7.免疫细胞膜分子(一)

免疫细胞膜分子（一）北京大学医学部免疫学系北京大学人类疾病基因研究中心/韩文玲2013年10月11日免疫系统的功能人体免疫系统历经30亿年的进化，形成复杂的精细调控系统，在机体发挥军队和警察的作用。

对外：抵御病源微生物和异己成分；对内：清除病变、衰老细胞。

Stimulating immune responses against microbes by the process of vaccination is the most effective method for protectingindividuals against infections.Worldwide eradication of smallpoxWhat is the immune system?The collection of tissues, cells, and molecules that mediate resistance to infections is called the immune system.Molecules of the immune systemAntibody;Complement;Cytokine;Membrane molecules of immune cells, including TCR, BCR, PRR, HLA, HLDA et al.Cytokines and membrane molecules mediate the interaction between immune cellsEngelhardt, K.R. et al, J Allergy Clin Immunol, 2012. 129 (2): 294-305.Clinical application of cytokines and membrane molecules of immune cellsFoster, D et al. Nature Rev. Drug Discov. 2004, 3, 160–170.免疫细胞膜分子免疫细胞膜分子按其执行的功能，主要可以分为受体、MHC分子、协同刺激分子及粘附分子。

部分免疫细胞膜分子也被称为细胞表面标记（Cell Surface Marker），包括TCR、BCR等。

Human Leukocyte Differentiation Antigen(HLDA)The molecules appear or disappear on the cell surface of human leukocyte during the processes of development, differentiation, maturation, and activation.HLDA Workshop （/ ）CD（Cluster of Differentiation）1、概念：以单克隆抗体鉴定为主，由国际白细胞分化抗原会议将来自不同实验室的单克隆抗体所识别的同一种分化抗原归为同一个分化群，简称CD。

2、组成：CD1-CD363；多为动态表达；T细胞发育: CD4-CD8-; CD4+CD8+; CD4+ or CD8+。

Cluster of Differentiation (CD)The proposed surface molecule is assigned a CD number once two independent antibodies have the same specificity (bind to the molecule);At least one specific mAb if its gene has been cloned.New CDs require definitive molecular identification of the target antigenThere is at least one Workshop-characterized Ab and good molecular data;The antigen is expressed on the surface of cells involved in immune reactions;The Abs react with primary cells (not just transfectants or recombinant protein);The Ab is available.Indication of CDCell populations are usually defined using a …+‟ or a …-‟ symbol to indicate whether a certain cell fraction expresses or lacks a CD molecule.Some cell populations can also be defined as hi, mid or low (alternatively bright, mid or dim), indicating an overall variability in CD expression, particularly when compared to other cells being studied.Human Cell Differentiation Molecules(HCDM)HLDA8: The HLDA Council changed the name of the organization to reflect the broader objectives. The acronym “HLDA” will be succeeded by “HCDM”.(1) To indicate a break with tradition, while retaining the letters “CD”;(2) To maintain the emphasis on molecules of human origin;(3) To extend the focus from leukocytes to other cell types, recognizing that leukocytes do not act alone.(4) To broaden the scope from cell-surface molecules to any molecule whose expression reflects differentiation. (only surface membrane molecules will be given CD numbers, CD1-CD363)Section of CDs（1）T cells: CD2, CD3, CD4, CD8, et al.（2）B cells：CD19, CD20, CD21, et al.（3）Myeloid cells: CD14, CD64, et al.（4）Dendritic cells：CD273, CD274, et al.（5）Adhesion structures: CD11a-CD11c, et al.（6）Cytokine/chemokine receptors.（7）Stem/Progenitor cells：CD133, et al.（8）Stromal cells：CD292, et al.（9）Erythroid cells：CD233-CD242, et al.（10）Platelets：CD36, CD41, CD51, CD61, et al.（11）NK cells：CD16, CD56, et al.（12）Endothelial cells: CD105, CD106 et al.（13）Non-lineage molecules：CD30, CD32, CD46, et al.（14）Carbohydrate structures: CD60a-CD60c, CD75, et al.结构特点1、特点：多为跨膜糖蛋白；部分被糖基磷脂酰肌醇（Glycosyl－phosphatidylinositol，GPI）锚定在细胞膜表面。

N糖基化位点：Asn-X-Thr/Ser中的Asn位点；O糖基化位点：Ser、Thr、Pro占优势序列中的Ser或Thr残基。

2、根据胞膜外区结构分类：IgSF；TNFSF；TNFRSF；整合素；选择素等。

3、根据跨膜区分类I型：一次跨膜，N端：胞外，C端：胞内；II型：一次跨膜，N端：胞内，C端：胞外；III型：多次跨膜（二、三、四、五、六、七）；IV型：多个亚单位组成；V型：多肽以GPI连接于细胞膜的脂质双层中；VI型：一端以GPI连接于细胞膜，另一端为一次或多次跨膜。

胞浆区重要结构域蛋白酪氨酸激酶结构域（Protein Tyrosine Kinase, PTK）；蛋白酪氨酸磷酸酶结构域（Protein Tyrosine Phosphatase, PTP）；死亡结构域（Death Domain, DD）；ITAM/ITIM基序（Immunoreceptor Tyrosine-based Activation Motif/-based Inhibition Motif ）。

ITAM免疫受体酪氨酸活化基序（immunoreceptor tyrosine-based activation motifs, ITAM）：基本结构为YxxL/V，在胞膜相连的PTK作用下，Y发生磷酸化，招募胞浆中具有SH2结构域的其它PTK，启动细胞活化。

ITIM免疫受体酪氨酸抑制基序（immunoreceptor tyrosine-based inhibitory motifs, ITIM）：基本结构为I/VxYxxL，在胞膜相连的PTK 作用下，Y发生磷酸化，招募胞浆中具有SH2结构域的PTP，抑制细胞活化。

Ig超家族分子的结构特点此类分子多为Ig超家族分子；Ig超家族分子：由约100个氨基酸组成、通过链内二硫键形成的具有类似Ig可变区（V区）或稳定区（C区）结构的功能区（domain），并在氨基酸序列上与Ig有一定的同源性的分子。

包括中性粒细胞和单个核吞噬细胞。

中性粒细胞占外周血白细胞总数的60%-70%；寿命2-3天；含初级和次级颗粒，富含蛋白酶；迁移、吞噬能力强。

一、固有免疫细胞膜分子（一）吞噬细胞（Phagocytes）单核吞噬细胞（mononuclear phagocytes）血液中：单核细胞；组织中：巨噬细胞。