Download 08Immune response

Chapter 11. Immune response (1)
I. Introduction
II. Antibody-mediated Humoral
Immunity
I.
Introduction
1. Concept of Immune Response
2. Types of Immune Response
3. Process of Immune Response
1. Immune response
The immune system of body is able to
recognize subtle chemical differences that
distinguish one foreign pathogen from another. At
the same time, the system is able to discriminate
between foreign molecules and the body’s own
cells and proteins. Once a foreign organism is
recognized, the immune system eliminate or
neutralize the organism, finally.
2. Types of Immune Response
Ag
selection Immune
system:
activation
“Self”Ag
“non-self”Ag
Autoimmunity
Autoimmune Tolerance
HI / CMI
Immune Tolerance
Hypersensitivity Reaction
II. Antibody-mediated Humoral Immunity
concept of HI ，simple process of HI
1. Common rule of Ab production
2. Interaction between immune cells in
process of producing Ab
3. Immune Memory
4. Effect of Humoral Immunity
Humoral Immunity，HI
Humoral immunity is mediated by
antibodies of various different classes;
which Ab are produced by cells of the B
cell lineage in response to stimulation by
Ag.
Simple process of HI:
1、TD—Ag
APC
TH
BL2
THm
2、TI—Ag
BL1
BLm
Mature B cell
Plasma cells
Ab
HI
1.Common rule of Ab production
a. The regularity of Ig production in phylogenic
evolution and development,and ontogenesis.
b. The regularity of Ab production in the primary
and secondary response。
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.
Primary IR
Antigen
The first contact of an
individual with an Ag
latent period long (1W，2-3W)
slow of Ab production
Ab Conc.
low in serum
Maintain Time short,decrease quickly
type of Ig
IgM
Affinity
lower
present of Ag M, DC
Secondary IR
A second injection of the
same Ag
short (1-3day)
high in serum
longer
IgG
higher
B cell
Ig
IgM
IgG
Concentration of Ig
Latent period
10day
Primary stimulation of Ag
3day
Secondary stimulation of Ag
2.
Interaction between immune cells
in the process of producing Ab
TD—Ag response
a. Interaction between M and Th cells
* M presented Ag
*Interaction between cells
b. Interaction between Th cell and B cells
* B cell presented Ag * Interaction between cells
c. Interaction between M and B cells
TI—Ag response
B cell : response of TI—Ag
• Ags are ingested, processed, presented
by M (primary response)



Ingestion：endocytosis, passive adhesion。
Processing：lysosomal enzymes condense
and degrade Ag,and combine to self-MHCII
molecules.
Presentation：These complexes of peptide
and MHC molecules are transported to the
surface of the cell where they are recognized
by the T-cell receptor.
Exogenous Ag
endocytosis
degradation
TCR
CD4
expression
MHCII
endosome
combination
Transportation
APC
Virus（endogenous Ag）
DNA
transcription
mRNA
translation
Pr
degradation
CD8
CTL
TCR
MHCI
Target cell
• Interaction between M and Th cells
（primary response）
Double signal hypothesis of Th cell activation ：
The first signal ：
Th: TCR/CD3——APC: Ag-MHCII complexes
at the same time, TH: CD4——APC: The 2,2 domain of MHCII
The second signal ：
APC: B7/BB1（CM）——TH: CD28（CMR）
TH secreted IL-2 and expressed IL-2R
Finally cells divide, clones proliferation, and produce a kind of CK.
APC
(CMs)
CD58
B7/BB1
TH
(CMRs)
CD2
CD28
CTLA4
CD3
Ag
MHC-II
Signal 1
TCR
CD4
ICAM-1
VCAM-1
Signal 2
LFA-1
VLA-4
IL-2
IL-2R
Interaction between APC and Th cell
Cell activation,（CK）
cell differentiation and
clone proliferation
APC
MHC-Ag
TCR/CD3
Signal 1
APC
B7/BB1
CD28
Signal 2
Signal 1
TH
IL-2 production
clone proliferation
Signal 2
TH
not IL-2 production
clone anergy
Suppressive immune response ：
Hypersensitivity Disease
Autoimmunity Disease
Graft rejection responses
Ag
APC
MHC
TCR
TH
inactivation
B7
CD28
Anti-B7Ab
CTLA4 Ig
Anti-CD28
Interdiction of co-stimulatory signals
Enhancing immune response：
Tumor immunity treatment
Ag
MHC
TCR
Tumor cell
CTL
signal1
CTL activated
Killer tumor cell
signal2
CD28
Ag
Tumor cell
MHC
TCR
CTL
signal1
signal2
B7
CD28
Transfection B7gene
CTL activated
Killer tumor cell
• Interaction between Th and B cells
（secondary response）
Th cell activation： Double signal hypothesis
Signal 1：Th: TCR/CD3——B cell: Ag-MHCII complexes
Th: CD4——B cell: The 2,2 domain of MHCII
Signal 2：Th: CD28 molecule ——B cell: B7 molecule.
B cell activation： Double signal hypothesis
Signal 1：B cell: BCR--Ag，Ig,Ig transfer activation signal 1
Signal 2：B cell: CD40——Th: CD40L
Th and B cell inducing signal of activation each other，Th produced IL-4,5,6.
B cell is helped at Th cell, finally B cell proliferated and differentiated
turn into the plasma cells of producing a kink of Igs.
B cell
ICAM-1
Ag
T cell
LFA-1
CD3
B7
SIg
Signal 2
CD28
CD3
Ag process
MHC-II
present
1
Signal 1
TCR
CD4
2
CD40
CD40L
singal
LFA-1
ICAM-1
CKR
B cell activation
CK
Th activation
Interaction between B cell and T cell
M
M
process
present
MHC-II
TCR
Ag
ingestion
IL-2，4，5，6
IL-1
PC
Activate Th
ingestion
TCR
MHC-II
B
process
Bm
present
Activate B
IgG
IgA
IgE
B
B B
proliferation
IgM
differentiation
Bm Bm
Bm Bm
c. Interaction between M and B cells
signal
signal
B cell
B cell
I type: TI—Ag is
II type: multiple repeat-lined
antigenic determinant makes
receptor linkage
polyclonal stimulator
TI-Ag response
3. Immune Memory-Secondary response
Characteristic :
a. Immune memory cells
b. Class switching of Ig
c. Affinity Maturation of Ab
Characteristic：
* 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
4. Effect of Humoral Immunity
Neutralization of Ab
 Opsonization of Ab
 Complement dependent cell-mediated
cytotoxicity,CDC
 Antibody dependent cell-mediated
cytotoxicity,ADCC
 Immune regulation of Ab

FcrR
Bacteria
Anti-bacteria Ab
Boost up lick up action
Opsonization of Ab
M
Surface Ag
FcrR
IgG
Target cell
M , NK
Dissolution of target cell
Antibody-dependent cell-mediated cytotoxicity, ADCC
Chapter12. Immune response (2)
I. Introduction
II. CD4 T-mediated immunity
III.CD8 T-mediated immunity
I. Introduction
1. Concept, Simple process
2. Major functions of CMI
Simple process:
secondary
TDTH
TD-Ag
Immune system
Tc
CK
Cytotocixity
2. Major Functions of CMI






Delayed Type Hypersensitivity, DTH
Intracellular Anti-infection
Anti-tumor
Transplantation rejection reaction
Graft Versus Host Reaction, GVHR
Autoimmunity diseases
II. CD4 T-mediated immunity
1. Activation of CD4 T cells
2. Formation of DTH inflammation
* CK production * Function of M
• Activation of CD4 T cells
Double signal hypothesis of CD4 T cell activation ：
The first signal ：
Th: TCR/CD3——APC: Ag-MHCII complexes
at the same time, TH: CD4——APC: The 2,2 domain of MHCII
The second signal ：
APC: B7/BB1（CM）——TH: CD28（CMR）
TH secreted IL-2 and expressed IL-2R
Finally cells divide, clones proliferation, and produce a kind of CK.
IL-2R
APC
(CMs)
CD2
CD58
B7/BB1
MHC-II
TH
(CMRs)
CD28
CTLA4
Ag
CD3
TCR
Signal1
CD4
ICAM-1
VCAM-1
Signal 2
LFA-1
VLA-4
IL-2
IL-2R
Cell activation,（CK）
cell differentiation and
clone proliferation
T
APC
T
IL-2
T
T
T
T
APC
T
APC
T
TNF
IFNr
M
rest
CK of DTH reaction
M
activation
III.CD8 T-mediated immunity
1. Activation ofCD8 T cells
2. Mechanisms of Tc killing
target cells
a. Perforin
b. Granzymes
c. TNF associated proteins
• Activation of CD8 T cells
Double signal hypothesis of CD8 T cell activation ：
The first signal ：
Tc: TCR/CD3——Target cell: Ag-MHC-I complexes
at the same time, Tc: CD4——Target cell: The 3 domain of MHC-I
The second signal ：
Target cell: B7/BB1（CM）——Tc: CD28（CMR）
Tc secreted IL-2 and expressed IL-2R
Finally cells divide, clones proliferation, and secrete effect molecules.
Target cell
(CMs)
CD58
CD2
B7/BB1 CTLA4
CD3
Tc
(CMRs)
Ag
TCR
MHC-I
Signal 1
CD8
ICAM-1
LFA-1
Signal 2
IL-2R
IL-2
Cell activation,
differentiation , clone
proliferation and
Interaction between target cell and Tc secreted effect
molecules.
Ag recognition
Tc activation
Tc killed target cell
Tc unbind
Target cell died
TCR
Rest Tc
Target cell
MHCI
APC
IL-2，IL-6，IFN
TH1
MHCII
death
Effector Tc
Target cell