免疫复习资料：免疫 自己整理版 名解

1、1. Immunology is the study of the ways in which the body defends itself from infectious agents and other foreign substances in its environment. Immunity: refers to all mechanisms used by the body as protection against environmental agents that are foreign to the body. (to recognize and eliminate for

2、eign substances) 2.Innate immunity It refers to any inborn immunity that is already present the first time a pathogen is encountered. 3.Adaptive immune response The T cells and B cells in the body recognize the antigen and, in turn, become activated. The activated lymphocytes then proliferate and ca

3、rry out their specific effector functions 4.Humoral immunity: mediated by B cells and defense against extracellular microbes. 5.Cell-mediated immunity: mediated by T cells and defense against intracellular microbes. The innate and adaptive immune response Introduction Characteristics Cells Molecules

4、 Innate immunity Responds rapidly No memory No or low specificity Physical barriers Phagocytes (PMNs and macrophages) Natural killer cells Humoral factors Complement Acute phase Proteins Cytokines Adaptive immunity Responds Slowly Memory Highly specific T cells B cells Dendritic cells Antibodies Cyt

5、okines Granzymes Clonal selection theory 全身的免疫细胞是由众多识别不同抗原的细胞克隆所组成，同一种克隆细胞表达相同的特异性受体，淋巴细胞识别抗原的多样性是机体接触抗原前就有的，是生物在长期进化过程中形成的。抗原进入机体只是从免疫细胞中找出能识别这种抗原的淋巴细胞克隆，活化，增殖，扩增出许多具有相同特异性的子代细胞，产生大量特异性抗体清除入侵的抗原。 日 T Lymphocytes TCR: T-cell antigen receptor TCRab+ 95% TCRgd+ 15% 1. Cytotoxic T cells (CTL) 2. helper

6、 T cells: Th1, Th2, Th17 3. Regulatory T cells (Treg) and suppressor T cells (Ts) Th1 巨噬细胞活化 IgGTh2 肥大 嗜酸 IgEBone marrow1.the place in which proliferation of HSC takes place 2.the place in which development and maturation of B cells occur The lymphoid progenitor cells are transported by circulating

7、blood to the thymus and differentiate into functional T lymphocytes The thymus 1. Cells: thymic stromal cells (TSC) epithelial cells, monocytes (macrophage), TDC thymocytes T cell (ab+) 2. Structure: cortex-immature thymocytes medulla-mature thymocytes Mf, TDC 3. Function: It is the site of T cell m

8、aturation/selection; It determines the specificity of the TCR expressed on the T cells released to periphery The lymph node 1.Human:2-10mm in diameter 2.round and kidney shaped 3.Consists of cortex (B-cell area) paracortex (T-cell area) central medulla (B-cell area) The spleen 180-250g germinal cent

9、er (B) 1. the white pulp periarterial lymphatic sheath (T) the red pulp (B) 2. function: destroy the Ag, aged platelets immune response Lymphocyte recirculation 1.Lymphocytes leave the blood via high-walled endothelium of the post-capillary venules. 2.Lymphocyte trafficking exposes antigen to a larg

10、e number of lymphocytes. Lymphocyte homing血液中淋巴细胞选择性趋向迁移并定居在外周免疫淋巴器官的特定组织的过程Lymphocyte recirculation定居在外周免疫器官的淋巴细胞，由输出淋巴管进入血液循环，经血液循环到达外周淋巴器官后，穿过HEV，重新分布于全身淋巴器官和组织的过程Double negative cells (DN) CD4-CD8-; CD2+, CD5+, cytoplasmic CD3+ nDouble positive cells (DP) CD4+CD8+, CD1+, CD3+, gdTCRlow, abTCRlow

11、 nMature T cells (single positive T cells) CD4+ or CD8+, CD2+, CD3+, TCR+ 4. Positive and negative selection Positive selection: DP cells that bind, with moderate affinity, to MHC-Ag on thymic stroma cells survive-MHC restriction MHC I-CD8+ T cells MHC II-CD4+ T cells Negative selection: Cells that

12、bind to MHC-Ag on thymic stroma cells (or auto-reactive T cells, ART) with high affinity will undergo apoptosis Formation of central immune tolerance 1. CD4+ helper T cells (Th): Th0:Th cells that secrete broad spectrum of cytokines at low level. Th1: produce IL-2 and IFN-, but not IL-4. They are ch

13、iefly responsible for cell-mediated immune responses, but can also help B cells to produce IgG2a, but not much IgG1 or IgE; Th2: secrete IL-4, 5, 10, 13, but not IL-2 and IFN-, are very efficient helper cells for production of antibody, especially of IgG1 and IgE ; Th17: secrete IL-17 and IL-21, med

14、iate innate immunity and inflammation, especially autoimmune disease. Key point Immune tolerance Immune tolerance or Immunological tolerance is a state of unresponsiveness that is specific for a particular antigen; it is induced by prior exposure to that antigen.Tolerogen 耐受原B cell central tolerance

15、Clonal deletion During maturation of B lymphocytes in bone marrow , immature lymphocytes that recognize membrane-bound self-antigen with high affinity are deleted by apoptosisClonal anergy During maturation of B lymphocytes in bone marrow , immature lymphocytes that recognize soluble self-antigen ar

16、e not deleted but are inactivated Receptor editing: light chain rearrangementT cell central tolerance1 T cell Clonal deletion (apoptotic cell death) During maturation of T lymphocytes in the thymus, immature T lymphocytes that recognize ubiquitous self-antigen with high affinity are deleted by mecha

17、nism of apoptosis2 Tissue-restrictive genes expressed by MECsAIRE(autoimmuneregulator): transcription factor that enables ectopic expression in the thymus of genes usually considered tissue-specificImmunoregulation免疫应答过程中免疫细胞间、免疫分子与免疫细胞间以及免疫系统与机体其他系统间相互作用，感知机体免疫应答并实施调控，从而维持机体的内环境稳态。Immune responses

18、are tightly regulated by complex interaction of immune cells & immune molecules, which can sense and control immune responses, thereby maintain the homeostasis of internal environment. Regulation by Inhibitory receptors B cell, mast cell: FcgRIIB，PIRB Cross-linking immune complex or anti-idiotype an

19、tibody with BCR T cell: CTLA-4, PD-1 CTLA-4 and PD-1 transmit signals that inhibit lymphocyte activation, providing a pathway of classical feedback inhibition. NK, CTL: KIR，CD94/NKG2A ANTIGEN 抗原Antigen (Ag) the substances that are recognized by TCR/BCR or antibody and induce a specific immune respon

20、se.Epitope 抗原分子中决定免疫应答特异性的特殊化学基团，是抗原与BCRTCR&抗体特异性结合的最小结构和功能单位。Hapten 小分子物质单独不能诱导免疫应答，既没有免疫原性，但是与carrier结合或交联后获得免疫原性，诱导免疫应答。单独可以和免疫应答产物结合，既有免疫反应性。 抗原Antigen (Ag) the substances that are recognized by TCR/BCR or antibody and induce a specific immune response. hapten + carrier complete Ag T cell epitop

21、e B cell epitopeReceptor TCR BCRAPC,MHC necessary unnecessary Character linear short natural polypeptide peptide polysaccharides linear determinant conformational determinant ; linear determinant Size 8-10aa (CD4+T) 5-15aa 2,9 anchor residue 13-17aa(CD8+T)Location Ag surface of Ag TD-Ag胸腺依赖性抗原Thymus

22、 -dependent antigens are those that do not directly stimulate the production of antibody without the help of T cells.B cell epitope T cell epitope Humoral immunity and cellular immunityAntibody: five typesImmune memory Proteins are thymus -dependent antigens.TI-Ag胸腺非依赖性抗原 Thymus -independent antigen

23、s are antigens which can directly stimulate the B cells to produce antibody without the requirement for T cell help In general. only B cell epitope Humoral immunityAntibody :IgMNo Immune memory polysaccharides are TI- antigens. 异嗜性抗原Heterophilic Ag (Forssman antigen) -A cross-reacting antigen that a

24、ppears in widely ranging species such as humans and bacteria. 人、动物、微生物等不同种属之间的共同抗原Xenogenic Ag异种抗原Allogenic Ag同种异型抗原idiotypic Ag独特型抗原 - The combined antigenic determinants (idiotopes) found on antibodies of an individual that are directed at a particular antigen; such antigenic determinants are foun

25、d only in the variable region. 抗体可变区中独特的氨基酸序列所组成的抗原表位称作独特性抗原。Endogenous antigen APC内合成，细胞质内加工处理成抗原肽，MHC 1 类结合 CD8+细胞TCR识别Exogenous antigen 外来抗原 胞吞、胞饮、受体介导进入APC降解 MHC2 CD4+ TCR 识别Adjuvant 预先或者和抗原同时注入体内，可增强机体对抗原的免疫应答或者改变免疫应答反应类型的非特异性免疫增强性物质。it is a substance which, when mixed with an antigen, enhances

26、 the immune response against the antigen. The use of adjuvants, however, is often hampered by undesirable side effects such as fever and inflammation.生物性无机化合物人工合成物有机物脂质体FCA（弗氏完全佐剂）, FIA （弗氏不完全佐剂）, BCG, CP, LPS, CpG。抗体B细胞接受抗原刺激后增殖分化为浆细胞所产生的糖蛋白。主要存在于血清等体液中，能与相应抗原特异性结合，显示免疫功能。主要存在于区。（了解）同种型isotype 指同种抗

27、体分子中的抗原表位，存在于Ab的C区。同种异型 allotype指同种但不同个体中抗体的免疫原性，存在于Ig C区。独特型（idiotype, Id）指同一个体来源抗体的不同免疫原性，存在于CDR区。可刺激产生抗独特型抗体（anti-idiotype antibody, AId）IG的生物学功能Fab功能中和毒素、阻断病原入侵、清除病原微生物等。B细胞的抗原识别受体（BCR）特异性识别抗原分子；有利于抗原或抗体的监测和功能的判断。Fc的功能（一）激活补体（二）结合Fc段受体 1. 调理作用 opsonization 2. ADCC 3. 介导型超敏反应（3） 穿过胎盘和黏膜 iGg单克隆抗体（

28、monoclonal antibody, mAb）针对单一抗原表位的高度均一的特异性Ig。Complement (C) 补体 蛋白质 溶解细胞 不耐热A group of serum proteins involved in the control of inflammation, the activation of phagocytes噬菌细胞 and the lytic细胞溶素 attack on cell membranes. This activity is destroyed (inactivated) by heating serum at 56C for 30 minutes .

29、补体来源：肝细胞、单核巨嗜细胞、上皮细胞Classical pathway IC（与抗原结合的igG IgM） C1q r s 、C4 C2 C3 C56789Alternative pathway 内毒素、细菌、葡聚糖、酵母多糖 C3 B D （备解素P稳定C3转化酶） C56789MBL pathway MBL识别病原体表面糖结构 细菌？MASP12MASP2 classical MASP1 alternative c56789MBL对classical &alternative具有交叉促进作用Cytokine 免疫细胞及组织细胞分泌的在细胞间发挥互相调控作用的一类小分子可溶性多肽蛋白，通

30、过结合相应受体调节细胞生长分化和效应，调控免疫应答。Cytokines are low-molecular weightregulatory proteins （ glycoproteins)secreted by white blood cells andvarious other cells in the body inresponse to a number of stimuli.These proteins mediate and regulateimmune and inflammatory reactions.细胞因子的property基本特征小分子蛋白质可溶性高效性 低浓度下即有

31、生物活性通过结合细胞表面受体发挥生物学效应可诱导产生半衰期短效应范围小，绝大多数为近距离发挥作用作用方式自分泌 autocrine旁分泌 paracrine内分泌 endocrine 循环系统功能特点多效重叠协同拮抗网络1.1 Cytokine secretion is a brief, self-limited event;1.2 The actions of cytokines are often pleiotropic多效 andredundant重叠;1.3 Cytokines often influence the synthesis and actionsof other cyto

32、kines ;1.4. Cytokine actions may be local and systemic ;1.5. Cytokines initiate their actions by binding tospecific membrane receptors on target cells;1.6. The cellular responses to most cytokines consist ofchanges in gene expression in target cells, resultingin the expression of new functions in th

33、e targetCellsChemokine 多种细胞分泌的对不同细胞具有趋化作用的细胞因子family of small cytokines, or proteinssecreted by cells. Their name is derivedfrom their ability to induce directedchemotaxis in nearby responsive cells; theyare chemotactic cytokines.Colony-stimulating factor 能够刺激多能造血干细胞和不同分化阶段的造血祖细胞分化、增殖的细胞因子。are secreted glycoproteins whichbind to receptor proteins on the surfaces of hemopoietic stem cellsand thereby activate intracellular