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

Physicochemical properties of antigen dosage Inoculate ways As the antigen concentration drops, relatively the intensity of immune response fall off. Regulation of antigen

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-Ab- FcγRIIb 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 * immune adherent facilitate to eliminate IC opsonization

6. CKs and Immunoregulation * 1.CKs regulate development and germination of immune cells * 2.Bidirectional immunoregulation of CKs

Myeloid stem cell lymphoid

Positive regulation : Negative 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 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 T细胞亚群与细胞因子 IL-12 IL-4

Section 3 Role of cells

Immune regulation of Th1/Th2 T cell and immunoregulation

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 autoimmune disease Th2 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

缺乏 B7 肿瘤逃逸

Role of regulatory receptor on the surface of immune cells (1) Activated receptor （ positive ） ( ITAM ) (2) Inhibitory receptor （ negative ） ( ITIM )

免疫细胞 激活性受体 抑制性受体 B cell BCR/Ig  /  Fc  R Ⅱ B T cell TCR/CD3 CTLA-4, KIR NK CD16, DAP12 KIR,CD94/NKG2 mast cell Fc  R Ⅰ Fc  R Ⅱ B, gp49B1 免疫细胞的激活性受体和抑制性受体

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

（ 1 ） idiotype Ig, TCR, BCR V region antigenic specificity ， can induce production of anti-idiotype (Ab2 ）。 Role of the idiotypic network

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

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 。 regulation of idiotype － anti-idiotype

antibody Anti-idiotype vaccine epitope Antibody with epitope binding site Virus 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。

antibody Anti-idiotype vaccine Make antibody against antibody idiotype Anti- idiotype antibody Anti-idiotype antibody mimics the epitope

Anti-anti-idiotype antibody Anti-idiotype antibody Use anti-idiotype antibody as injectable vaccine Antibody to anti-idiotype antibody Binds and neutralizes virus Anti-idiotype antibody Anti-anti-idiotype antibody Use as vaccine

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