X107
Maintained by cytokines:
IL-7, IL-15
2X105
Functional differences between lymphoid tcm
cells and tissue-resident TEM cells
Proliferation
cytotoxicity
killing
Woodland DL & Kohlmeier JR 2009 Nat Rev 9:153
AGE
THYMUS
PERIPHERY
M
E
N
M
A
O
I
R
V
Y
E
IMMUNOLOGICAL EXPERIENCE
A TERMÉSZETES ÉS SZERZETT IMMUNITÁS EGYÜTTMŰKÖDÉSE
IDŐBEN
Active and passive immunization
Active: generates memory response
Passive: ensure the protection by premade antibodies
(the adaptive immune system of the person is not activated)
!
!
PASSZÍV IMMUNIZÁLÁS
mouse monoclonal
antibodies
immunization
humanized mouse monoclonal
antibodies
immunization
PROTECTED
SUBJECT
serum antibody
ENDANGERED
SUBJECT
Human immunoglobulin
transgenic mouse
human monoclonal
antibodies
This is a case of PASSIVE
IMMUNIZATION
Immune system is not activated
prompt effect
temporary protection/effect
Immunoglobulin degradation
Active and passive immunization
protection
Time-span
active
passive
slow
(2 weeks)
long
(years)
immediate
protection
passive
active
injection
time
short
!!
!
Anti-viral immune response
Defense:
Innate Immunity:
– type I interferons(INFα, β)
– NK cells
Adaptive immunity
B cells – antibody-mediated neutralization
T cells --- cytotoxic T cells, cytokines
PRODUCTION OF IMMUNOGLOBULINS
BEFORE BIRTH
AFTER BIRTH
breast milk
IgA
100%
(adult)
maternal IgG
IgM
IgG
IgA
0
3
month
6
9
1 2 3 4 5 adult
year
Pathological consequences of placental
transport of IgG
(hemolytic disease of the newborn)
anti-Rh
IgM
Passive anti-D IgG
Immunization
Active
Host itself produce
antibodies and cells
biotic
artificial
Passive
preformed antibodies
are imported to the host
biotic
artificial
Immunitás
Természetes
Aktív:
betegség,
immunizálódás
(sorozatos találkozás az adott
kórokozóval)
Passzív
- in utero, placentán át, maternális
(anyai IgG, folyamatos, homológ)
- születés után, colostrális, anyatej
útján IgG, IgA