Transcript Immune response and regulation 免疫应答(immune response, Ir)

Immune response and regulation
免疫应答(immune response, Ir)
Body receive stimulation from Ag ，
Specific lymphocytes recognize Ag，they
activate, proliferate and differentiate or
become a state of anergy and apoptosis，
exert biological effect.
Immunological functions
Functions Normal
abnormal
Defense clear pathogen
↑hypersensitivity、
(anti-infection）↓immune deficiency
（ chronic infection ）
homeostasis tolerant to auto-tissue ↑Autoimmune disease
（clear damaged and aged cells）
surveillance clear mutate cell ↓ ontogenesis
（Anti-tumor） (persistent viral infection )
Classification
• Innate immunity （non-specific）
• Acquired immunity （specific）
- Humoral immunity
- Cellular immunity
Classification
• Physiological IR（Immune protection）
Non-self reject
Self tolerant
• Pathological IR（Immune damage）
IR too high hypersensitivity
IR too weak Immune defect
Tolerance terminate  Autoimmune disease
Classification of
specific immunity
（一）体液免疫（humoral immunity）
–To exogenous Ag or soluble
outside of cell
Ag
（二）细胞免疫(cell-mediated immunity)
–To endogenous pathogen ， cellular Ag
（tumor Ag、grafted Ag）.
Place of Ir
Peripheral immune organ (lymph node、
spleen and so on).
Process of Ir
3 stages：
Presenting and recognizing Ag：
Activation、proliferation and differentiation
Effect
Basic process of Ir
Cellular immune response

T recognize Ag and activation

Effect of T cell mediated IR and
mechanism

Biological effect of cellular immunity
3 stages：
①Recognition phase
②Activation，proliferation，differentiation
③Production of effector cells
APC presenting Ag to T cell
Ag +APC
peptide-MH Complex
T cell
Interaction between APC and T cell
• TCR
peptide-MHC
• LFA-1 change conformational structure
• CD4
MHC
CD8
MHC
• Co-stimulatory molecule
一、Requirement for T
recognizing Ag and activation
（一）T cell recognize Ag
* MHC restriction
TCRαβchainre
cognize
MHC on APC surface (MHC
restriction)
Peptide on APC (Epitope of
T cell )
TCR的MHC限制性识别示意图
Molecules involved in T cell
recognition
Recognition phase
1. Take in Ag：
2. Process and present Ag:
3. Interaction between APC and T cell
• Recognition of Ag：
Double recognition: TCR-peptide，
TCR-MHC
Co-receptor:CD4-MHCII, CD8-MHCI
• Binding of co-stimulatory molecules on APC
and T cells：B7-CD28
第二节 Activation，proliferation，
differentiation
Depend on
2 signals and CK
T cell activation for signal requirement
1、2 signals for Th activation
（1）Active signal 1 (Ag)
TCR specifically recognize peptide/MHC
（2） Active signal 2 (binding of costimulatory molecule)
B7-CD28
Adhesion molecules-their ligands
2、CK(IL-2、4、12…)
Signal 1（Ag）：TCR recognize peptide-MHC
Signal 2（Co-stimulator）：binding of ADs
CD4+T
activation
T cell activate
signal 1（Ag
recognition signal）
T cell activate
signal 2（costimulator signal）
Flash
* T acquire
signal ，but
lack signal 2，
anergy and
apoptosis
occur.
* Block or
enhance
active signal
2, can reduce
or increase Ir。
The first signal for T cell activation
TCR
Specifically
recognize
MHC-peptide
Second signal for T cell activation
AD on APC
+
signal
AD on T cell
co-stimulatory
CD28/B7：involve in T cell activation
CTLA4/B7：suppress T cell activation
CK：Promote T cell activation
Proliferation and differentiation of
T cell
Th
effector T
CTL
• Active T
memory T
2. Proliferation and differentiation of CD4+T
Active T
Express variety of CKs and
IL-2+IL-2R
T
IL-12,IFN-g
Th1
cell grow
Th0
IL-4
Th2
receptors
Th divide into Th1 and Th2
Proliferation and differentiation of CD8+T
•Th independent（direct activation）
•Th independent（indirect activation）
IL-2
IL-2
IL-2
Where will Active T go?
• go to effector T；
• go to memory T；
• go to apoptosis.
二、Effect and mechanism of T
cell mediated IR
(一) CD4+Th1 mediate effect (inflammation)
(二) CD8+TC mediate effect (lyses of cell)
Cytotoxicity of CD8+CTL(TC)
MHC restriction recognition of Tc
* TCR recognize peptide/MHC-I on target cell;
requirement for Tc activation
Active signal 1: TCR recognize Ag;
Active signal 2: Co-stimulatory molecule bind
its ligand
CK: APC→ active Th
→CKs（IL-2，IL-6…）
Double signals for TC activation
A
A：lack active
signal 1，TC leave
target cell
B
B：TC recognize infected
cell，With signal 1 and 2，
TC grow ，kill target cell
and leave
The killing mechanism for Tc cell
• The specific recognizing and binding
phase
• The killing phase
（1）active CTL de-granule
release perforin →lysis of target cells
release granzyme→ apoptosis of target cells
（2）Fas-FasL pathway → apoptosis of target cells
（3）Release cytotoxic CKs（IFN-γ，TNFα/β）
CTL release perforin and granzyme to cause
necrosis and apoptosis of target cell
CTL release perforin and form a
channel in target cell membrene
（G=T细胞颗粒，Go=高尔基体，M=线粒体，N=核）
TC express FasL to induce
apoptosis of target cell
FasL
Viral infected targeted
cell
Actuve TC express
FasL AAAAAA
Interaction of FasFasL to induce
apoptosis of
target cell
CTL killing
possess high
Ag-specificity
and MHC
restriction
CTL kill one more target cells
Property：
Specificity、MHC restriction、high efficacy
CD8+TC mediated Ir
T/Target cell
TCR recognize
peptide-MHC-I
Interaction of ADs
signal
signal
1
2
CD4+Th activate
Secret CKs
Resting Tc transform to active Tc
Release perforin and granzyme
Fas、FasL
Death of
target cell
The effect caused by CD4+Th1
Release many kinds of lymphokines，lead to
inflammation
1、Function on M —secret CK
– Activate M :IFN-γ、CD40L
– Induce and attract M: IL-3 、 GM-CSF 、
TNF、MCP-1
迟 发 型 超 敏 反 应 (delayed type
hypersensitivity, DTH) ： caused by
lymphocytes 、 lymphocytes and
monocytes are main cells found in
inflammation site.
Activation
、
proliferation
、
differentiation and migration of
immune cells take too long time,
inflammation occur too late and
maintain longer, referred to DTH.
Active M activated by Th1
Gathering of lymphocytes and
monocytes/M
2、to T cells
promote proliferation of Th1、
CTL，enlarge immune effect
3、to B cells
promote the production of Ab
4、To neutrophill
activate
CD4+TDTH mediated cellular Ir
TDAg
Th1 contact APC
APC take in、process、present
Ag
CD4+Th1 recognize
peptide-MHC-II complex
Active
signal 1
Active
signal 2
Th1 activation
proliferation
CKs
Resting M
Activated M
Secret
inflammatory Cks
DTH
Effect of active
T
(一) CD8+CTL
mediate
cytotoxicity
(二) CD4+Th1
mediate DTH
(三)CD4+Th2
assist B to
produce Ab
The process of Immune response
三、Biological effect of cellular
immunity
(一) Killing endogenous microorganism → antiinfection immunity;
(二) Killing tumor cell → anti-tumor immunity;
(三) Immune damage
killing grafted cells → graft rejection reaction
killing auto cells and tissue → AID。
DTH
Review Questions
• Describe the process of IR mediated by
CD8+T.简述CD8+T细胞介导的免疫应答过
程。
• Describe the process of CD4+T activation简
述CD4+T细胞的活化过程。
• Describe the interaction of APC and Th简
述APC-Th细胞是如何相互作用的。