免疫复习资料：免疫学PPT整理——至抗原

1、免疫学PPT整理Section 1 introdouction1.Immunity: refers to all mechanisms meknzmz 机制used by the body as protection against environmental agents that are foreign to the body. (to recognize and eliminate foreign substances)2.Agents因子:microorganisms微生物 (viruses, bacteria etc) and their products, foods, chemi

2、cals, pollen, tumor cells, etc.3.Immune system: including immune tissues and organs, immune cells, immune molecules4.Immune response: the coordinated reaction of the molecules and cells in the immune system to a foreign agent.Benefits: protect the host from diseasesDamaging effects: cause tissue dam

3、age5.Immunology is the study of the ways in which the body defends itself from infectious agents and other foreign substances in its environment.6.Pattern recognition receptors (PRR):模式识别受体 7.Pathogen associated molecules patterns(PAMPs）病原相关分子模式:Immune Response Innate immune response natural immune

4、response non-specific immune response Physiological barriers : skin ; mucous membranes Phagocytosis : polymorphonuclear leukocytes (PMN); monocytes/macrophages Natural killer (NK) cell Complement and acute phase proteins Adaptive immune response acquired immune response specific immune responseHumor

5、al immunity: mediated by B cells and defense against extracellular microbes. Cell-mediated immunity: mediated by T cells and defense against intracellular microbes.CharacteristicsCellsMoleculesInnate immunity Responds rapidly No memory No or low specificity Physical barriers Phagocytes Natural kille

6、r cells Humoral factors Complement Acute phase Proteins CytokinesAdaptive immunity Responds Slowly Memory Highly specific T cells B cells Dendritic cells Antibodies Cytokines GranzymesClonal selection theory克隆选择学说By Frank M. Burnet Individual B and T cells possess the ability to make a specific rece

7、ptor (each cell makes a different receptor molecule) Antigen binds to the cell surface receptor and activates the cell Process takes several days. Effector cells and memory cells are produced. Memory cells can thus be activated faster Section 2 Antigen1. Antigen: the substances that induce 引起 a spec

8、ific immune response(recognized by TCR or BCR) and subsequently react with the products of a specific immune response.Properties of Ag：Immunogenicity(免疫原性)：并非都有，recognized by TCR or BCR Immunoreactivity(免疫反应性)：全部抗原都有react with the products of a specific immune responseComplete antigen: both have two

9、 propertiesHapten: (incomplete antigen)A substance that is non-immunogenic but which can react withthe products of a specific immune response. 2. Antigenic determinant (epitope)(抗原表位)：the portion of the antigen that binds specifically with the binding site of an antibody or a receptor on a lymphocyt

10、e；5-15 amino acidsTwo structure: sequential epitope(顺序表位) ；conformational epitope(构象表位)重要T cell epitopeB cell epitopeReceptor TCRBCRMHCnecessarynon-necessaryCharacterlinear short peptidenatural polypeptide polysaccharidesSize812 aa(CD8+T)5 15 aa1217aa(CD4+T)5 7monosaccharidesTypelinear determinant c

11、onformational determinant; lineardeterminantLocationeverywhere of Agsurface of Ag3. Factors influencing immunogenicity抗原分子本身：Chemical Composition；Size（分子量太大，持续刺激）；Chemical Complexity Conformation and accessibility；Physical form；Foreignness（异物性）：不同种属；同一种属不同个体；自身成分改变 宿主特性：Genetic Factors； The age; Wom

12、an and man ; Immunosuppressive agent4. Types of antigens重要TD-Ag （胸腺依赖性抗原）TI-Ag (非胸腺依赖性抗原)TI-1 Ag 抗原表位，丝裂原性质TI-2 Ag 多糖类；重复B表位epitopeB cell epitope ；T cell epitope B cell epitopeImmune responseHumoral immunity cellular immunityHumoral immunity Antibody5:IgM;IgG;IgA;等IgMImmune memorycYNMHC limitationYN

13、Activated B cellsB2B1Xenogenic Ag（异种抗原）Autoantigen（自身抗原）idiotypic Ag(独特型抗原)Allogenic Ag（同种异型抗原）：individuals of a species differ in alleles (are allogeneic) and the antigenic differences will cause an immune response to allograftsc（同种异体）【常见的MHC（HLA）或者红细胞抗原（AB抗原）】Heterophilic Ag (异嗜性抗原) (Forssman anti

14、genc)：A cross-reacting antigen that appears in widely ranging species such as humans and bacteria.Endogenous antigen：（内源性抗原）MHC I pathway, activate CD8Exogenous antigen：（外源性抗原）MHC II pathway, activate CD4c5. Nonspecific immune activators1.Superantigen (SAg) （超抗原）：It stimulate a larger number of T ce

15、lls than normal antigens by reacting both with the MHC presenting molecule and a large subset of T cell receptors. SE(AE)T cell SPAB cell 2.Adjuvant(佐剂)：it is a substance which,when mixed with an immunogen, enhances the immune response against the immunogen. 3. Mitogen（丝裂原）：致使细胞发生有丝分裂 Section 3 Anti

16、bodyAntibody(Ab): Serum srm glycoprotein glakprtin血清糖蛋白which are produced by plasma cells 浆细胞in response to an antigen and binds specifically to particular Ag; antibodies are generally defined in terms of their specific binding to the immunizing antigenImmunoglobulin（免疫球蛋白）Ig：The Immunoglobulins are

17、 globulin which function as Abs or similar to Abs in chemical structureCDR（HVR）: complementarity-determining region or hypervariable regionStructure of ImmunoglobulinMonoclonal antibody(单克隆抗体)：ADCC：Functions of antibody：1.Recognition and binding to antigen（CDR or HVR）2.Activation of complement: IgM,

18、 IgG1,3(经典) IgA,IgE,IgG4(旁路)3.Binding to Fc receptor of cells Opsonization（调理作用）: enhancement of Ag uptake by macrophages (MF)巨噬细胞 Antibody-dependent cell-mediated cytotoxicity (ADCC): NK cells. 直接杀伤靶细胞 Participation in type I hypersensitivity: IgE I型超敏反应4. Passage through the placenta (IgG, CH2) an

19、d mucosa (sIgA)What features distinguish each immunoglobulin class?IgG: (1)单体分子； (2)四个亚类；(3)血清中含量最高(75%Ig)；(4)半衰期最长(2023天)；(5)35岁达成人水平(8.017mg/ml)；(6)可与SPA结合(7）唯一能通过胎盘的IgIgM: 1.IgM is the first Ig synthesized in life and is the first Ig produced in primary immune response. 五聚体2. IgM is a good comple

20、ment fixing Ig and is also a good agglutinating Ig 3. IgM is mIgM of B cells :只表达mIgM是未成熟B细胞的标志IgA:单体型和分泌型(二聚体SIgA) can be transmitted from mother to newborncIgD: is primarily found on naive B cell(初始B细胞-成熟) surfaces where it functions as a receptor for antigen.活化后，消失IgE: is the least common serum I

21、g; Section 4 Complement system1. Definition, basic characteristics and components of complementComplement: A group of serum(血浆) proteins involved in the control of inflammation（炎症）, the activation of phagocytes吞噬细胞 and the lytic细胞溶解酶 attack on cell membranes. This activity is destroyed (inactivated)

22、 by heating serum at 56 for 30 minutes.经活化后具有酶活性，能自我调节的，具有免疫作用的蛋白质。Characteristics：均为糖蛋白血清中含量相对稳定；极不稳定，对温度、酸碱、紫外线照射、机械震荡或某些添加剂敏感。Complement System: consists of a large number of proteins which become enzymes after being activated.Conponents: 来源Liver cells （主要肝细胞） Macrophagesc（巨噬细胞）1. Innate proteins

23、 前端反应 classical pathway:C1q,C1r,C1s,C4,C2 MBL pathway:MBL,MASP alternative pathway: B,D,P terminal pathway:C3,C5,C6,C7,C8,C9补体活化共同组分2. Regulatory ProteinsC1-INH, C4-BP, factor I, factor H, S protein, Sp40/40, decay-accelerating factor (DAF)3. Complement receptorCR1CR5,C3aR,C2aR,C4aR,etc2. Characteri

24、stics of complement activation and the sameness and differences of three complement activation pathways补体活化的特点：激活后才具有酶活性严格的级联反应生物放大效应思可通过三条激活途径发挥生理或病理效应三种补体活化途径 1. Classical pathway -IgG(IgG13) and IgM a suitable Ab bound to antigen (Ag), Ag-Ab complex (IC) C1,C4,C2 and C3，Ca+ and Mg+ cations 过程：C1

25、activation（q-r-s, 钙离子）C4（镁离子，C4b,C4a）C2 activation (镁离子，C2与C4b结合，C2a、C2b, generation of C3 convertase-C4b2a) C3 activation (C3b、C3a,generation of C5 convertase-C4b2a3b) Generation of C5 convertase marks the end of the classical pathway 2. MBL (Lectin) pathwayMBL: 甘露糖结合凝集素 FCN纤维胶原素 识别病原体表面糖结构 MBL act

26、ivate two MBL-associated serine proteases MASP-1 and MASP-2 cleaves C3（C3b）activate the alternative pathway directly cleaves C4,C2 to generate，the C3 convertase (C4b2a) 3. Alternative pathway Activators：bacterial lipopolysaccharides (细菌脂多糖) (endotoxin内毒素), certain complex polysaccharides（某些复杂的多糖）IgA

27、,IgG4,IgEthe presence of suitable activator surfaces从C3开始，C5 convertase: C3bBb3b or C3bnBbcharacters: 1. it can recognize “self” and “non-self” and no factor I and H on the surface of bacterial 2. the amplification loop4.Attack (terminal pathway) the components involved：C5,C6,C7,C8,C9 the membrane a

28、ttack complex(MAC):C5b678(9)n Effects: This complex forms a large channel through the membrane of the target cell, enabling ions and small molecules to diffuse freely across the membrane and causes lysis of cells异同点比较项目 经典途径 MBL途径 旁路途径 激活物 免疫复合物等 Ab:IgM、IgG123细菌表面甘露糖 细菌脂多糖、酵母多糖等凝聚IgA,IgG4 参与的补体成分 C1

29、-9 C2-9、MBL、丝氨酸蛋白酶 （MASP）B因子、D因子、P因子C5-9、 C3所需离子 Ca2+， Mg2+ Mg2+ Mg2+ C3转化酶 C4b2b C4b2b C3bBb C5转化酶 C4b2b3b C4b2b3b C3bBb3b 作用 参与特异性体液免疫效应阶段，在疾病的持续过程中起重要作用。 参与非特异性免疫，可直接激活，在感染早期起重要作用。 参与非特异性免疫，可直接激活，自身放大，在感染早期起重要作用。 相同点：三条途径有共同的末端通路，即形成膜攻击复合物溶解细胞不同点:激活物不同参与的补体成分不同C3，C5转化酶也有不同；作用不同经典：依赖抗体，在感染后期（恢复期）才

30、发挥作用，并参与抵御相同病原体再次入侵。旁路：激活物是细菌、真菌、病毒感染细胞等，自发产生的C3b提供反应表面，正反馈放大效应，无需抗体激活。MBL：激活物质广泛，对经典、旁路途径具有交叉促进作用4. Biological Function of Cplement mediates anti-infectionimmunity (1) complement mediated the lysis of cellsMAC(2) opsonization（调理作用）opsonin: C3b, C4b, iC3b cell: phagocytereceptor: CR1,

31、CR3, CR4 function: enhance phagocytosis (3) inflammatory response（炎症）symptoms: redness, swelling, heat and pain 1.过敏毒素作用：C5a、C3a、C4a可以作用到肥大细胞和嗜碱性粒细胞的细胞膜上，使细胞脱颗粒，释放组胺、白三烯及前列腺素等活性介质，引起类似过敏反应的病理变化2.趋化作用:C5a是中性粒细胞和单核巨噬细胞的趋化因子，可使这些吞噬细胞向炎症部位聚集，加强对病原体的吞噬和消除，同时引起炎症反应。 3.激肽样作用 :C2a、C4a等具有激肽样活性，能增强血管的通透性，引起炎性

32、充血和水肿(4) clearance of IC（免疫粘附功能）C3b(5)其他：elimination of apoptosis cells ：C1q, C3b, iC3bc；参与适应性免疫；与其它血液级联反应系统的相互作用5. Regulation of the Complement System and its significance（了解）1.Self-regulation ：C4b2a, C3bBb, C4b, C3b, C5b2.Control proteins Classical pathway: C1INH, C4bp(C4结合蛋白), I, MCP(膜辅蛋白), DAF(衰

33、变加速因子) Alternative pathway: P, H, I, CR1, DAF,Formation of MAC: C8bp, CD59,SP,SP/40/40 抑制MAC形成 抑制C3、C5转化酶的形成和活性：CR1，DAF,MCP，I仅抑制经典途径的C3、C5转化酶：C4bp仅抑制旁路途径的C3、C5转化酶：H6. Relation between complement system and diseases（了解）临床表现主要相关的缺陷补体成分次要相关的缺陷补体成分遗传性血管神经性水肿C1INH严重顽固性皮肤损害C1q反复发作性细菌感染C3，I因子C1r，C1q免疫复合物性血

34、管炎（包括肾炎）C1q，C1r，C4，C2C3，C5反复发作性革兰氏阳性球菌感染C5，C6，C7，C8系统性红斑狼疮CR1 Section 5 MHC一、MHC：polygenic, polymorphism 人HLA，鼠H-2，表达产物是抗原（分子）MHC：A cluster of genes (complex) on chromosome 6 in humans, encoding cell surface molecules that are polymorphic and that code for antigens causing rapid graft rejection betw

35、een members of a single species that differ at these lociHLA复合体的特征：多基因性，高度多态性，单倍型遗传和连锁不平衡Polymorphism：The phenomenon of having multiple allels at given genetic locus in the populationc 原因：复等位基因很多，共显性；Linkage disequilibrium: the phenomenon that certain MHC alleles at different loci are inherited toge

36、ther more frequently than would be predicted by random assortmentHaplotype：遗传特性，使得孩子只遗传了父母各一个基因（AB,CDAC）二、Structure and Function of HLA molecular1) HLA class I molecules有核细胞 Genes: A, B, C Distribution: every nucleated cell Structure: chain (45kD) 2m (12kD) chromosome 15 闭合 peptide-binding cleft: 1+

37、2 CD8 binding: 3Function: recognize and present the endogenous Ags to CD8+ T cells2) HLA class II molecules抗原提呈细胞胸腺上皮细胞、活化的T细胞 Genes: DR, DQ, DP Distribution: APC (B, DC, M) thymic epithelial cell, activated T cell Structure: chain (35kD) chain (28kD) 开放 peptide-binding cleft: 1+1 CD4 binding: 2 Fun

38、ction: recognize and present the exogenous Ags to CD4+ T cellsc上述2种分子的主要功能是提呈抗原Characteristics of peptide-MHC binding(1) Specificity: special anchor residue. The important point is that peptide binding by a given MHC protein.(2) Flexibility(显示一定的包容性): a series of antigenic peptides with consensus mo

39、tif can be presented by a given MHC molecule, is somewhat selective but mush less specific than antigen binding by a TCR or an Ig.三、Biological function of MHC1.Participate in the adaptive immune response serving as antigen presenting molecules1) T cells recognize both the antigenic peptide and MHC m

40、olecules by TCR TCR识别自身MHC分子提呈的抗原肽2) MHC molecules can present both autoantigens and allogenic MHC molecules3) MHC molecules participate in selection and differentiation of T cells in the thymus.（参与T细胞的选择和分化）4) MHC is the crucial determinant of disease susceptibility in different individuals疾病易感性5)

41、MHC contributes to the genetic heterogeneity of the population（遗传异质性）2.Participate in the innate immunity serving as regulatory molecules1) Classical MHC class III genes encode complement, hereby participating in complement reaction and the pathogenesis of some immune diseases.2) Non-classical HLA c

42、lass I molecules (HLA-E, G) regulate the activity of NK cells.3) Inflammation related genes initiate and control inflammation. They also play a role in stress应激. (such as HSP).四、HLA与临床医学（不太重要）1. HLA与器官移植- HLA-DR对移植排斥最为重要，其次是HLA-B和HLA-AHLA typing（分型）; cross-match（交叉配合）2. HLA分子的异常表达和临床疾病1）恶变细胞表达I类分子下调

43、或缺如，造成免疫逃逸Tumor: class I molecule2）自身免疫性疾病中，原先不表达II类分子的组织细胞诱导表达II类分子，导致免疫应答的异常激活和病理作用。class II molecule3. HLA与疾病的关联某些特定HLA型别的个体易感某一疾病（阳性关联）、对该疾病有较强的抵抗力（阴性关联）与HLA关联的疾病大部分为自身免疫性疾病。Ankylosing spondylitis: B274.HLA与输血反应 - 抗HLA5. HLA与亲子鉴定和法医学利用HLA系统的多基因性和多态性进行亲子鉴定和法医学鉴定。五、Immune function related genes1.

44、Serum complement coded genes（血清补体成分编码基因） HLA class IIIC4B, C4A,Bf, C22. Antigen presenting function related genes （抗原提呈相关基因） HLA class II LMP (proteasome subunit beta type蛋白酶体, psmb):LMP2/7 encoding proteosome beta subunit . Function: process endogenous Ag TAP (transporter associated with Ag process

45、ing加工相关转运物): TAP1, TAP2 Function: transport endogenous Ag peptides Tapasin (TAP associated protein) Function: : participate in the endogenous pathways , help the assemble of the MHCI in ERHLA-DM: DMA and DMB participate in the exogenous pathways, help the peptide肽 binding to the MHCII HLA-DO: negati

46、ve regulation to DM 行使功能的调节蛋白3. Non-classic class I gene (HLA Ib)-HLA-E, HLA-G: inhibit NK cell activityHLA-E： 结合NK细胞和部分CTL细胞表面的C型凝集素受体超家族CD94/NKG2家族.抑制NK 细胞功能；表达于各种组织细胞，在羊膜和滋养层细胞表面高表达。 功能： A.生理状态下NK处于抑制状态 B.母胎耐受 HLA-G：由链和2m组成，有15种等位基因。分布：主要分布于母胎界面绒毛外滋养层细胞，受体：杀伤细胞免疫球蛋白样受体（KIR）家族和白细 胞免疫球蛋白样受体（LIR）家族的

47、某些成员。功能：在母胎耐受中发挥功能4. Inflammation related genesTNF gene family: TNF, LTA, LTB Transcript factor gene family: I-BL, ZNF173 MIC family: MIC A(高多态性), 激活NK 细胞性MIC B Heat shock protein gene family: HSP70额外补充section1.1 Tissues and Organs of the Immune System一、Primary (or central) lymphoid organs定义：the organs in which T and B lymphocytes mature and become competent to respond to antigens. 免疫细胞发生、分化、发育、成熟的场所1.the bone marrow 骨髓HSC造血干