Medical immunology
Chapter 14
Immunoregulation
教学大纲
• 熟悉T细胞亚群及其相互调节机制、独特
性网络和抗原内影象概念
• 了解抗原、抗体、抗原抗体复合物、补
体以及ITAM/ITIM对免疫应答的调节作
用
• 了解免疫应答的基因调控、凋亡机制对
免疫应答的调节以及整体和群体水平的
免疫调节
免疫调节（immunoregulation):
the body control persistent and
intensity of immune response by positive or
negative regulators in order to maintain the
balance of the whole body.
functions：
1. enhance immunity ,eliminate
foreign antigens ；
2. diminish harm to self tissues。
Section 1
Discription
I . Sensing of immune system
precondition of immunoregulation
II . Sensing signals by immune system
& Quantitative change and qualitative
alteration of immune molecule
*Antigen doses
*Antibody concentration
*Proporation between Ag and Ab
& Quantitative change of Immune cells
clone
& Affinity between ligand and receptor
III . Mechanism of negative regulation play
a major role
& negative regulation is critical for
maintaining self homeostasis
* can maintain self tolerance
* can maintain proper Ir
Ⅳ . immune intervention :artificial
Section 2 molecule regulate
immune response
• I . Role of antigen
Regulation of antigen
•Physicochemical properties of antigen
•dosage
•Inoculate ways
As the antigen concentration drops, relatively the
intensity of immune response fall off.

结构相似的不同抗原之间竞争性调节
Regulation of antibody
& . Organism sense and adjust
concentration of Ab
& . Ab mediate immunoregulation
* block antigen ：Ab bind competitively
specific Ag epitope with BCR or TCR ,
block soluble Ag or membrane Ag
Mediate inhibitory receptor cross-link ：
•Receptor cross-link：BCR-Ag-AbFcγRIIb
Fc region of Ab
FcγRIIb
Ag
BCR
Antibody dependent B cell suppression
Ⅳ.Role of complement
& regulation of complement activation
* complement active fragment
inactivate spontaneously
* complement regulatory protein:negative
&
complement active fragment mediate
immunoregulation
* C3b、C4b、iC3b
bind with Mφ
opsonization
* immune adherent
facilitate to eliminate IC
6. CKs and
Immunoregulation
* 1.CKs regulate development and
germination of immune cells
* 2.Bidirectional immunoregulation of
CKs
lymphoid
Myeloid
stem cell
• Positive regulation :
IFN-γ、TNF-α : promote expression of MHC
on APC
IL-2、IL-4、IL-5、IL-6：promote T、B cell
activation 、proliferation、differentiation
IL-12、TNF-α：activate CTL
• Negative regulation:
Il-10、TGF-α：inhibit Mφ、T cell ,
reduce release of CKs
• CKs regulate differentiation of Th cell
and affect type of Ir
T
细
胞
亚
群
与
细
胞
因
子
IL-12
IL-4
Section 3 Role of cells
T cell and immunoregulation
Immune regulation of Th1/Th2
Relation between CKs and differentiation
of Th0 into Th1 and Th2 subsets
+
–
* Th1和Th2互为抑制细胞，
从而调节机体的细胞免疫
和体液免疫应答；
免 疫 偏 离 immune deviation
免疫偏离（immune deviation）:Th1或Th2细胞的优先活化而导致不同类
型免疫应答及其效应呈优势的现象。
Immune deviation
• Th1
• Th2
autoimmune disease
type – I hypersensitivity
Graves disease，SLE
Suppressor T cell
• CD4+ CD25+ regulatory T cells
• Secrete CKs to inhibit function of effect T
cells
• Also can affect the activation and
function of innate immune cells
• be used for immunotherapy of chronic
inflammatory or autoimmune disease
Apoptosis in immune response
• CTL and NK exploit apoptosis as one
mechanism for killing target cells that
express Fas
• AICD (activation induced cell death)
Th cells express both Fas and FasL , may
kill either themselves or one another
lack of Fas/FasL,
tumor or AID
regulation of cell apoptosis
negative
* FasL/Fas pathway mediated AICD
activated T cell clone apoptosis.
activated induced lymphocyte clonal apoptosis
Functions of AICD：
Eliminate activated T/B cell clone，terminate immune
response and keep immune tolerance。
• Role of regulatory receptor on the
immune cell surface
*co-signal molecule on T cell surface
CD28
B7 co-stimulator ITAM
CTLA-4
B7 co-inhibitory molecule
ITIM
肿瘤逃逸
缺乏B7
Role of regulatory receptor
on the surface of immune cells
(1) Activated receptor（positive ）
( ITAM )
(2) Inhibitory receptor（negative ）
( ITIM )
免疫细胞的激活性受体和抑制性受体
免疫细胞
激活性受体
抑制性受体
B cell
BCR/Iga/b
FcgRⅡB
T cell
TCR/CD3
CTLA-4, KIR
NK
CD16, DAP12
KIR,CD94/NKG2
mast cell
FceRⅠ
FcgRⅡB, gp49B1
T/B细胞激活性受体的调节作用
T/B细胞抑制性受体的调节作用
role of NK cell
activated receptor and inhibitory receptor
Role of the idiotypic network
（1）idiotype
Ig, TCR, BCR V region antigenic specificity，
can induce production of antiidiotype (Ab2）。
The unique V-region amino acid
sequences of immunoglobulin
独特型和抗独特型抗体(抗体模型)
（2）anti-idiotype
Ab2α：block the binding of antigen and
BCR、TCR or Ig（Ab1）,inhibit
activation of T/B cell (suppression)
Ab2β：V region have similar shape with
antigen，simulate antigen，promote T、
B activation and proliferation .So it is
called internal image of antigen .
(stimulation)
（3） regulation of idiotype－anti-idiotype
network
Ab3  bind Ag
↑
Ab2-β  bind B(T)CR  B/T cell activated
↑
Ag  Ab1（idiotype）
↓
Ab2-α block antigen binding  inhibit B/T
activation
•anti-BCR idiotype Ab
→mediate cross-link between
BCR and FcR of B cell
→produce inhibitory signal
→inhibit B cell proliferation and
antibody secretion
regulation of idiotype－anti-idiotype
• positive:
internal image of antigen can simulate antigen,
enhance and amplify Ir。(act as vaccine)。
• negative：
Terminate Ir in proper time，participate in
formation and maintenance of immune
tolerance。
研制抗独特型疫苗：适于某些不易获得其抗原成分
的病原体，或难以精确分离纯化抗原的肿瘤组分。
Anti-idiotype vaccine
Virus
epitope
antibody
Antibody
with
epitope
binding site
Anti-idiotype vaccine
Antiidiotype
antibody
antibody
Make antibody
against antibody
idiotype
Anti-idiotype
antibody mimics
the epitope
Anti-idiotype antibody
Use anti-idiotype antibody as
injectable vaccine
Use as
vaccine
Anti-idiotype
antibody
Binds and
neutralizes virus
Anti-anti-idiotype
antibody
Anti-anti-idiotype
antibody
Antibody to anti-idiotype antibody
Anti-anti-idiotype
antibody
regulation of individual level
（neuroendocrine immune system
regulation）
1.Role of neuroendocrine system：
glucocorticoids、sex hormones :inhibit Ir；
Growth hormone、thyroxine : augment Ir。
2.Immune system influence
neuroendocrine system：
Immune cells secret IL-2 :inhibit
release of Ach；TNF-α enhance
nerve cell expression enkephalins
Lymphocyte produce ACTH :increase
release of glucocorticoids。
p170
思 考 题
• Describe immune regulation of
molecules.试述分子水平的免疫调节；
• Describe immune regulation of cells
试述细胞水平的免疫调节；
• Describe immune regulation of
idiotype anti-idiotype network.试述
独特型-抗独特型网络的调节