chapter 11. immune response (1) i. introduction ii. antibody-mediated humoral immunity
TRANSCRIPT
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Chapter 11. Immune response (1)Chapter 11. Immune response (1)
I. IntroductionI. Introduction
II. Antibody-mediated Humoral II. Antibody-mediated Humoral ImmunityImmunity
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I. IntroductionI. Introduction
1. Concept of Immune Response1. Concept of Immune Response
2. Types of Immune Response2. Types of Immune Response
3. Process of Immune Response3. Process of Immune Response
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1. Immune response
The immune system of body is able to The immune system of body is able to recognize subtle chemical differences that recognize subtle chemical differences that distinguish one foreign pathogen from another. At distinguish one foreign pathogen from another. At the same time, the system is able to discriminate the same time, the system is able to discriminate between foreign molecules and the body’s own between foreign molecules and the body’s own cells and proteins. Once a foreign organism is cells and proteins. Once a foreign organism is recognized, the immune system eliminate or recognized, the immune system eliminate or neutralize the organism, finally.neutralize the organism, finally.
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2. Types of Immune Response2. Types of Immune Response
AutoimmunityAutoimmunity
selection Immune “Self”Ag Autoimmune Tolerance selection Immune “Self”Ag Autoimmune ToleranceAg system:Ag system: activation “non-self”Ag HI / CMI activation “non-self”Ag HI / CMI Immune Tolerance Immune Tolerance Hypersensitivity Reaction Hypersensitivity Reaction
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II. Antibody-mediated Humoral ImmunityII. Antibody-mediated Humoral Immunity
concept of HI concept of HI ,, simple process of HIsimple process of HI
1. Common rule of Ab production 1. Common rule of Ab production
2. Interaction between immune cells in2. Interaction between immune cells in
process of producing Ab process of producing Ab
3. Immune Memory 3. Immune Memory
4. Effect of Humoral Immunity 4. Effect of Humoral Immunity
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Humoral ImmunityHumoral Immunity ,, HIHI
Humoral immunity is mediated by antiHumoral immunity is mediated by antibodies of various different classes; which Abodies of various different classes; which Ab are produced by cells of the B cell lineage b are produced by cells of the B cell lineage in response to stimulation by Ag.in response to stimulation by Ag.
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Simple process of HI:
11 、、 TD—Ag APC TH BL2TD—Ag APC TH BL2
THmTHm BLmBLm
22 、、 TI—Ag BL1 Mature B cellTI—Ag BL1 Mature B cell
Plasma cellsPlasma cells
Ab Ab HIHI
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1.Common rule of Ab production
a. The regularity of Ig production in phylogenic ea. The regularity of Ig production in phylogenic evolution and development,and ontogenesis.volution and development,and ontogenesis.
b. The regularity of Ab production in the primary b. The regularity of Ab production in the primary and secondary responseand secondary response 。。
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Secondary Immune Response
When the immunized individual after a primary contact with antigen is injected by a second injection of the same antigen, production of antibody becomes apparent, this response is called the secondary response.
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Primary IR Secondary IR
Antigen The first contact of an A second injection of the individual with an Ag same Aglatent period long (1W , 2-3W) short (1-3day) slow of Ab productionAb Conc. low in serum high in serum Maintain Time short,decrease quickly longertype of Ig IgM IgGAffinity lower higherpresent of Ag M, DC B cell
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Concentration of IgConcentration of Ig
IgIgMIgG
10day 3day
Latent period
Primary stimulation of AgPrimary stimulation of Ag Secondary stimulation of AgSecondary stimulation of Ag
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2. Interaction between immune cells2. Interaction between immune cells in the process of producing Ab in the process of producing Ab
TD—Ag responseTD—Ag responsea. Interaction between Ma. Interaction between M and Th cells and Th cells
* M* M presented Ag *Interaction between cells presented Ag *Interaction between cells
b. Interaction between Th cell and B cellsb. Interaction between Th cell and B cells
* B cell presented Ag * Interaction between* B cell presented Ag * Interaction between cellscells
c. Interaction between Mc. Interaction between M and B cells and B cells
TI—Ag responseTI—Ag response
B cell : response of TI—AgB cell : response of TI—Ag
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• Ags are ingested, processed, presented Ags are ingested, processed, presented by M by M (primary response)(primary response)
IngestionIngestion :: endocytosis, passive adhesionendocytosis, passive adhesion 。。 ProcessingProcessing :: lysosomal enzymes condense anlysosomal enzymes condense an
d degrade d degrade Ag,Ag,and combine to self-MHCII moland combine to self-MHCII molecules.ecules.
PresentationPresentation :: These complexes of peptide aThese complexes of peptide and MHC molecules are transported to the surnd MHC molecules are transported to the surface of the cell where they are recognized by tface of the cell where they are recognized by the T-cell receptor. he T-cell receptor.
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Exogenous AgExogenous Ag
endosome
Transportation
combination
degradation
expression
endocytosis
APC
CD4
TCRTCR
MHCII
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transcription
DNA
mRNA
Virus ( endogenous Ag )
translationPr
degradation CD8CTL
MHCI
Target cell
TCR
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• Interaction between MInteraction between M and Th cells and Th cells (( primary responseprimary response )) Double signal hypothesis of Th cell activation Double signal hypothesis of Th cell activation ::The first signal The first signal :: Th: TCR/CD3——APC: Ag-MHCII complexes Th: TCR/CD3——APC: Ag-MHCII complexes
at the same time, TH: CD4——APC: The at the same time, TH: CD4——APC: The 2,2,2 domain of MHCII2 domain of MHCII
The second signal The second signal :: APC: B7/BB1APC: B7/BB1 (( CMCM )——)—— TH: CD28TH: CD28 (( CMRCMR ))
TH secreted IL-2 and expressed IL-2RTH secreted IL-2 and expressed IL-2R
Finally cells divide, clones proliferation, and produce a kind of CK.Finally cells divide, clones proliferation, and produce a kind of CK.
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ICAM-1 LFA-1
APC(CMs)
MHC-IIAg
B7/BB1
VLA-4VCAM-1
CD2CD58
Cell activation,( CK )cell differentiation and clone proliferation
TH(CMRs)
TCR
CD3
CD4
CD28CTLA4
Signal 1
Signal 2
IL-2
IL-2R
Interaction between APC and Th cellInteraction between APC and Th cell
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MHC-Ag
APC
TCR/CD3
B7/BB1
CD28
TH
Signal 1 Signal 2
IL-2 production clone proliferation
APC
TH
Signal 1 Signal 2
not IL-2 production clone anergy
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inactivation
Suppressive immune response Suppressive immune response :: Hypersensitivity DiseaseHypersensitivity Disease Autoimmunity DiseaseAutoimmunity Disease Graft rejection responsesGraft rejection responses
Anti-B7AbCTLA4 IgAnti-CD28
Interdiction of co-stimulatory signals
THAPC MHC TCR
Ag
CD28
B7
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Enhancing immune responseEnhancing immune response :: Tumor immunity treatmentTumor immunity treatment
B7
Transfection B7gene
CTLMHC TCR
Ag
CD28
Tumor cellsignal1
signal2
CTLMHC TCR
Ag
CD28
Tumor cellsignal1
signal2
CTL activatedKiller tumor cell
CTL activatedKiller tumor cell
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• Interaction between Th and B cellsInteraction between Th and B cells (( secondary responsesecondary response ))
Th cell activationTh cell activation : : Double signal hypothesis Double signal hypothesis Signal 1Signal 1 :: Th: TCR/CD3——B cell: Ag-MHCII complexesTh: TCR/CD3——B cell: Ag-MHCII complexes
Th: CD4——B cell: Th: CD4——B cell: The The 2,2,2 domain of MHCII2 domain of MHCII
Signal 2Signal 2 :: Th: CD28 molecule ——B cell: B7 molecule.Th: CD28 molecule ——B cell: B7 molecule.
B cell activationB cell activation : : Double signal hypothesis Double signal hypothesis Signal 1Signal 1 :: B cell: BCR--AgB cell: BCR--Ag ,, IgIg,Ig,Ig transfer activation signal transfer activation signal 11
Signal 2 : B cell: CD40——Th: CD40LB cell: CD40——Th: CD40L
Th and B cell inducing signal of activation each otherTh and B cell inducing signal of activation each other ,, Th produced IL-4,5,Th produced IL-4,5,6.6.
B cell is helped at Th cell, finally B cell proliferated and differentiatedB cell is helped at Th cell, finally B cell proliferated and differentiated
turn into the plasma cells of producing a kink of Igs.turn into the plasma cells of producing a kink of Igs.
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CD3
singal
B cell activation
B cell
Ag
SIg
12
Signal 1
T cell
B7 CD28
ICAM-1 LFA-1
CD3
TCR
CD4
MHC-II
CD40LCD40
LFA-1 ICAM-1
Signal 2Signal 2
Th activationCK
Ag process
present
Interaction between B cell and T cellInteraction between B cell and T cell
CKR
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Ag
Bm
B B
B B
PC
IgM IgG
IgA IgE
Bm Bm
Bm Bm
Activate Th
Activate B
IL-2 , 4 , 5 , 6IL-1
process
present
process
present
proliferation
ingestion
ingestion
MHC-II
MHC-II
TCR
TCR
M M
differentiation
c. Interaction between M and B cells
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signalsignal
B cell B cell
I type: TI—Ag is
polyclonal stimulator II type: multiple repeat-lined antigenic determinant makes receptor linkage
TI-Ag response
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3. Immune Memory-Secondary response
CharacteristicCharacteristic : :
a. Immune memory cellsa. Immune memory cells
b. Class switching of Igb. Class switching of Ig
c. Affinity Maturation of Abc. Affinity Maturation of Ab
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CharacteristicCharacteristic :: * Immune memory cells: THm Bm
* Involved in Humoral immunity and
cell-mediated immunty.
* Ab conc. increases , class switching of Ab , and affinity maturation of Ab
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4. Effect of Humoral Immunity
Neutralization of AbNeutralization of Ab Opsonization of AbOpsonization of Ab Complement dependent cell-mediated cComplement dependent cell-mediated c
ytotoxicity,CDCytotoxicity,CDC Antibody dependent cell-mediated cytoAntibody dependent cell-mediated cyto
toxicity,ADCCtoxicity,ADCC Immune regulation of AbImmune regulation of Ab
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Opsonization of Ab
Bacteria Anti-bacteria Ab M
FcrR
Boost up lick up action
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Target cell
M , NK
Dissolution of target cell
IgG
Surface AgFcrR
Antibody-dependent cell-mediated cytotoxicity, ADCC
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Chapter12. Chapter12. Immune response (2)Immune response (2)
I. Introduction I. Introduction
II. CD4 T-mediated immunityII. CD4 T-mediated immunity
III.CD8 T-mediated immunityIII.CD8 T-mediated immunity
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I. Introduction
1. Concept, Simple process1. Concept, Simple process
2. Major functions of CMI2. Major functions of CMI
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Simple process:Simple process:
TD-Ag Immune system
secondary
TDTH
Tc
CK
Cytotocixity
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2. Major Functions of CMI
Delayed Type Hypersensitivity, DTHDelayed Type Hypersensitivity, DTH Intracellular Anti-infection Intracellular Anti-infection Anti-tumor Anti-tumor Transplantation rejection reactionTransplantation rejection reaction Graft Versus Host Reaction, GVHRGraft Versus Host Reaction, GVHR Autoimmunity diseasesAutoimmunity diseases
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II. CD4 T-mediated immunity
1. Activation of CD4 T cells1. Activation of CD4 T cells
2. Formation of DTH inflammation2. Formation of DTH inflammation * CK production * Function of M* CK production * Function of M
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• Activation of CD4 T cells
Double signal hypothesis of CD4 T cell activation Double signal hypothesis of CD4 T cell activation ::The first signal The first signal :: Th: TCR/CD3——APC: Ag-MHCII complexes Th: TCR/CD3——APC: Ag-MHCII complexes
at the same time, TH: CD4——APC: The at the same time, TH: CD4——APC: The 2,2,2 domain of MHCII2 domain of MHCII
The second signal The second signal :: APC: B7/BB1APC: B7/BB1 (( CMCM )——)—— TH: CD28TH: CD28 (( CMRCMR ))
TH secreted IL-2 and expressed IL-2RTH secreted IL-2 and expressed IL-2R
Finally cells divide, clones proliferation, and produce a kind of CK.Finally cells divide, clones proliferation, and produce a kind of CK.
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IL-2RIL-2R APC(CMs)
TH(CMRs)
CD28CTLA4 CD3
TCR
CD4ICAM-1 LFA-1
MHC-II Ag
B7/BB1
VLA-4VCAM-1
CD2CD58
Signal1
Signal 2
IL-2
IL-2R
Cell activation,( CK )cell differentiation and clone proliferation
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APC T
APC T
APC T
T
T
T
T
IL-2
IFNr
TNF
T
M
rest
M
activation
CK of DTH reaction
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III.CD8 T-mediated immunity
1. Activation ofCD8 T cells1. Activation ofCD8 T cells
2. Mechanisms of Tc killing 2. Mechanisms of Tc killing target cellstarget cells
a. a. PerforinPerforin
b. b. GranzymesGranzymes
c. c. TNF associated proteinsTNF associated proteins
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• Activation of CD8 T cells
Double signal hypothesis of CD8 T cell activation Double signal hypothesis of CD8 T cell activation ::The first signal The first signal :: Tc: TCR/CD3——Target cell: Ag-MHC-I complexes Tc: TCR/CD3——Target cell: Ag-MHC-I complexes
at the same time, Tc: CD4——Target cell: The at the same time, Tc: CD4——Target cell: The 3 domain of MHC-I3 domain of MHC-I
The second signal The second signal :: Target cell: B7/BB1Target cell: B7/BB1 (( CMCM )——)—— Tc: CD28Tc: CD28 (( CMRCMR ))
Tc secreted IL-2 and expressed IL-2RTc secreted IL-2 and expressed IL-2R
Finally cells divide, clones proliferation, and secrete effect molecules.Finally cells divide, clones proliferation, and secrete effect molecules.
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Interaction between target cell and TcInteraction between target cell and Tc
ICAM-1 LFA-1
Target cell
(CMs)
MHC-IAg
CD2CD58 Tc(CMRs)
TCR
CD3
B7/BB1 CTLA4
Signal 1
Signal 2
IL-2R
CD8
Cell activation,differentiation , clone proliferation and
secreted effect molecules.
IL-2
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Ag recognitionAg recognition
Tc activationTc activation
Tc killed target cellTc killed target cell
Tc unbindTc unbind Target cell diedTarget cell died
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TH1
Effector Tc
Rest Tc
Target cell
APC
MHCI
MHCII
IL-2 , IL-6 , IFN
TCR
death
Target cell