receptors and cell-surface molecules of macrophages tlr4 + cd14 mhci mhcii tlr – pattern...
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RECEPTORS AND CELL-SURFACE MOLECULES OF MACROPHAGES
TLR4 + CD14
MHCI
MHCII
TLR – pattern recognition Rs
CR1 (CD35)
CR3 (CD11b/CD18)
LFA1 (CD11a/CD18)
FcRIII (CD16)
FcRII (CD32)
FcRI (CD64)
Ag + IgG complex
Mannose receptor
Scavenger receptor
Mϕ
!!
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
!
napok
vírus-titer
2 4 6 8 101 3 5 7 9 1211 13
KINETICS OF VARIOUS ANTI-VIRAL MECHANISMS
Complement
AntibodyCytotoxic T cellsNK cells
IFNα/β, IL-12
days
lev
el/a
cti
vity
VIRUS TITER
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 re-infected, but some elderly got sick
1. Life long protection against some viruses exists
2. Maintenance of memory does not require the sustained or intermitting presence of the virus
IMMUNOLOGICAL MEMORY
Inhabitants: 46 000Area: 1 400 km2
THE TWO ARMS OF THE IMMUNE SYSTEM
Differentiation between harmless and harmful impactsDETECTION OF STRESS AND DANGER SIGNALSINNATE IMMUNITY
Differentiation between self and non-self structuresAntigen-specific recognitionADAPTIVE IMMUNITY
Neutralization and elimination of foreign and harmful structuresEXECUTIVE FUNCTIONSCOORDINATED AND REGULATED ACTIONS
INNATE IMMUNITY
- immediate reaction- not antigen-specific- no memory
ADAPTIVE IMMUNITY
- developes in several days- specific
- has memory
Humoral immunityCellular immunity
communication
!!
B cell memory:
Quicker responseIncrease in the number of specific B cellsThe amounts of antibody are bigerHigher affinity antibodies (‘more specific’)Isotype switch
In case of T dependent B cell activation
!!
Antigen
AActivation of ctivation of specific B cellsspecific B cells
1. 1. Clonal Clonal expansionexpansion
Antigen Antigen
2.Differentiation
Plasma cells, antibody production
MEMORY B CELLS
Antigen
!
Antigen
Antigen recognition by specific BCR induces clonal expansion and differentiation of the sepcific B cells.
Memory B cells
proliferation and differentiation to plasma cell upon re-activation or entry to the GC reaction again
and
Long-lived plasma cellsPlasma cells generated during GC reaction migrate to bone marrow andsurvive for years, producing antibody Much of circulating IgG is produced by long-lived plasma cells, provides initial protection
B cell memory is provided by:
Ig . C onc entra tion
na p o k
p rim er response
„A” a ntig né
IgM
IgGIgAIgE
Szekund er ’la syec ond a ry response
„A” és a ntig én
„B”
5 10 15 20 25 30
IgM
primary response against B antigen
!
days
Repeated immunization
IgG
IgM
IgA
A F T E R B IR T H
breas t milkIgA
0
1 0 0 %( a d u l t )
3 3y e a r
2 546 a d u l t9 1m o n t h
maternal IgG
B E F O R E B IR T H
PRODUCTION OF IMMUNOGLOBULINS
IMMUNOLOGICAL MEMORY – B CELLSIMMUNOLOGICAL MEMORY – B CELLSSUMMARYSUMMARY
Memory B cells• 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
Plasma cellsProvides serological memory by pre-existing neutralizing Abs to pathogens and/or toxins
Germinal Center reaction• B cell proliferation• Somatic hypermutation• Affinity maturation
BT
BB
BBBB
BBB
B
BB
B
FDC
FDCFDC T
B
B
plasmacell
B – T cell collaboration
DEVELOPMENT OF CELLULAR MEMORYNegative regulation of the immune system
Days5 10 15 20 25 30
Naive lymphocytes
Az antigen-specific cell number
Primary effector cells
Secondary effector T
cells
Memory
DIFFERENTIATION
AICD
EXPANSION
AICD
MEMORY
Days
Activation Induced Cell Death
Effector T
Citokines/Cytotoxicity
AICD
Naive T
Central memory T
Effector T
Citokines/cytotoxicity
PERIPHERAL LYMPHOID ORGANS
PERIPHERAL TISSUESSkin dermis, gut lamina propria, alveolar space
Tissue-specific migration
Effector memory T
Effector T
Cytokines/cytotoxicity
ANTIGEN/SITE OF INFECTION
IMMUNOLOGICAL MEMORY MEDIATED BY T LYMPHOCYTES
Naive T cell Effector T cell
cytokine productioncytotoxicity
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
EffectorMemory 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
Maintained by cytokines:IL-7, IL-15
2X107
2X105
Proliferation
cytotoxicity
Functional differences between lymphoid tcm cells and tissue-resident TEM cells
Woodland DL & Kohlmeier JR 2009 Nat Rev 9:153killing
Active: generates memory response
Passive: ensure the protection by premade antibodies(the adaptive immune system of the person is not activated)
PROTECTED SUBJECT
serum antibody
PASSZÍV IMMUNIZÁLÁS
This is a case of PASSIVE IMMUNIZATION
Immune system is not activatedprompt effect
temporary protection/effect
Immunoglobulin degradation
Human immunoglobulin transgenic mouse
immunization mouse monoclonal antibodies
ENDANGERED SUBJECT
immunization
human monoclonal antibodies
humanized mouse monoclonal antibodies
Active and passive immunization
active passive
protection slow immediate(2 weeks)
Time-span long short(years)
time
activepassive
injection
protection
!!
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
!
IgG
IgM
IgA
A F T E R B IR T H
breas t milkIgA
0
1 0 0 %( a d u l t )
3 3y e a r
2 546 a d u l t9 1m o n t h
maternal IgG
B E F O R E B IR T H
PRODUCTION OF IMMUNOGLOBULINS
Pathological consequences of placental Pathological consequences of placental transport of IgGtransport of IgG
(hemolytic disease of the newborn)(hemolytic disease of the newborn)
Passive anti-D IgG
anti-RhIgM
Immunization
Active PassiveHost itself produce preformed antibodies
antibodies and cells are imported to the host
biotic bioticartificial artificial